Record #1 %%%% TTL: Economic outcomes associated with the use of risperidone in a naturalistic group practice setting AUT: Nightengale B S, Garrett L, Waugh S, Lawrence B J, Andrus J XSO: American Journal of Managed Care XYR: 1998 VOL: 4(3) PAG: 360-366 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: Risperidone versus haloperidol in a naturalistic setting. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: Patients over the age of 18 years suffering from either schizophrenia, schizoaffective disorder, or major depression with psychotic features. XSG: The practice setting was primary care. The economic analysis was carried out by Applied Health Outcomes, Inc, Oklahoma City, USA. XDD: Both prospective and retrospective effectiveness and resource data were obtained between June 1994 and November 1996. No prices were stated. XDR: Discounting was not applied due to the short period of analysis. Direct costs included medication, inpatient, day hospital utilisation, and clinician costs (source: local charge rates/billing data). No price year was stated. XMB: Economic benefits were measured in terms of resource utilisation comparisons and resulting cost comparisons. The perspective used was that of the payer. XSD: This was a cohort study. A matched control group was used within a longitudinal design. XSS: Effectiveness data around risperidone and haloperidol consuming subjects was derived from a single pilot project. OI: The authors made some reference to findings from other studies in comparison with their own results. The authors did not appear to have presented their results selectively. The authors' conclusions reflect the scope of the analysis. The authors reported that the sample sizes used within the analysis were another limitation on the conclusions drawn. SCO: The selection of haloperidol and risperidone as comparators within the study was justified and, as a reflection of current practice, was appropriate for the study question. VB: Appropriate statistical analyses were carried out, although the within-subject variances cannot be assumed to be equal in the regression analysis as the number of observations per patient were not the same. The study sample was representative of the study population and patient groups appeared to be comparable at analysis, although only age, gender and initial GAF scores were shown. Inadequate health benefits were used in the economic analysis with costs replacing them. The study was of cost-consequences design. VC: All categories of cost relevant to the perspective adopted were included in the analysis. Limitations of the cost analysis included the points that costs and quantities were not reported separately, charges were used to proxy costs, no statistical analysis of quantities was performed, and no price year was given. These factors limit the generalisability of the results. XAE: The analysis of the clinical study (intention-to-treat or completers) was not stated. Primary health outcomes used were length of follow-up, monthly hospital visits, length of stay, monthly physician visits, monthly day hospital visits, day hospital length of stay and total daily dose. No confidence intervals were reported. XCL: Patients treated with risperidone had significantly fewer hospitalisations and inpatient days than their haloperidol controls. However, patients in the risperidone cohort used more outpatient services. XDI: Mental disorders. XFU: Supported by an unrestricted grant from Janssen Research Foundation, Titusville, NJ, USA. XLI: Costing was undertaken retrospectively on the effectiveness study sample. XRE: Primary outcome results were as follows:length of follow-up, risperidone 17.2 months versus haloperidol 16.0 months, (p=0.6085);monthly hospital visits, risperidone 0.023 versus haloperidol 0.084, (p=0.0040);length of stay, risperidone 19.8 days versus haloperidol 16.64 days, (p=0.5827);monthly physician visits, risperidone 0.441 versus haloperidol 0.244, (p=0.0005);monthly day hospital visits, risperidone 0.03 versus haloperidol 0.003;day hospital length of stay, risperidone 14.31 days versus haloperidol 42 days);and total daily dose, risperidone 4.88 mg versus haloperidol 9.61mg. XSM: No power calculations were reported. Patients were over the age of 18 years and suffering from either schizophrenia, schizoaffective disorder, or major depression with psychotic features and were monitored for at least 6 consecutive months prior to the start of the study (with obtainable medical records). Subjects must have initially scored 50 or below on the Global Assessment of Functioning (GAF) scale. Further, at some time during the final 3 months of the study time frame, patients must have registered a GAF score. No exclusions were reported. There were 28 subjects in the risperidone group (average age 50.0 years, 67.9% female) and 24 in the haloperidol group (average age 54.3 years, 58.3% female). Mean initial GAF scores were 41.4 (risperidone) and 38.3 (haloperidol). XCO: Not included. XCU: US dollars ($). XSA: Confidence intervals and P values were completed for estimated resource costs. XSY: Not stated. XEB: Economic benefits were measured in terms of resource utilisation comparisons and resulting cost comparisons. These were based on the effectiveness results reported above. XCR: The adjusted mean monthly cost totals were $1,636.11 for risperidone and $1,759.45 for haloperidol. XCB: Not performed. XAU: The significant reductions in hospital costs in the risperidone cohort offset higher medication and physician costs. However, total monthly costs for each group were similar. CO1: United States XIM: Although the study conclusions reflect the growing findings around risperidone and haloperidol treatment, methodological issues within the study have produced limitations on the findings therein. KWO: Antipsychotic Agents /economics /therapeutic use; Cohort Studies; Group Practice /economics; Humans; Mental Disorders /drug therapy; Outcome Assessment (Health Care) /economics; Pilot Projects; Risperidone /economics /therapeutic use; United States; Utilization Review XAC: 21998000562 XID: 31 Oct 2000 XLA: English XPR: 10178498 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=21998000562 Record #2 %%%% TTL: Multiple outcome assessment in a study of the cost-effectiveness of clozapine in the treatment of refractory schizophrenia AUT: Rosenheck R, Cramer J, Xu W, Grabowski J, Douyon R, Thomas J, Henderson W, Charney D XSO: Health Services Research XYR: 1998 VOL: 33(5) PAG: 1237-1267 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: Clozapine use in the treatment of refractory schizophrenia. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: Patients with refractory schizophrenia with at least 30-364 days of hospitalisation during the previous year. XSG: The practice settings were Department of Veterans Affairs (VA) medical centres in the USA. XDD: Effectiveness and resource data were collected over a 12 month period between 1996 and 1998 (approximately). No price year was stated. XDR: Discounting was not undertaken due to the short period of analysis (less than 1 year). Direct costs from a societal perspective included inpatient stays, medical/surgical costs, residential care costs, outpatient and treatment costs. No price year was stated. XMB: QALYs were adapted from the primary health outcome findings, according to worst health-good health units (analogous to QALYs). XSD: This was a double-blind, multi-centre randomised controlled trial. The duration of follow-up was 12 months. No loss to follow-up was recorded, although 82% of all assessments through all time points were completed. XSS: Clozapine effectiveness estimates in the treatment of refractory schizophrenia were derived from a single study. OI: The authors made some reference to comparing their findings to those in other papers, although the issue of generalisability to other settings was not addressed. The authors do not appear to have reported their results selectively. The authors reported that the cost intervals found were uncertain and also that using summed weighted z-scores may have resulted in some double-counting. SCO: The rationale for the choice of comparator was clear. VB: The measure of benefit was a utility score appropriate for the patient sample. Conventional QALYs (which focus on physical pain and motor functioning) were not appropriate for patients with psychotic illnesses. It was not clear whether the study sample was representative of the study population due to lack of information provided around patient characteristics, although the authors state that, at baseline, the two groups were comparable. Appropriate statistical analyses were undertaken on the study findings. VC: All relevant categories of cost appeared to have been included in the analysis. Costs were not reported separately from quantities. Resource figures were taken from the VA Cost Distribution Report and computerised workload data. Non-VA health care costs were obtained from another study (Office of the Inspector General, 1992). No sensitivity analysis around costs was conducted and the price year was not given. XAE: The analysis was based on an intention-to-treat basis as well as a crossover exclusion basis. The primary health outcomes used was a Composite Health Index for Schizophrenia (CHIS), developed from combining the weighted results of:(1) the Structured Clinical Interview for Positive and Negative Syndrome Scale (PANSS) for schizophrenia;(2) social relationships;(3) role functioning;(4) general daily activity and recreation;(5) family relationships (using a section of the Quality of Life Interview; and(6) medication side effects (using standard scales).The CHIS evaluated a person's total time in good health through weighted (patient/provider) and non-weighted outcomes. The unweighted clozapine-haloperidol cumulative gain in CHIS was 49% (0-6 months) and 37% (0-12 months). XCL: Clozapine offers clinical benefits in the measure of symptoms and side-effects, and is also more effective than haloperidol on the one-year CHIS. XDI: Mental Disorders. XFU: Supported by the Department of Veterans Affairs Health Services Research Service. XLI: Cost estimates were derived from the study sample. It was not clear whether this information was obtained retrospectively or prospectively. XOP: (1) Rosenheck R A, Cramer J, Xu W, Thomas J, Henderson W, Frisman L K, Fye C, Charney D for the Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. A comparison of Clozapine and Haloperidol in the treatment of hospitalized patients with refractory schizophrenia. The New England Journal of Medicine 1997;337(12):809-13.(2) Office of the Inspector General. Comparison of costs and outcomes of matched pairs of VAMCs and their university affiliates. Washington, DC: Office of the Inspector General,1992. XRE: The effectiveness results were as follows:The patient-weighted clozapine-haloperidol cumulative gain in CHIS was 50% (0-6 months) and 44% (0-12 months).The provider-weighted clozapine-haloperidol cumulative gain in CHIS was 49% (0-6 months) and 41% (0-12 months).Clozapine was significantly more effective than haloperidol in the measure of symptoms (p=0.02) and side-effects (p<0.0001), with nonsignificant trends in the positive direction on community role functioning (p=0.06), family relationships (p=0.23), social relationships (p=0.30), and daily activities (p=0.20).Clozapine was also more effective than haloperidol on the one-year CHIS (p<0.0001). XSM: 423 patient were enrolled in the study (clozapine 205, haloperidol 218). No other patient characteristics were reported within this paper. No power calculations were reported. Details around entry criteria and pharmacological and psychosocial treatment have been presented elsewhere (Rosenheck, Cramer, Xu, et al. 1997). The 2 study groups were shown to be comparable at baseline. XCO: Indirect costs from a societal perspective included lost productivity, benefits, criminal justice and family burden costs. No price year was stated. XCU: US dollars ($). XSA: Costs were statistically analysed (t-test). XSY: Not reported. XEB: Intention-to-treat QALY gains (clozapine-haloperidol) at 0-6 months were 0.008, and over 0-12 months were 0.021. Crossover exclusion QALY gains (clozapine-haloperidol) at 0-6 months were 0.008, and over 0-12 months were 0.027. XCR: the total societal costs were $58,151 for clozapine and $60,884 for haloperidol (t=0.83; p=0.409, non-significant). XCB: The cost-effectiveness ratio results ranged from -$431,585 to $177,352 for clozapine over haloperidol. The change of direction is related to the uncertainty around the cost results and the small changes in benefit. XAU: Clozapine is more cost-effective than standard treatment for use with patients suffering from refractory schizophrenia. Although the magnitude of its effect is small, there is considerable uncertainty around the cost results. CO1: United States XIM: The study suggests that using clozapine is more cost-effective than haloperidol in the treatment of schizophrenia. However, further analysis is required in order to substantiate the cost findings therein as there is a very large confidence interval (which changes direction) which may or may not substantiate such claims. KWO: Clozapine /adverse effects /economics /therapeutic use; Cost-Benefit Analysis; Double-Blind Method; Drug Costs; Haloperidol /adverse effects /economics /therapeutic use; Hospital Costs; Hospitals, Veterans; Humans; Long-Term Care /economics; Outcome Assessment (Health Care) /statistics & numerical data; Patient Admission /economics; Prospective Studies; Psychiatric Status Rating Scales; Quality-Adjusted Life Years; Schizophrenia /diagnosis /drug therapy /economics XAC: 21999008057 XID: 31 Oct 2000 XLA: English XPR: 9865219 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=21999008057 Record #3 %%%% TTL: Clozapine in community practice: a 3-year follow-up study in the Australian Capital Territory AUT: Drew L R, Hodgson D M, Griffiths K M XSO: Australian and New Zealand Journal of Psychiatry XYR: 1999 VOL: 33(5) PAG: 667-675 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: Use of clozapine in community-based patients with recorded diagnosis of schizophrenia or schizoaffective disorder. Compared with typical antipsychotics, clozapine involves additional mandatory blood monitoring and is complicated to prescribe due to the requirements of the Clozaril Patient Monitoring System (CPMS). XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: Patients who had a recorded and appropriately documented diagnosis of schizophrenia or schizoaffective disorder, and whose psychiatric history was known, particularly for the 2 years before commencing clozapine. XSG: Community and primary care. The economic analysis was carried out in Australia. XDD: Effectiveness and resource use data corresponded to patients who commenced clozapine in the Australian Capital Territory (ACT) before 1 July 1994. Clozapine has been used in the ACT since early in 1993, its use having been facilitated by a Commonwealth government-funded Clozapine Co-ordinator. The price year was 1996-1997. XDR: Costs were not discounted despite a time frame of more than 1 year for the cost analysis. Some quantities were reported separately from the costs. Some cost items were reported separately. The cost analysis covered the costs of treatment attributable to bed use (hospital or hostel), clozapine tablets, blood monitoring, and the employment of a Clozapine Co-ordinator (this latter item was estimated to be 0.75 in year 1, 0.50 in year 2 and 0.33 in year 3 postclozapine, representing the proportion of time given to the study cohort). Within the study cohort the number of pathology tests was used as the basis for attributing individual costs of the Clozapine Co-ordinator. The perspective adopted in the cost analysis was not explicitly specified. The source of the cost data was the ACT Health Department. The cost for a bed-day in a psychiatry ward consisted of cost items such as nursing, pathology, imaging, medical, allied health, pharmacy, supplies, on costs and other costs, and overhead costs. The price year was 1996-97. The cost analysis did not cover the costs associated with community services utilised by the patients, either before or after the use of clozapine. XMB: No summary benefit measure was identified in the economic analysis, and only separate clinical outcomes were used, as reported in the effectiveness results. XSD: This was a before and after cohort study, carried out in community practice within the ACT (regional population about 400,000). Data were obtained from records maintained by the ACT hospital and community health system and health services in nearby areas of New South Wales, from other hospital sources when appropriate, and from health workers and the Clozaril Patient Monitoring System (CPMS). The duration of the follow-up was 3 years after the initiation of the use of clozapine, compared with 2 years before. The loss to follow-up was 3 patients. The study cohort was divided into two groups (continuers and discontinuers) on the a priori basis of whether or not they remained on clozapine until the end of the study period without having a total period off clozapine in excess of 3 months in any 1-year. Of the cohort of 37 patients, 25 (68%) were continuers with a mean (SD) age at first prescription of clozapine of 34.5 (8.46) years and 12 (32%), with a corresponding mean (SD) age of 32.9 (8.51), were discontinuers. The only significant difference between the preclozapine demographic and clinical characteristics of the continuers and discontinuers was that the latter had a history of fewer hospitalisations. The reasons for temporarily or permanently discontinuing clozapine were lack of therapeutic response and/or non-compliance (n=6) or intolerable side effects (n=6, 16.2% of the total sample). It was reported that prior to 1 July 1994 in Australia, all patients were required to be under 24-hour supervision (in a hospital or a hostel) when commencing clozapine. XSS: The evidence for the final outcomes was based on a single study. OI: Given the inherent limitations of the study design and the lack of sensitivity analysis addressing uncertainties surrounding the costs and clinical outcomes, some degree of caution should be exercised in interpreting the study results. The issue of generalisability to other settings or countries was not addressed, although appropriate comparisons were made with other studies. As the authors implicitly acknowledge, a cost-utility approach may have been a more appropriate framework in the context in question. This could have incorporated the subjective assessment of the patients regarding the trade-off between the improved clinical outcomes and inconveniences caused due to side effects of the study drug. The issue of whether the study sample was representative of the study population was addressed by pointing out that the study community sample was similar to other samples in studies of clozapine. They were similar in terms of age, sex distribution and age of onset of illness, with the exception that the study sample had less time in hospital preclozapine, and had a shorter index period of hospitalisation and (in most cases) a lower preclozapine BRPS score. SCO: The strategy of not using clozapine was regarded as the comparator. It allowed the active value of the intervention to be evaluated. VB: The authors did not derive a summary measure of health benefit. The analysis was therefore one of cost-consequences design. VC: The validity of the cost results was enhanced by the following features of the cost analysis: some quantities were reported separately from the costs; adequate details of cost estimation were given; the price year was specified; and statistical analysis was performed on resource use and cost data. However, the following features may have adversely affected the validity: it is not entirely clear whether the cost data were based on true costs or charges; the perspective adopted in the cost analysis was not explicitly specified; no discounting was applied; the costs associated with resources used in community practice were not included in the analysis (which the authors perceived as a serious limitation of the study); the effects of the study drug on indirect costs (productivity loss) were not fully addressed by converting the employment status to monetary terms; the cost results may not be generalisable outside the study setting. VM: The internal validity of the effectiveness results may be compromised due to the retrospective nature of the study design, the use of mirror-image comparisons, the lack of blinding procedures and the absence of a control group, as acknowledged by the authors. Furthermore, the claim that the effectiveness analysis being based on intention to treat principle does not appear to be justified given that a complete set of data on clinical outcomes was not presented. No power analysis was conducted to justify the sample size adopted in the study. It was noted that caution would be appropriate concerning the clinical judgements of psychiatrists, which in the context of an open trial may have been influenced by the views of the first author, who was known to be an enthusiast for clozapine (however the fact that two-thirds of all of the cohort were still on clozapine after 3 years was taken as evidence of perceived ongoing clinical benefit of the study drug independently of the study). It was further pointed out that the course of schizophrenia is variable, even in the late stages, and improvements/reduced hospital use could have occurred without any specific interventions. The study sample appears to have been representative of the study population (community-based patients who had refractory psychosis but who had not experienced extensive hospitalisation XAE: The principle used in the analysis of effectiveness was stated to be intention to treat. The clinical outcome measure was change in clinical status (as rated retrospectively for each patient by their treating psychiatrist) using a seven-point scale at the study's end (3 years after commencing clozapine) compared with the period immediately prior to commencing clozapine. Baseline (preclozapine) and progress Brief Psychiatric Rating Scale (BRPS) scores (1-7 rating) were accessed for those patients to whom this scale had been administered. A side-effect checklist developed by the authors was used by the treating psychiatrist to assess retrospectively the side effects after 3 years on clozapine; the experience of epileptic seizures in the periods before or after the commencement of clozapine was also part of the information supplied by the psychiatrist. The living circumstances and employment status in the 6 months prior to the study's end were documented from recorded information and/or from information supplied by relevant mental health workers. It was reported that data for years 1 and 2 preclozapine that did not differ significantly from each other were averaged. XCL: The reported improvement in clinical state following long-term clozapine treatment broadly confirms the previous findings. The absence of improvement in living circumstances in patients on clozapine is not surprising given the low level of institutionalisation at baseline. In contrast to the continuers, the discontinuers did not show a pattern of improvement in outcomes in the 3-year follow-up period. XDI: Behavioral and mental disorders. XRE: The effectiveness results were as follows:At 3 years postclozapine, there was a significant improvement in clinical status for both the cohort (p<0.0001) and the continuers (p<0.0001); 86.1% of the cohort showed moderate or marked improvement and all of the continuers (n=24) showed improvement (half moderate and half marked).Five of nine patients who were not taking clozapine at the study's end were unimproved or had deteriorated.It was reported that there were too few progress (postclozapine) BRPS scores to permit an analysis of the effect of clozapine on BRPS.Side effects present after 3 years on clozapine were weight gain (severe, 1; moderate, 3; mild, 7), increased sleep (moderate, 5; mild, 6), drowsiness (moderate, 2; mild, 7), increased salivation at night (moderate,1; mild, 6) and in the daytime (mild, 5), sweating (moderate, 1; mild, 5), constipation (mild, 5), dizziness (mild, 3), night-time incontinence (mild, 1), and nausea (mild, 1).There were no deaths from suicide in the cohort over the postclozapine period of 3 years; 4 patients had at least one epileptic seizure (two had a prior history of convulsions).There was no change in the number of patients who were institutionalised (in hospital or in a hostel) while on clozapine but there was a significant increase in the number of subjects who were employed or studying at study's end compared with baseline (cohort 21:12, p=0.012; continuers 18:10, p=0.008).Employment and accommodation status in the discontinuers did not change significantly over the study period.The continuers were more likely to be employed or studying 3 years postclozapine (p=0.02). XSM: Power calculations were not used to determine the sample size. A total of 42 patients met the requirements for entry to the study; five were excluded from consideration; one because of death, one because of being admitted to a nursing home during the study period for pre-existing senile dementia, and three being lost to follow-up after moving interstate with their families. The remaining cohort of 37 patients, with a mean (SD) age of 34.0 (8.39) years at first prescription of clozapine, constituted the study sample. XFU: Funded by the Private Practice Trust Fund, the Canberra Hospital. XLI: Costing was performed retrospectively on the same patient sample as that used in the effectiveness analysis. XCO: Despite the fact that employment status was evaluated in the study, no attempt was made to place any value on it. XCU: Australian dollars (Aus$). XSA: The effect of clozapine on time spent in hospitals and hostels, and treatment costs, was examined using Friedman analyses followed by Wilcoxon tests where the former were statistically significant. XSY: No sensitivity analysis was carried out. XEB: See effectiveness results above. XCR: The total costs for the preclozapine period were not significantly different from the costs in any year postclozapine for either the cohort or the continuers.The costs in years 2 and 3 postclozapine were significantly lower than in year 1 postclozapine for both the cohort (year 2, p=0.003; year 3, p=0.02) and the continuers (year 2, p=0.002; year 3, p=0.001).Bed costs (hospital) for the discontinuing group did not change significantly over time.There was no significant difference between the continuers and discontinuers in the total costs of hostel and hospital admissions.Overall, there was no substantive evidence that clozapine use was associated either with an increase or with a decrease in the treatment costs. XCB: Costs and benefits were not combined since the use of clozapine appears to have been the weakly dominant strategy (with better clinical outcomes and equivalent costs). XAU: The findings of significant clinical improvement without evidence of increased cost lend support for the selective use of clozapine in community practice. CO1: Australia XIM: The authors suggest that there is a pressing need for long-term prospective studies (which include measures of change in quality of life) of the use of clozapine, notwithstanding the considerable problems to be encountered in conducting such a study and in the long-term follow-up of patients. KWO: Adult; Antipsychotic Agents /adverse effects /economics; Australia; Clozapine /adverse effects /economics; Community Mental Health Services /economics /standards; Female; Follow-Up Studies; Hospitalization; Hospitals, Psychiatric; Humans; Male; Retrospective Studies; Schizophrenia /drug therapy /rehabilitation; Time Factors; Treatment Outcome XAC: 21999002110 XID: 30 Apr 2001 XLA: English XPR: 10544990 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=21999002110 Record #4 %%%% TTL: Cost-effectiveness of intensive v. standard case management for severe psychotic illness AUT: UK700 Group XSO: British Journal of Psychiatry XYR: 2000 VOL: 176 PAG: 537-543 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of intensive case management for patients with severe mental illness. This consisted of a system of care delivered by trained mental health professionals, which can be distinguished from standard case management by the nature of its reduced caseload, i.e. 10 to 15 rather than 30 to 35. The case managers were given a specific two-day induction course. XTI: Other: case management. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients aged between 18 and 65 years, who had suffered from a psychotic illness for at least two years and who had been admitted to a psychiatric hospital at least twice, once within the past two years. Patients were excluded if they had organic brain damage or a primary diagnosis of substance misuse. XSG: The setting was the community. The economic study was carried out in four inner city areas in UK, of which three were in London and one was in Manchester. XDD: The effectiveness evidence and resource use data were gathered from February 1994 to April 1996. The costs were evaluated in 1997 to 1998 values. XDR: Discounting was carried out since the costs were incurred over two years. The unit costs and the quantities of resources were reported separately. The cost/resource boundary reflected the perspective adopted in the study. The health costs included in the analysis were for the case managers or community mental health team (CMHT), hospital services, primary care, medication, accommodation, prison and police custody, social and non-statutory services. The resources were estimated using actual data derived from the trial. The unit costs were estimated from several sources, such as official salaries for personnel, local providers for hospital and social services, Personal Social Services Research Units for primary care, and a local prison for police custody. The quantities of resources were measured from February 1994 to April 1996. The costs were evaluated in 1997 to 1998 values. XMB: No summary benefit measure was used in the economic analysis, due to the lack of a statistically significant difference between the study groups in term of the effectiveness. A cost-minimisation analysis was therefore carried out, although the authors analysed the relationship between the costs and the primary health outcome. XSD: This was a randomised controlled clinical trial carried out in four centres (St. George's Hospital, St. Mary's Hospital and King's College Hospital in London, and Manchester Royal Infirmary in Manchester). Randomisation was stratified by centre and was conducted by an independent statistical centre. Researchers, independent of those providing clinical care, conducted assessments at baseline, 12 and 24 months. The average length of follow-up was 104 weeks in both groups and 14 patients were lost to follow-up. XSS: The effectiveness data were derived from a single study. OI: The authors made some comparisons of their findings with those from other studies. They also addressed the issue of the generalisability of the study results to other locations in UK in the sensitivity analyses. Thus, the external validity of the study, already enhanced by the separate analysis of the unit costs and quantities, should be high. Patients with severe psychotic illness were enrolled in the study and this was reflected in the conclusions. The authors reported the study results in appropriate detail. SCO: The rationale for the choice of the comparator was clear. Standard case management represented the usual intervention for the management of patients with sever psychotic illness. You should assess whether it represents a widely used intervention in your own setting. VB: No summary benefit measure was used in the economic analysis, since there was no difference in the outcome measures assessed in the effectiveness analysis. However, the authors assessed the relationship between the primary outcome and the total costs of the interventions. VC: The authors stated that a societal perspective was adopted, and direct medical and non-medical costs were included in the analysis. The impact of the indirect costs, which were not estimated, was assessed. It would appear that the study results were quite robust, due to the fact that productivity losses were probably similar in the study groups. The unit costs and the quantities of resources were reported separately and several statistical analyses were carried out. The price year was adequately reported and several sensitivity analyses were performed on the cost side. The validity of the cost results is, therefore, likely to be high. VM: The analysis of the effectiveness used a multicentre, randomised controlled trial, thus enhancing the internal validity. The sample size was large enough to detect statistically significant differences in the economic analysis and, therefore, was large enough to meet the requirements of the effectiveness analyses. The study sample appears to have been representative of the study population. The period during which the effectiveness evidence was collected was reported. The basis for the analysis of the clinical study was intention to treat. However, no baseline comparison of the study groups was reported, although there was no difference between those patients participating and not participating. The potential role of bias and confounding factors should be limited given the randomised design of the study. XAE: The basis for the clinical analysis was intention to treat. The primary health outcome was the number of days in hospital for psychiatric problems over 24 months, recorded in a modified World Health Organization (WHO) Life Chart. The secondary outcome measures included:clinical status, assessed using the Comprehensive Psychiatric Rating Scale (CPRS);quality of life, assessed using the Lancashire Quality of Life Profile;unmet needs, recorded using the Camberwell Assessment of need;social disability, measured by the WHO Disability Assessment Schedule (DAS); andpatient satisfaction assessed, using a self-reported questionnaire.No comparability of the study groups was reported in the present study (details were reported elsewhere - see "Other Publications of Related Interest" below), although the authors stated that there was no difference between those patients who were included in the analysis and those who were excluded. XCL: The authors concluded that the two case management approaches were similar as there was no statistically significant difference in any outcome measure. XDI: Mental disorders; Health care: Patient care management. XFU: Funded by the UK Department of Health and NHS Research and Development programme. XLI: The costing was undertaken prospectively on the same patient sample as that used in the effectiveness analysis. XOP: UK700 Group (Burns T, Creed F, Fahy T, et al) (1999). Intensive versus standard case management for severe psychotic illness trial. UK700 Group. Lancet 1999; 353: 2185-2189. XRE: There was no statistically significant difference between the intensive and standard groups in terms of the following outcome measures:the hospital days over 24 months were 73.5 in the intensive group and 73.1 in the standard group (difference 0.4 days, 95% confidence interval, CI: -17.4 - 18.1);the CPRS scores were 18.5 in the intensive group and 18.1 in the standard group (difference 0.4, 95% CI: -1.8 - 2.7);the quality of life scores were 4.58 in the intensive group and 4.55 in the standard group (difference 0.04, 95% CI: -0.09 - 0.16);the number of unmet needs was 1.84 in the intensive group and 2.13 in the standard group (difference -0.29, 95% CI: -0.68 - 0.11);the mean DAS total scores were 1.10 in the intensive group and 1.13 in the standard group (difference -0.03, 95% CI: -0.16 - 0.10); andthe mean patient's satisfaction scores were 16.7 in the intensive group and 17.1 in the standard group (difference -0.3, 95% CI: -1.2 - 0.5). XSM: Power calculations were not reported in the current study (reported in the clinical study - see "Other Publications of Related Interest" below) for the effectiveness analysis, but were performed for the costing. The patients were identified by a review of the inpatient and outpatient registers at the study hospitals. In total, 708 patients were identified, but 41 were excluded from the analysis due to death (n=15), loss to follow-up (n=14) or insufficient information for the costing (n=12). Overall, 667 patients were included in the study. Of these, 335 were in the intensive group and 332 in the standard group. XCO: The indirect costs related to the expenses for the patient and family and productivity losses were not included in the main analysis. However, the authors discussed their impact. XCU: UK pounds sterling (). XSA: Power calculations were derived from a previous study. These indicated that a sample size of 350 patients in each group could detect a difference of 45 in the average weekly cost per patient as statistically significant at the 5% level, with 80% power. Statistical analyses of the total costs were also carried out to test for statistical significance of the results. Sub-group analyses were carried out using tests of interaction. Finally, multiple regression was used to adjust for the baseline characteristics of the patients, such as centre, age, gender, ethnic group, CPRS, social class, and duration of illness. XSY: One-way sensitivity analyses were carried out to assess the robustness of the estimated costs to variations in the unit costs, discount rate, capital overheads as a percentage of CMHT staff costs, and the inflation rate of case manager costs for non-event recorded to event recorded time. Key cost drivers, psychiatric inpatient care and staffed accommodation were varied to assess the generalisability of the study results to other locations in UK. XEB: See the 'Effectiveness Results' section. XCR: No statistically significant difference was found in the total costs of case management in the two groups, either in the main analysis or in the sub-group analyses.The total two-year costs amounted to 24,553 (+/- 23,408) in the intensive group and 22,704 (+/- 22,000) in the standard group, with a cost difference of 1,849 (95% CI: -1,605 - 5,304).The median two-year cost (90% range) was 15,912 (2,232 to 73,035) in the intensive group and 14,736 (1,001 to 62,180) in the standard group.The estimated costs were not sensitive to variations carried out in the sensitivity analyses. XCB: A formal synthesis of the costs and benefits was not carried out, due to the lack of statistical significance in terms of both the effectiveness and the costs. The authors explored the relationship between the costs and length of hospitalisation. They found that psychiatric inpatient costs comprised almost half of the total costs of care for patients in both groups (47% for intensive care and 48% for standard care). Overall, there was no evidence that intensive care was more cost-effective than standard care, or vice versa. XAU: Intensive case management was not more cost-effective than standard case management for patients with severe psychotic illness. In terms of the estimation of the indirect costs, the authors commented that "given the lack of differences between the two groups in outcomes and resource utilisation, it seems reasonable to assume that patients and family costs would also differ little". They also added that the exploration of months in full-time employment and months' unemployed revealed no significant differences between the study groups. Consequently, the inclusion of the indirect costs would not change the basic results of the analysis. CO1: United Kingdom XIM: The main implication of the analysis is that "the policy of advocating intensive case management for all patients with severe psychosis is not supported by these results and needs to be re-examined". KWO: Adolescent; Adult; Aged; Cost-Benefit Analysis; Critical Care /economics; Follow-Up Studies; Hospitalization /economics; Humans; Middle Aged; Psychotic Disorders /economics /ethnology /therapy; Treatment Outcome; West Indies /epidemiology XAC: 22000008185 XID: 31 Jan 2003 XLA: English XPR: 10974959 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22000008185 Record #5 %%%% TTL: Cost-effectiveness analysis of case management versus a routine community care organization for patients with chronic schizophrenia AUT: Chan S, Mackenzie A, Jacobs P XSO: Archives of Psychiatric Nursing XYR: 2000 VOL: 14(2) PAG: 98-104 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study examined case management for the care of mentally ill patients in comparison with traditional care. Case management is a team approach to care with providers being organised into formal teams. The prime liaison between the patient and the team is the case manager, who co-ordinates the care, helping to channel the patient to appropriate modes of care. XTI: Treatment XEC: Cost-effectiveness analysis. XPA: The study population consisted of patients with chronic schizophrenia. The inclusion criteria were suffering from schizophrenia for at least 2 years, at least 3 hospitalisations in the past 24 months before admission, requiring supervision in living skills, being unemployed for at least 3 months, and being unreliable in terms of compliance with treatment. Patients aged under 18 or over 65 years were excluded. XSG: The practice setting was the community. The economic analysis was conducted in Hong Kong. XDD: The effectiveness data were collected between 1997 and 1998. Resource used was derived from the community psychiatric team annual report, which was published in 1998. The price years were not reported. XDR: The direct costs included only the medical costs. These were the costs of visits from CPNs or case managers, telephone consultations, services from medical social workers and clinical psychologists, outpatient visits, day hospital, sheltered workshops and hospitalisation. The total and mean costs were calculated. The average costs per visit were based on the actual time per visit. The cost estimates were based on service utilisation measurement, as derived from the community psychiatric team annual report (1998). The unit costs were reported. The costs and the quantities were not reported separately. Discounting was unnecessary. The price year was not stated. XMB: The authors did not develop a summary benefit measure. Hence, a cost-consequences analysis was performed. XSD: The study was a randomised prospective study that was conducted in a single centre. Both groups were followed up for 6 months. No loss to follow-up was reported. Ten community psychiatric nurses (CPNs) were chosen as case managers. The case managers were given explicit protocols of care and the patients were monitored closely. XSS: The effectiveness data were gathered from a single study. OI: The authors made appropriate comparisons of their findings with those from other studies. However, because the authors did not report a synthesis measure of the cost and effectiveness of the intervention (e.g. cost per life-year saved or cost per quality-adjusted life-years gained), it was not possible to compare the results with those from other well-accepted programmes. In addition, given the small sample size, the results of the study may not be generalisable to the study population and to other settings. The authors did not present their results selectively and reported further limitations of their study. In particular, the absence of economic data for caregivers, the relatively small sample size, and the experimental conditions which exclude prediction in a non-experimental situation. SCO: The reason for the choice of the comparator was clear. It represented the standard community care for patients with chronic schizophrenia in the authors' setting. You should consider whether this is a widely used technology in your own setting. VB: There was no summary measure of benefit in the economic analysis. VC: All the categories of cost relevant to the perspective adopted (health care provider) appear to have been included in the analysis. The costs and the quantities were not reported separately and the costs for a single price year were not explicitly stated. Neither statistical nor sensitivity analyses were carried out, which may limit the internal validity of the findings. These factors tend to limit the generalisability of the cost results to other settings. The authors performed appropriate currency conversions. Discounting was unnecessary since all the costs were incurred in 6 months,. VM: The analysis used a randomised prospective study, which was appropriate for the study question. Since the study sample was approximately 5% of the study population, it is uncertain whether it was representative of the study population. The patients were shown to be comparable at analysis in terms of age and gender, so confounding should be low for these variables. The influence of selection bias is also likely to have been low due to randomisation. The authors acknowledged that measurement bias may have been possible (better outcomes in the experimental group) because the case managers were given explicit protocols of care and the patients were monitored closely. XAE: The analysis of the clinical study was conducted on an intention to treat basis. The primary health outcomes used in the analysis were the patient's mental condition, the behavioural functioning and daily skills of the patient, the patient's satisfaction and the readmission rate. The Brief Psychiatric Rating Scale (BPRS) was used to assess the client's mental condition. Both experimental and control groups were assessed twice, at the time of selection and 5 months after inclusion. The Specific Level of Functioning Scale (SLOF) was used to assess the behavioural functioning and daily skills of the clients. Both experimental and control groups were also assessed twice. The Patient Satisfaction Instrument (PSI) was used to assess patient and client satisfaction with nursing care in the community setting. The satisfaction with the service was assessed after a 5-month intervention period. The readmission rate was assessed after completion of the 5-month intervention. XCL: Case management was associated with improvements in psychological and functional outcomes and patient satisfaction. XDI: Health care: Patient care management; Mental disorders. XFU: Supported by the Health Services Research Committee. XLI: The costing was undertaken on the same group as that used in the effectiveness study. XOP: Gorey KM, Lesile DR, Morris T, et al. Effectiveness of case management with severely and persistently mentally ill people. Community Mental Health Journal 1998;34:241-50.Sands RG, Cnaan RA. Two modes of case management: assessing their impact. Community Mental Health Journal 1994;30:441-57.Tyrer P, Morgan J, Van Horn E, et al. A randomised controlled study of close monitoring of vulnerable psychiatric patients. Lancet 1995;345:756-9.Johnston S, et al. Intensive case management: a cost-effectiveness analysis. Australian and New Zealand Journal of Psychiatry 1998;32:551-9. XRE: The patients in the experimental group had significantly better outcomes in the overall BPRS score, (p<0.001). Also, in the items relating to conceptual disorganisation, (p=0.008), tension, (p<0.001), suspiciousness, (p=0.035), hallucinatory behaviour, (p<0.001), and unusual content, (p=0.011).The patients in the experimental group had significantly better outcomes in the overall SLOF score, (p<0.001). Also, in the items relating to personal care skills, (p<0.03), interpersonal relationship, (p<0.05), social acceptability, (p<0.03), and community living skills, (p<0.001).The patients in the experimental group had significantly better outcomes in the PSI.The experimental group believed that the case managers had more time to talk to them, (p=0.006), and gave them a feeling of security, (p=0.04).There was no difference between the two groups in the readmission rate. XSM: No power calculations to determine the sample size were reported. Of the 146 patients assessed in the study, 96 met the criteria for inclusion. Thirty-four patients refused to participate. Thus, the final number of patients was 62. These were randomised to either case management (n=31; experimental group) or conventional care (n=31; control group). There was no significant difference between the groups in the baseline assessment. The age and gender were identical in the two groups. XCO: No indirect were included in the analysis. XCU: Hong Kong dollars (HK$). Conversions were undertaken using a rate of HK$8 = US$1. XSA: No statistical analysis of the costs was carried out. XSY: No sensitivity analysis was carried out. XEB: See the 'Effectiveness Results' section. XCR: The mean cost for each intervention was calculated and compared.The mean cost was HK$14,833 (standard deviation, SD=$1,539) for the experimental group and HK$11,230 (SD=$7,979) for the conventional group, (p=0,017).Case management increased the costs by HK$3,600 (US$450) per person.The major difference between the two groups was due to a large number of case manager visits in the experimental group (mean 9.26, SD=1.72) versus CPN visits in the conventional group (mean 4.94, SD=1.89). XCB: Not applicable. XAU: Case management was more costly than the conventional Community Psychiatric Nursing Service. During a 5-month period, case management was associated with improvements in psychological and functional outcomes and patient satisfaction. CO1: Hong Kong XIM: The results of this study will inform policy makers about resource allocation and policy development in the implementation of case management for the care of mentally ill clients. Further studies using the same model of case management, but with larger sample sizes, are recommended. KWO: Adult; Case Management /economics; Community Mental Health Services /economics; Cost-Benefit Analysis; Female; Hong Kong; Humans; Male; Middle Aged; Outcome Assessment (Health Care); Psychiatric Nursing /economics; Schizophrenia /rehabilitation XAC: 22000007580 XID: 31 Jan 2004 XLA: English XPR: 10783528 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22000007580 Record #6 %%%% TTL: Evaluation of outcomes in converting from intravenous ondansetron to oral granisetron: an observational study AUT: McCune J S, Oertel M D, Pfeifer D, Houston S A, Bingham A, Sawyer W T, Lindley C M XSO: Annals of Pharmacotherapy XYR: 2001 VOL: 35(1) PAG: 14-20 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: Prescribing guidelines for drug therapy based on oral granisetron, a 5-HT3 antagonist, to prevent acute chemotherapy-induced nausea and vomiting (CINV) in cancer patients. XTI: Guidelines. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients suffering from cancer and undergoing chemotherapy. XSG: The setting was community. The economic study was carried out at the University of North Carolina, NC, USA. XDD: Effectiveness and resource data were collected between 1 July 1995 and October 1996. 1995 prices were used. XDR: Discounting was not carried out as costs were incurred over a period of time less than 2 years. Quantity and costs were not reported separately. The estimation of costs was based on actual data collected in 1995. The quantity/cost boundary was not clear, given that only drug acquisition costs were included in the analysis and that these can be born by patients, hospital or third party payer. XMB: Clinical outcomes were not aggregated and no summary benefit was used in the economic analysis, thus a cost-consequence analysis was conducted. XSD: The study was a population-based case-control study and all patients (interviews) included in the study were accounted for in the analysis. The study was carried out at the University of Carolina Hospitals and Clinics. Interviews were conducted by one of five interviewers, all of whom were trained by the senior author of the paper. Patients were followed till the suspension of the drug regimen. XSS: The effectiveness evidence was derived from a single study. OI: The issue of generalisability to other settings was not addressed and the robustness of the results was not tested using sensitivity analyses. However, the authors compared their findings with those from other studies and similar conclusions were drawn, especially on the effectiveness side of the analysis. The analysis presents some limitations, particularly related to the study design, as recognised by the authors. SCO: The selected comparator was clearly, and appropriately, represented by the prescribing guidelines adopted before the introduction of the new protocol. VB: Not applicable. VC: The cost estimates are likely to be specific to the institutions considered in the study. Only drug acquisition price was used in the analysis and this could vary according to the payer status (patient, third party payer, or hospitals). Perhaps societal costs should have been included since patients' functional status may be heavily affected by the success rate of the drug therapy (total control or major control), and this could have an impact on the level of care these patients need (from family or some institutions). VM: Even though the observational study was population-based, the internal validity of the analysis could have been limited not only by the lack of randomisation, but also by some biases due to the uneven allocation of participants to the two groups (i.e. more patients were administered ondansetron in Period 2). XAE: The primary health outcomes used in the study were derived from the interviews: a standardised series of 9 questions were asked in reference to the day of chemotherapy administration. The following outcomes were assessed through the patients' rating on a verbal analogue scale (0 none, 10 as severe as possible): nausea severity, effect of the nausea on daily function, quality of life, and satisfaction with antiemetic control. Total control of nausea and vomiting was defined as no emesis episode and a nausea rating of 0, major control as one or two emesis episodes and/or nausea rating of 1-3. All patients experiencing more than two emesis episodes or nausea rated greater than 3, were classified as control failures. For hospitalised patients, the medication record was evaluated for the administration of rescue antiemetics. Guideline compliance was also assessed by comparing the prescribing regimen with institution guidelines. Several statistical tests were conducted in order to compare the groups in the three periods considered. The two populations (Periods 1 and 2, compared with Period 3) were comparable with respect to demographic characteristics and clinical conditions. XCL: The analysis showed that ondansetron and granisetron were both effective in preventing acute CINV in cancer patients. After the introduction of new prescribing guidelines, the compliance rate for the new drug increased over time. XDI: Neoplasms. XFU: None stated. XLI: Costing was undertaken prospectively from the same patient sample as that used in the effectiveness study. XRE: The effectiveness results were as follows:The frequency of total control in ondansetron patients was 56% and granisetron patients 60% in the first population (Periods 1 and 2), and 50% in ondansetron patients and 54% in granisetron patients in Period 3.Frequency of major control in ondansetron patients was 10% and granisetron patients 13% in the first population (Periods 1 and 2), and 11% in ondansetron patients and 17% in granisetron patients in Period 3.For hospitalised patients, the use of rescue antiemetics in ondansetron patients was 32% and in granisetron patients 30% in the first population (Periods 1 and 2), and 12% in ondansetron patients and 19% in granisetron patients in Period 3.Immediately following guideline modification (Period 2), the rate of guideline compliance was about 61% (percentage of patients who were prescribed oral granisetron, as recommended). In Period 3, the rate of compliance was 78%. XSM: Patients were identified through daily reviews of the pharmacy database. All adult and paediatric (older than 5 years) oncology patients were eligible. Patients receiving a haematopoietic stem-cell transplant were excluded because of an ongoing clinical trial of intravenous granisetron in this population. Patients were also excluded if they were excessively sedated or could not understand English. Eligible patients were interviewed each time they were administered a dose of 5-HT3 antagonist prior to chemotherapy (patients receiving multi-day chemotherapy were interviewed as many times as the number of doses they received). Three periods of time were considered:a four-week period immediately prior to guideline revision (Period 1, July 1995);a five-week period immediately after the revision (Period 2, August 1995);and a five-week period one year after guideline revision (Period 3, October 1996).Data on Periods 1 and 2 were combined and then compared to Period 3. Data were collected for about 85% of eligible patients. A total of 608 patient interviews were conducted: 187 patients provided 433 interviews during Periods 1 and 2, and 70 patients provided 175 interviews in Period 3. Power calculations were retrospectively performed based on the existing sample size: there was less than 80% power to detect a difference in the means of data in Periods 1 and 2; however, power of greater than 80% was present to detect a difference in emesis episode between patients receiving the two drug regimes. XCO: Indirect costs were not included. XCU: US dollars ($). XSA: No statistical analysis of costs was carried out. XSY: No sensitivity analysis was performed. XEB: See effectiveness results above. XCR: The cost results were as follows:The acquisition price was $4.20 for ondansetron (1 mg) and $25.86 for granisetron (1 mg). Total costs of each period were calculated.In Period 1 only ondansetron was used, and the total cost of the 199 treatments carried out was $21,230, resulting in an average cost per treatment of $107.In Period 2, both the drugs were used in the guidelines and the total cost of 233 treatments was $16,683 ($7,031 for patients treated with ondansetron and $9,652 for those treated with granisetron). The average cost per treatment was $72.In Period 3, both drugs were still used and the total cost of the 174 performed treatments was $11,328 ($4,320 for ondansetron and $7,008 for granisetron), yielding an average cost of $65 per treatment. XCB: Not applicable. XAU: Over time, the revision of institutional antiemetic guidelines for prevention of acute CINV was successful both in ensuring the same effectiveness as before and in resulting in cost savings for patients and institutions. CO1: United States XIM: The main implication of the study was that the introduction of the new prescribing protocol was successful, given that guideline revision and outcome documentation by the oncology pharmacists resulted in increased compliance with institution guidelines and a 40% cost saving. KWO: Administration, Oral; Adolescent; Adult; Antiemetics; Child; Constipation /chemically induced; Diarrhea /chemically induced; Drug Utilization Review /statistics & numerical data; Drug-Related Side Effects and Adverse Reactions; Female; Granisetron; Guideline Adherence /statistics & numerical data; Headache /chemically induced; Humans; Injections, Intravenous; Male; Middle Aged; Ondansetron; Organizational Policy; Treatment Outcome XAC: 22001000261 XID: 28 Feb 2002 XLA: English XPR: 11197579 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22001000261 Record #7 %%%% TTL: Cost-utility of risperidone compared with standard conventional antipsychotics in chronic schizophrenia AUT: Oh P I, Lanctot K L, Mittmann N, Iskedjian M, Einarson T R XSO: Journal of Medical Economics XYR: 2001 VOL: 4 PAG: 137-156 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of risperidone (RIS) to ameliorate the negative symptoms of schizophrenia. Risperidone is a benzisoxazole derivative with combined serotonin and dopamine receptor blocking properties. XTI: Treatment. XEC: Cost-utility analysis. XPA: The study population comprised patients suffering from chronic schizophrenia. This was defined as at least two years of more or less continuous thought disturbance, with the disturbance including pronormal, active and residual phases. XSG: The setting was not explicitly stated. The economic study was carried out in Canada. XDD: The effectiveness evidence was gathered from studies published between 1966 and 1995. The price year was 1997. XDR: Discounting was irrelevant as all the costs were incurred over one year. The unit costs were reported separately from the quantities of resources used. The cost items included in the economic analysis were drug acquisition, psychiatric visits, community nursing visits, community social worker visits, community care manager visits, community residential care per day, hospital stay for acute admission and for prolonged admissions beyond 8 weeks, and relapse. The cost/resource boundary adopted was that of the government payer in Canada. The costs were estimated using actual data, which were mainly derived from provincial health insurance plans. The resource use was estimated on the basis of clinical practice in Canada. The price year was 1997. XMB: QALYs were used as the benefit measure in the economic analysis. The utility values derived from a sample of patients were combined with survival data derived from the review of the literature. The overall QALYs for each treatment were obtained using a decision model. XOA: The outcomes assessed in the review and used as model inputs were the probabilities of efficacy, dropout due to lack of efficacy, dropout due to adverse events, and EPSs with all drugs. XSD: The effectiveness analysis was based on a single group of patients who voluntarily provided the estimates of the outcomes. No follow-up was required. XSS: MEDLINE, EMBASE and International Pharmaceutical Abstracts were searched from 1966 to 1995. The search was restricted studies conducted in humans and reported in the English language. The keywords used were "schizophrenia" and "risperidone" (or "haloperidol decanoate" or "fluphenazine decanoate"). All papers and review articles were cross-referenced manually. XSS: The effectiveness evidence was mainly derived from a review of published studies and experts' opinions. The authors also conducted a single study to derive the utility weights used in the analysis. CED: Only randomised controlled trials were included in the review. The inclusion criteria of the review were:original clinical trial;random allocation to treatment groups;one group was administered either oral RIS (4 to 10 mg/day), HAL-DEC or FLU;the trial was controlled by either placebo or active comparator medication;double-blind technique;the patients were women or men aged 18 years or over;the patients were diagnosed with schizophrenia using standardised criteria;acceptable criteria had been used to define chronic schizophrenia;the length of the treatment was at least 4 weeks; andappropriate standardised instruments were used to measure the outcomes.Primary studies were excluded if information on medications, patients, hospitalisation, dropouts and so on, could not be extracted. EST: A decision analytic model was used to estimate the costs and utility values associated with the treatments. The typical patient considered in the model was a 40-year-old inpatient with a 10- to 20-year duration of paranoid schizophrenia. The patient also had an initial Brief Psychiatric Rating Scale score of 55 or a Positive and Negative Symptoms Scale for schizophrenics score of 90 (range: 60 - 120), indicating a moderate degree of psychotic symptoms. The patient started the therapy with the prescribed drugs. The possible events were then the development of tolerability (presence or absence of treatment-limiting side effects), the development of extra-pyramidal symptoms (EPSs), success or failure, discharge from hospital, and relapse. The time horizon of the model was one year. OI: The authors compared their findings with those from other studies, which confirmed the results of the present analysis. The issue of the generalisability of the study results to other settings was addressed. Several sensitivity analyses were carried out and the unit costs were reported separately for the resources used, thus enhancing the external validity of the analysis. The results of the sensitivity analyses were presented in detail. A population of patients with chronic schizophrenia was considered in the study and this was reflected in the conclusions of the authors. The authors noted that their findings should not be generalised to the whole population of patients suffering from schizophrenia, especially those patients in the early stages of the disease. SCO: The authors justified their choice of the comparators. HAL, HAL-DEC and FLU represented widely used antipsychotics in Canada. You should assess whether they represent widely used treatments in your own setting. VB: QALYs were used as the benefit measure in the economic analysis. No discounting of the benefits was required, as the time horizon of the analysis was one year. The overall benefits were obtained using a decision model. The use of QALYs allows the comparison of the treatment with other interventions funded in the health care system. VC: The perspective adopted in the study was stated and all the relevant categories of costs appear to have been included in the analysis. The authors stated that a societal perspective was not adopted, as estimates of the indirect costs were unavailable. A complete breakdown of the costs was provided. Also, the unit costs were reported and the price year was given. This enhanced transparency and generalisability, and simplified any reflation exercise to other settings. The costs were treated deterministically, but sensitivity analyses were carried out, varying any cost parameter used in the model. The dominance of RIS was not sensitive to wide variations of the unit costs. The cost estimates were specific to the Canadian setting, but they were reported in full. VM: The effectiveness measures were mainly estimated from a review of primary studies. The search methods and the inclusion criteria were reported in detail. Only randomised controlled trials providing good-quality data were considered. A meta-analysis was conducted to combine the estimates from the primary studies. Confidence intervals were provided and were used in the sensitivity analyses. Some assumptions made by experts were also required, but this was due to the lack of reliable published data. The ranges were used for the sensitivity analysis. The utility values were derived from a small primary collection of data, obtained from patients who voluntarily participated in the study. The authors noted that measurements carried out on a larger sample of patients would have been preferable. Uncertainty around these estimates was dealt with by carrying out sensitivity analyses. The estimated cost-utility ratios were robust to both the assumptions and utility values. The authors acknowledged that adherence to prescribed regimens was not considered in the model, but the compliance rates were expected to be higher with RIS than with the other treatments, thus supporting the dominance of RIS. XAE: All 32 patients provided data on utilities. During 30-minute one-to-one interviews, the patients assessed the utility of different health states associated with schizophrenia. The method used was the standard gamble technique. The scenarios to be assessed were moderate paranoid delusions in a hospitalised patient, mild delusional symptoms in a hospitalised patient (one for each drug), mild delusional symptoms in a patient living in the community, and drug side effects including EPSs. An internal check was carried out, as the utility values were also collected on a visual analogue scale to confirm that the patients understood the task. XBC: Data obtained from the primary studies were combined through a meta-analysis, using a random-effects model. As a result, 95% confidence intervals (CIs) were reported. XBD: The authors investigated the differences between the primary studies and ensured that the populations of the primary studies were similar. XBM: Two raters assessed the validity of the primary studies to be included in the review. XBP: Seventeen primary studies were used in the review of the effectiveness evidence. XBV: Studies not meeting the inclusion criteria were not considered. XCE: Expert opinion was used to assess some of the outcome measures not found in the published literature. These outcomes were the rates of discharge if symptoms improved and relapse within one year. XCF: The rate of discharge if symptoms improved was 0.81 (range: 0 - 1) and the relapse rate within one year was 0.16 (range: 0 - 1). It was also assumed that a successfully discharged patient would live in a supervised residential care environment, and any relapses were assumed to occur near the end of the evaluation period. XCL: This part of the effectiveness analysis was used to calculate the overall quality-adjusted life-years (QALYs) associated with each drug treatment. XDI: Mental disorders. XFU: Supported by Janssen-Ortho Canada. XLI: The costing was carried out on a different sample of patients from that used in the effectiveness analysis. XRE: The average utility rating was 0.83 (+/- 0.06) for moderate symptoms;the average utility rating was 0.91 (+/- 0.03) for mild symptoms with RIS;the average utility rating was 0.90 (+/- 0.04) for mild symptoms with HAL, HAL-DEC and FLU;the average utility rating was 0.84 (+/- 0.04) for mild symptoms with HAL, HAL-DEC or FLU plus EPSs;the disutility of hospitalised patients was 0.07; andthe disutility for EPS was 0.06.The internal check confirmed the validity of the results. XSM: A sample of 32 volunteers was used to derive the utility weights used in the cost-utility analysis. The sample was predominantly male (90.6%) with a mean age of 35.6 (+/- 8.8) years (range: 24 - 59). The mean duration of schizophrenia in this patient group was 13.3 (+/- 7.1) years (range: 1 - 33). The method used to select the sample was not reported. Power calculations to determine the sample size were not carried out. XRR: The average efficacy rate was 0.67 (95% CI: 0.60 - 0.75) with RIS, 0.50 (95% CI: 0.32 - 0.68) with HAL, 0.46 (95% CI: 0.28 - 0.65) with HAL-DEC, and 0.39 (95% CI: 0.29 - 0.50) with FLU.The dropout rate due to lack of efficacy was 0.14 (95% CI: 0.06 - 0.21) with RIS, 0.28 (95% CI: 0.09 - 0.47) with HAL, 0.02 (95% CI: 0 - 0.06) with HAL-DEC, and 0.02 (95% CI: 0 - 0.05) with FLU.The dropout rate due to adverse events was 0.07 (95% CI: 0.05 - 0.08) with RIS, 0.06 (95% CI: 0.03 - 0.10) with HAL, 0.03 (95% CI: 0 - 0.07) with HAL-DEC, and 0.05 (95% CI: 0 - 0.11) with FLU.The rate of EPS was 0.26 (95% CI: 0.20 - 0.33) with RIS, 0.48 (95% CI: 0.31 - 0.65) with HAL, not assessed with HAL-DEC, and 0.29 (95% CI: 0.07 - 0.51) with FLU. XCO: The indirect costs were not included in the analysis. XCU: Canadian dollars (Can$). XSA: No statistical analysis of the costs was carried out. XSY: One-way sensitivity analyses were carried out on all variables included in the decision model, to assess the robustness of the estimated cost-utility ratios. The 95% CIs were used for the effectiveness data, while all the costs were varied over a range of 50 to 150% of the baseline costs. A threshold analysis was also carried out. This calculated the point at which the conclusions of the analysis shifted from one strategy to the other, or became neutral. XEB: The expected QALYs over one year were 0.87 with RIS, 0.83 with HAL, 0.84 with HAL-DEC, and 0.83 with FLU. XCR: The expected one-year costs were Can$69,855 with RIS, Can$76,353 with HAL, Can$78,388 with HAL-DEC, and Can$82,264 with FLU. XCB: An incremental cost-utility analysis was carried out to combine the costs and benefits of each treatment. However, the incremental cost-utility ratios were not calculated as the RIS-based treatment was dominant (more effective and less costly) over the other interventions. The dominance of RIS was not affected by variations in the cost data, while the QALYs were more sensitive to variations in the efficacy rates and utility values. XAU: Risperidone (RIS) proved to be a cost-effective treatment for patients with chronic schizophrenia. It was associated with less costs and higher effectiveness than other currently used treatments. CO1: Canada XIM: The authors point out that further comparisons between RIS and other atypical antipsychotics should be carried out. In addition, local systems and networks should be activated in order to reduce hospitalisation and increase cost-savings. This was generally a well-designed and clearly reported study. KWO: Adult; Antipsychotic Agents /administration & dosage /economics; Canada; Cost-Benefit Analysis; Fluphenazine /administration & dosage; Haloperidol /administration & dosage; Humans; Patient Compliance; Risperidone /administration & dosage; Schizophrenia /drug therapy; Treatment Outcome XAC: 22002008065 XID: 28 Feb 2003 XLA: English DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22002008065 Record #8 %%%% TTL: Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder: health-related quality of life and medical cost outcomes AUT: Revicki D A, Paramore L C, Sommerville K W, Swann A C, Zajecka J M XSO: Journal of Clinical Psychiatry XYR: 2003 VOL: 64(3) PAG: 288-294 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of divalproex sodium and olanzapine to treat acute mania associated with bipolar disorder. Treatment with divalproex was initiated at 20 mg/kg per day, while treatment with olanzapine commenced at 10 mg/day. The doses of both drugs could be increased if symptoms persisted. The maximum daily dose was 20 mg/kg plus 1,000 mg/day for divalproex and 20 mg/day for olanzapine. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients with bipolar disorder who experience episodes of acute mania. Patients were eligible for inclusion in the trial if they had a DSM-IV diagnosis of bipolar disorder Type I and scored at least 25 on the Mania Rating Scale (MRS). They also had to be aged between 18 and 65 years, and be hospitalised for an acute manic episode. In addition, female patients of childbearing age were required to be using effective contraception. The exclusion criteria included pregnancy or intention to become pregnant, schizoaffective disorder, unstable medical condition, and alcohol or substance dependence. Other exclusion criteria were a history of intolerance or treatment failure after treatment with divalproex or olanzapine, depot psychoactive medications, or mood disorder secondary to the medical condition. XSG: The setting was secondary care. The economic study was conducted in the USA. XDD: No dates were reported in the paper. XDR: Discounting was not relevant since the costs were incurred during less than one year. The quantities and the costs were not analysed separately. The costs were considered from the perspective of the health care system. Therefore, only direct medical costs were included in the study. The total direct costs were disaggregated into those incurred while the patient was in hospital and those arising from treatment on an outpatient basis. The costs were estimated using actual data from a number of sources. Although no dates for the cost data were explicitly reported, it would appear that the sources were accessed in 1999. XMB: HRQL was measured using:the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q);a global measure of quality of life, which rated current health on a scale from 0 (death) to 100 (complete health); andquestions on disability days, that is, the number of days on which usual activities had been restricted and the number of days when the patient was confined to bed due to illness.These instruments and questions were administered during telephone interviews. XSD: The study was a 12-week, randomised, double-blind, double-dummy, parallel-group clinical trial, which was conducted at 21 sites in the USA. Of the entire sample, 78 patients were followed up for more than 21 days. Sixty-three of these 78 patients completed the baseline HRQL interviews. XSS: The effectiveness data were derived from a single study (see Other Publications of Related Interest). OI: The authors made no direct comparison between their results and those of other studies, although they did refer to other relevant studies. The authors recognised a number of limitations with their study. First, the selection of the sample for the economic study. Second, the lack of generalisability of the results to patients who were not hospitalised. Third, the collection of follow-up data using telephone interviews. The authors also acknowledged that the results were derived from a small sample over a relatively short follow-up period. The duration of the follow-up period is important given the need for long-term maintenance therapy for patients with bipolar disorder. The authors do not appear to have presented the study results selectively and their conclusions reflected the scope of the analysis. SCO: The rationale for the choice of the comparator was clear. The authors compared divalproex, an established treatment for acute mania, with a more recently approved alternative, olanzapine. You should decide if this is appropriate for your setting. VB: The instruments used to derive the health benefits were appropriate. Since the analysis of clinical and HRQL outcomes indicated that the two treatments were equivalent, the economic analysis concentrated on the costs. VC: The economic perspective adopted was that of the health care system and, therefore, the analysis was limited to the direct medical costs. It appears that all the relevant costs have been included in the analysis. However, it was unclear whether the costs of treating adverse events were included. The unit costs and the resources were not reported separately and the price year was not reported. Therefore, reflation exercises would not be possible. No statistical analysis of the quantities was performed. In addition, a sensitivity analysis was not undertaken. The authors acknowledged that the costs estimated in the trial might overstate those incurred in practice, owing to the inclusion of regular visits from health professionals in the trial protocol. VM: The effectiveness data were derived from a cohort study, which was part of a larger randomised controlled trial. The inclusion criteria for the economic analysis specified that the patients had to have at least one follow-up assessment. While this may have introduced some sampling selection biases, the authors found that there were no statistically significant differences in baseline variables between the entire sample and the sub-sample included in the economic study. As patients in the sample were hospitalised, the authors acknowledged that the study sample might not have been representative of the entire population of all patients (i.e. including those who were not hospitalised) who suffer from acute mania. Appropriate statistical analyses were undertaken (e.g. ANCOVA) to account for potential biases. XAE: The analyses of the clinical outcomes were based on the initial random assignment, intention to treat principles, and last observation carried forward. However, the economic analysis was based only on those who had at least one follow-up assessment. The primary health outcomes were the MRS from the SADS Change Version and the Hamilton Rating Scale for Depression (HAM-D). Differences between the treatments were evaluated using an analysis of covariance (ANCOVA) with treatment group and baseline score as covariates. XCL: There were no statistically significant differences in the MRS or HAM-D scores between the divalproex- and olanzapine-treated groups. XDI: Mental disorders. XFU: Supported by Abbott Laboratories. XLI: The costing was undertaken prospectively on the same sample of patients as that used in the effectiveness study. XOP: Zajecka JM, Weisler R, Sachs G, et al. A Comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder. Journal of Clinical Psychiatry 2002;63:1148-55. XRE: No statistically significant differences were found in MRS scores between the two groups at baseline and 3 weeks, or over the 12-week study period, (p>0.05).Similarly, the HAM-D scores were not statistically significantly different between the two groups at any follow-up period, (p>0.05).Adverse events occurred with a higher incidence in the olanzapine group than in the divalproex group. These included somnolence (47% versus 29%), weight gain (25% versus 10%), rhinitis (14% versus 3%), oedema (14% versus 0%), and slurred speech (7% versus 0%), (p<0.05 for all comparisons). No adverse events occurred more frequently in the divalproex group. XSM: Power calculations were not performed before the trial commenced. Post hoc estimates of statistical power to detect significant differences in the outcome measures were 20%. Eligible patients were screened within 3 days of randomisation. Randomisation to divalproex or olanzapine occurred at a ratio of 1:1. In total, 120 patients participated in the trial, 63 received divalproex and 57 received olanzapine. However, only patients with at least one follow-up assessment were included in the economic study. Therefore, the sample size for the economic study was reduced to 52 patients, of which 27 received divalproex and 25 olanzapine. XCO: No indirect costs were included in the analysis. XCU: US dollars ($). XSA: A statistical analysis of the costs was carried out using Wilcoxon rank-sum tests. XSY: No sensitivity analysis was carried out. XEB: There were no statistically significant differences between baseline and 6 or 12 weeks in the Q-LES-Q domains or global measure of quality of life, (p>0.1 for these comparisons). Likewise, there were no statistically significant differences between the groups in the mean number of restricted activity days, (p=0.78), or bed disability days, (p=0.38). XCR: The total outpatient costs (mean +/- standard deviation) were $541 (+/- 327) in the divalproex group and $1,080 (+/- 638) in the olanzapine group, (p=0.004).The emergency room costs were $60 (+/- 157) in the divalproex group and $23 (+/- 87) in the olanzapine group, (p=0.4).The physician costs were $73 (+/- 101) in the divalproex group and $79 (+/- 144) in the olanzapine group, (p=0.84).Other professional costs were $28 (+/- 52) in the divalproex group and $18 (+/- 31) in the olanzapine group, (p=0.74).The study drug costs were $358 (+/- 279) in the divalproex group and $924 (+/- 622) in the olanzapine group, (p=0.002).Other drug costs were $22 (+/- 31) in the divalproex group and $16 (+/- 34) in the olanzapine group, (p=0.20).The inpatient costs were $13,162 (+/- 8,693) in the divalproex group and $14,442 (+/- 16,594) in the olanzapine group, (p=0.73).The total medical costs were $13,703 (+/- 8,708) in the divalproex group and $15,180 (+/- 16,780) in the olanzapine group, (p=0.88). XCB: Not applicable. XAU: Given the comparable clinical and health-related quality of life (HRQL) outcomes between the two groups, the significant savings in outpatient costs for divalproex is meaningful for the clinical management of bipolar disorder and for the mental health system. CO1: United States XIM: The authors recommended that the economic findings in this paper should be confirmed in larger prospective, naturalistic studies with a longer follow-up period. KWO: Acute Disease; Adult; Ambulatory Care /economics /utilization; Anticonvulsants /therapeutic use; Antipsychotic Agents /therapeutic use; Benzodiazepines; Bipolar Disorder /diagnosis /drug therapy; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Health Care Costs; Health Services /economics /utilization; Health Status; Humans; Male; Pirenzepine /analogs & derivatives /therapeutic use; Psychiatric Status Rating Scales; Quality of Life; Treatment Outcome; Valproic Acid /therapeutic use XAC: 22003000658 XID: 30 Nov 2004 XLA: English XPR: 12716270 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22003000658 Record #9 %%%% TTL: Utilising survey data to inform public policy: comparison of the cost-effectiveness of treatment of ten mental disorders AUT: Andrews G, Issakidis C, Sanderson K, Corry J, Lapsley H XSO: British Journal of Psychiatry XYR: 2004 VOL: 184 PAG: 526-533 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: Optimal and routine ("current") treatments for 10 mental health disorders in Australia were assessed. The mental disorders considered were depression, dysthymia, bipolar disorder, panic disorder/agoraphobia, social phobia, generalised anxiety disorder (GAD), post-traumatic stress disorder (PTSD), harmful use of alcohol, alcohol dependence and schizophrenia. XTI: Treatment. XEC: Cost-utility analysis. XPA: The study population comprised all patients suffering from mental disorders in Australia. More specifically, the analysis included patients who had used mental health services and received treatments over a 1-year period for (at least) one of the mental disorders considered. These were depression, dysthymia, bipolar disorder (affective disorders), panic disorder/agoraphobia, social phobia, GAD, PTSD (anxiety disorders), harmful use of alcohol, alcohol dependence (alcohol use disorders) and schizophrenia. XSG: All health care settings providing treatment for the 10 mental disorders examined were included in the analysis. The economic study was conducted in Australia. XDD: The effectiveness evidence was derived from studies published between 2000 and 2003. The resources use data were derived from literature published between 1998 and 2003. Year 1997 prices were used. XDR: The direct costs consisted of all health service costs associated with service use and treatment for the patients' only or principal complaint, for the 10 mental disorders examined in the analysis. No further analysis of the costs was provided. The costs and the quantities were not reported separately. Resources used under current treatment were based on patient self-reports, derived from Australian national mental health surveys conducted between 2000 and 2002. Resources used under optimal treatment were based on literature published between 1998 and 2003. The unit costs for both public and private sector were derived from published sources. The total costs for optimal treatment were derived using modelling. All the costs were estimated for 1-year time horizon, therefore discounting was not necessary and was not carried out. All the costs were converted to 1997 prices. It is likely that further details of the costs are provided in the parent studies (see Other Publications of Related Interest). XMB: The benefits were expressed as the YLDs averted by current or optimal treatment. They were estimated using data from the Australian national mental health surveys. The YLDs observed were calculated as the prevalence of the only or principal complaint, weighted by the disability weighting associated with that disorder. The YLDs were adjusted for time spent symptomatic using the ratio between current and 12-month cases. The YLDs averted because of treatment were estimated from prevalent cases having received effective treatment. It was assumed that the degree of change in symptoms resulting from effective treatment (measured in effect size units) reflected the degree of change in disability weightings used in the YLD calculations. Health state preference values were adopted from a published study that reported values provided by general practitioners for vignettes of people with each mental health disorder. The total YLDs due to mental disorders in the absence of any treatment were the sum of YLDs observed plus YLDs averted because of treatment. XOA: The outcomes assessed were:the prevalence of schizophrenia, anxiety, affective and alcohol use disorders in Australia;the percentage of current coverage and effective current coverage related to each disorder; andthe burden of disease observed in the population under study.The true burden of each disorder, defined as the burden in the absence of treatment, was then calculated by adding the burden observed plus the burden averted by current treatment and coverage. Most of the results presented in the paper were a summary of findings already published in parental studies. Further details can be found elsewhere (see Other Publications of Related Interest). XSS: Not stated. XSS: The effectiveness data were derived from a review or synthesis of completed studies. CED: All data were based on Australian national mental health surveys. EST: A model was used to evaluate the cost-effectiveness of current and optimal treatment for mental disorders and the proportion of burden avertable by treatment. Optimal treatment was modelled using three scenarios. These were optimal treatment at current coverage (scenario 1), optimal treatment at optimal coverage (scenario 2), and optimal treatment at 100% coverage (scenario 3). Coverage was defined as the proportion of people having at least one consultation for a mental disorder. All scenarios were modelled for varying levels of severity for each mental disorder. Under scenario 1, severity levels were assumed to remain constant. Under scenario 2, optimal coverage was arbitrarily defined as 100% for schizophrenia, 70% for anxiety and affective disorders and for harmful use of alcohol, and 30% for alcohol dependence (the average coverage for all mental disorders was 67%). Severity levels were kept constant for those currently under treatment, but were varied for the "extra cases" in treatment under optimal coverage, to reflect the severity one would expect if those not currently in contact with services were covered. Under scenario 3, 100% coverage was assumed, keeping optimal treatment strategies constant and defining severity on the basis of that observed among all cases in current treatment. The time horizon was one year. OI: The authors did not compare their results with those of other studies. However, their results consisted of summaries and comparisons across findings of other parent studies. The issue of generalisability to other settings was addressed. The authors reported their results in full. However, they did not perform an incremental analysis, to demonstrate the additional total cost per YLD averted resulting from replacing current treatment by optimal treatment, or from increasing the level coverage; such an approach might have influenced the final conclusions. A number of further limitations of the study were reported. First, the short time horizon of the analysis, which might have underestimated the benefits of treatment in terms of burden averted. Second, the uncertainty in some parts of the analysis was reflected in wide CIs for the cost-effectiveness ratios. Finally, the method used to estimate the YLDs had not been validated. Nevertheless, the authors' conclusions reflected the scope of the analysis. SCO: The comparator of both current and optimal treatment was no treatment. Although this choice was not explicitly justified, it allowed the active value of treatment to be evaluated. VB: The estimation of benefits was modelled. The model used was appropriate for this purpose, as it allowed the burden averted by treatment to be evaluated for a variety of assumptions about clinical effectiveness and treatment coverage. The authors considered measures of benefit (i.e. YLD) that appear to have been relevant for the treatments evaluated. They also noted that the disability-adjusted life-years lost could not be assessed since the treatment intervention studies did not use death as an outcome. VC: The perspective of the study was that of the health service (public and private providers). It was likely that all categories of cost were included in the analysis, although the authors did not provide any cost details. Further information was probably provided in the parent studies (see Other Publications of Related Interest). Although the resources used were identified, the quantities were not reported, and neither were the unit costs. This may hinder the generalisability of the authors' results in other settings. One additional limitation of this approach was that the cost data were based on self-reported treatments. A sensitivity analysis was undertaken, but the results were not given. Discounting was not undertaken, which was appropriate as the costs were incurred during a time horizon of one year. The date to which the costs referred was reported, and this improves the reproducibility of the results. VM: The authors did not undertake a systematic review of the literature. In contrast, they chose to use data reported in two national population surveys in Australia. One limitation of this approach was that all the data were based on self-reported symptoms to establish diagnosis and burden associated with the disorders. However, the choice of the data source allowed the authors to draw conclusions on both the clinical and cost-effectiveness of treatments for mental disorders at a national level. XBC: The results of the primary studies were not combined. XBD: Not applicable, as the data were based on two national mental health surveys, each collecting data on different mental health disorders. XBM: Not stated. XBP: Two primary studies (national surveys) were included in the review. XBV: Not stated. XDI: Mental disorders; Behavior and behavior mechanisms; Disorders of environmental origin. XFU: Supported by a grant from the National Health and Medical Research Council of Australia and by a contract from the Australian Department of Health and Ageing. XOP: Andrews G, Sanderson K, Corry J, et al. Cost-effectiveness of current and optimal treatment for schizophrenia. British Journal of Psychiatry 2003;183:427-35.Corry J, Sanderson K, Issakidis C, et al. Evidence-based care for alcohol use disorders is affordable. Journal of Studies on Alcohol 2004;65:521-9.Issakidis C, Sanderson K, Corry J, et al. Modelling the population cost-effectiveness of current and evidence based optimal treatment for anxiety disorders. Psychological Medicine 2004;34:1-17.Sanderson K, Andrews G, Corry J, et al. Reducing the burden of affective disorders: is evidence based health care affordable? Journal of Affective Disorders 2003;77:109-25. XRR: The number of prevalent cases in Australia with the mental disorders examined was: depression 648,375; dysthymia 78,209; bipolar disorder 71,308; panic disorder/agoraphobia 175,994; social phobia 206,976; GAD 376,290; PTSD 327,071; harmful use of alcohol 251,911; alcohol dependence 227,431; and schizophrenia 39,048. The total number of patients suffering from any of these mental disorders was 2,402,613.The total burden associated with each mental disorder, expressed in number of years lived with disability (YLDs), was: depression 143,018; dysthymia 37,781; bipolar disorder 13,363; panic disorder/agoraphobia 25,338; social phobia 30,058; GAD 85,341; PTSD 60,810; harmful use of alcohol 5,304; alcohol dependence 43,439; and schizophrenia 28,671. The overall burden of mental disorders in the population was 473,123 YLDs.The coverage (% effective coverage) for each of the mental disorders was: depression 60.2% (31.7%); dysthymia 50.9% (33.3%); bipolar disorder 66.1% (46.2%); panic disorder/agoraphobia 39.1% (23.8%); social phobia 20.8% (6.7%); GAD 37.6% (20.5%); PTSD 39.5% (25.1%); harmful use of alcohol 8.1% (3.6%); alcohol dependence 13.6% (7.8%); and schizophrenia 100% (100%). The overall coverage was 39.5%, of which 22.8% was deemed effective. XCO: The indirect costs were not included in the analysis. XCU: Australian dollars (Aus$). XSA: The costs were presented deterministically. However, it was reported that a sensitivity analysis provided confidence intervals (CIs) around the total cost of treatment. The results of the sensitivity analysis were not reported. XSY: A sensitivity analysis was carried out to investigate the impact of variability in the data on the cost-effectiveness results. CIs around the costs, benefits and cost-effectiveness ratios were calculated. Univariate analyses assessed the impact of changing various investigator-modelled parameters on the cost-effectiveness estimates. In addition, multivariate stepwise linear regressions were conducted for each mental disorder examined, to identify the important contributors to variance around the cost-effectiveness ratios. XEB: The YLDs averted by current coverage/current treatment (% total YLDs due to mental disorders that were averted by treatment) were: depression 22,559 (16%); dysthymia 4,982 (13%); bipolar disorder 2,536 (19%); overall, all affective disorders 30,078 (15%); panic disorder/agoraphobia 2,375 (9%); social phobia 2,530 (8%); GAD 14,469 (17%); PTSD 6,687 (11%); overall, all anxiety disorders 26,059 (13%); harmful use of alcohol 95 (2%); alcohol dependence 650 (2%); overall, all alcohol use disorders 745 (2%); schizophrenia 3,774 (13%). The overall YLDs averted by current coverage/current treatment were 60,655 (13%).The YLDs averted by current coverage/optimal treatment were: depression 32,583 (23%); dysthymia 7,446 (20%); bipolar disorder 4,529 (34%); overall, all affective disorders 44,557 (23%); panic disorder/agoraphobia 3,304 (13%); social phobia 3,885 (13%); GAD 23,424 (27%); PTSD 9,489 (16%); overall, all anxiety disorders 40,101 (20%); harmful use of alcohol 191 (4%); alcohol dependence 2,061 (5%); overall, all alcohol use disorders 2,253 (5%); schizophrenia 6,217 (22%). The overall YLDs averted by current coverage/optimal treatment were 93,128 (20%).The YLDs averted by optimal coverage/optimal treatment were: depression 37,518 (26%); dysthymia 10,032 (27%); bipolar disorder 4,626 (35%); overall, all affective disorders 52,176 (27%); panic disorder/agoraphobia 5,244 (21%); social phobia 10,201 (34%); GAD 40,981 (48%); PTSD 14,358 (24%); overall, all anxiety disorders 70,784 (35%); harmful use of alcohol 1,059 (20%); alcohol dependence 4,537 (10%); overall, all alcohol use disorders 5,597 (11%); schizophrenia 6,217 (22%). The overall YLDs averted by optimal coverage/optimal treatment were 134,774 (28%).The YLDs averted by 100% coverage/ optimal treatment were: depression 48,239 (34%); dysthymia 14,105 (37%); bipolar disorder 5,372 (40%); overall, all affective disorders 67,715 (35%); panic disorder/agoraphobia 7,090 (28%); social phobia 14,798 (49%); GAD 57,213 (67%); PTSD 19,289 (32%); overall, all anxiety disorders 98,390 (49%); harmful use of alcohol 1,479 (28%); alcohol dependence 15,124 (35%); overall, all alcohol use disorders 16,603 (34%); schizophrenia 6,217 (22%). The overall YLDs averted by 100% coverage/optimal treatment were 188,926 (40%). The benefits were estimated for a time horizon of one year. XCR: The total costs (Aus$ million) associated with current coverage/current treatment were: depression Aus$483.7; dysthymia Aus$70.8; bipolar disorder Aus$60.9; all affective disorders Aus$615.5; panic disorder/agoraphobia Aus$81.7; social phobia Aus$43.6; GAD Aus$112.3; PTSD Aus$158.2; all anxiety disorders Aus$395.7; harmful use of alcohol Aus$9.2; alcohol dependence Aus$63.7; all alcohol use disorders Aus$72.9; schizophrenia Aus$739.9.The overall costs associated with current coverage/current treatment were Aus$1,824.0 million.The total costs (Aus$ million) associated with current coverage/optimal treatment were: depression Aus$341.3; dysthymia Aus$28.7; bipolar disorder Aus$108.4; all affective disorders Aus$478.4; panic disorder/agoraphobia Aus$65.4; social phobia Aus$33.1; GAD Aus$118.2; PTSD Aus$149.2; all anxiety disorders Aus$366.1; harmful use of alcohol Aus$1.7; alcohol dependence Aus$118.6; all alcohol use disorders Aus$120.3; schizophrenia Aus$668.2.The overall costs associated with current coverage/optimal treatment were Aus$1,633.1 million.The total costs (Aus$ million) associated with optimal coverage/optimal treatment were: depression Aus$375.5; dysthymia Aus$35.3; bipolar disorder Aus$114.8; all affective disorders Aus$525.7; panic disorder/agoraphobia Aus$112.8; social phobia Aus$110.7; GAD Aus$205.1; PTSD Aus$242.2; all anxiety disorders Aus$670.8; harmful use of alcohol Aus$14.6; alcohol dependence Aus$243.2; all alcohol use disorders Aus$257.8; schizophrenia Aus$668.2.The overall costs associated with optimal coverage/optimal treatment were Aus$2,122.5 million.The total costs associated with 100% coverage/optimal treatment were not calculated. XCB: The costs and benefits were combined in the form of cost-effectiveness ratios. These expressed the cost per YLD averted by current or optimal treatment compared with no treatment.The total cost/YLD averted by current coverage/current treatment was: depression Aus$21,442; dysthymia Aus$14,217; bipolar disorder Aus$24,031; all affective disorders Aus$20,463; panic disorder/agoraphobia Aus$34,389; social phobia Aus$17,218; GAD Aus$7,761; PTSD Aus$23,656; all anxiety disorders Aus$15,184; harmful use of alcohol Aus$96,813; alcohol dependence Aus$98,095; all alcohol use disorders Aus$97,932; schizophrenia Aus$196,070. The overall cost/YLD averted by current coverage/current treatment for all 10 mental disorders examined was Aus$30,072. In addition, 95% CIs around these cost-effectiveness ratios were provided.The total cost/YLD averted by current coverage/optimal treatment was: depression Aus$10,475; dysthymia Aus$3,858; bipolar disorder Aus$23,934; all affective disorders Aus$10,737; panic disorder/agoraphobia Aus$19,820; social phobia Aus$8,531; GAD Aus$5,048; PTSD Aus$15,728; all anxiety disorders Aus$9,130; harmful use of alcohol Aus$8,861; alcohol dependence Aus$57,542; all alcohol use disorders Aus$53,412; schizophrenia Aus$107,482. The overall cost/YLD averted by current coverage/optimal treatment for all mental disorders was Aus$17,536. The 95% CIs around these ratios were also provided.The total cost/YLD averted by optimal coverage/optimal treatment was: depression Aus$10,010; dysthymia Aus$3,517; bipolar disorder Aus$24,827; all affective disorders Aus$10,075; panic disorder/agoraphobia Aus$21,518; social phobia Aus$10,851; GAD Aus$5,004; PTSD Aus$16,867; all anxiety disorders Aus$9,476; harmful use of alcohol Aus$13,775; alcohol dependence Aus$53,603; all alcohol use disorders Aus$46,064; schizophrenia Aus$107,482. The overall cost/YLD averted by optimal coverage/optimal treatment for all mental disorders was Aus$15,748. The 95% CIs around these ratios were not provided.No cost-effectiveness ratios were calculated for 100% coverage/optimal treatment.The results of the univariate sensitivity analyses and regression analyses were not provided. However, they have been reported in the parental specific-disorder studies (see Other Publications of Related Interest). XAU: Optimal treatment would avert a greater proportion of the burden of mental disorders and, even though more comprehensive, would cost no more than current treatment. This is because of fewer inpatient stays and no use of treatments that generated costs without benefits. Optimal treatment for affective disorders, especially dysthymia, was cost-effective. In terms of anxiety disorders, even with perfect coverage and treatment, half of the associated burden would remain unavertable. The average cost per year lived with disability (YLD) averted for alcohol disorders and schizophrenia was high, especially for the latter. Even with 100% coverage and optimal treatment, 60% of the burden was still unavertable in the light of existing knowledge. Although coverage of some of the more efficient treatment should be extended, other factors justified the continued use of less efficient treatment for some disorders. CO1: Australia XIM: The authors recommended that the coverage of anxiety and affective disorders should be extended. They also recommended that clinicians be encouraged to practise evidence-based medicine, even if the budgetary and organisational requirements of implementation are considerable. They suggested that issues such as equity, need and societal demand, as well as efficiency, be given more consideration in light of their results when setting priorities for service delivery. In general, further research on both the prevention and the mechanisms of the mental disorders examined was recommended. KWO: Anxiety Disorders /economics /therapy; Australia; Bipolar Disorder /economics /therapy; Cost of Illness; Cost-Benefit Analysis /economics; Evidence-Based Medicine; Health Policy /economics; Health Surveys; Humans; Mental Disorders /economics /therapy; Mental Health Services /economics; Mood Disorders /economics /therapy; Psychoses, Alcoholic /economics /therapy; Schizophrenia /economics /therapy; Time Factors XAC: 22004008226 XID: 30 Jun 2005 XLA: English XPR: 15172947 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22004008226 Record #10 %%%% TTL: Modelling the treated course of schizophrenia: development of a discrete event simulation model AUT: Heeg B M, Buskens E, Knapp M, van Aalst G, Dries P J, de Haan L, van Hout B A XSO: PharmacoEconomics XYR: 2005 VOL: 23(Supplement 1) PAG: 17-33 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study examined unspecified methods to increase compliance (by 20%) with therapies for the treatment of schizophrenia. Initially, conventional antipsychotic medication was administered. This was switched to atypical antipsychotic drugs and, subsequently, to clozapine if the administered treatment was ineffective or the side effects were intolerable. XTI: Secondary prevention and treatment. XEC: Cost-effectiveness analysis. XPA: The target population comprised patients experiencing their second or third psychotic episode, who deteriorated over time, for whom the decision about potentially long-term medical therapy had been undertaken. First-time episode patients were excluded. XSG: The setting was both the community and secondary care. The economic study appears to have been carried out in the Netherlands and the UK. XDD: Some of the effectiveness and health care resource use data used in the model were derived from papers published between 1984 and 2003. The costs were reported in 2002 prices. XDR: The perspective adopted for the cost estimation was that of the UK health care services. The direct medical costs included medication, visits to a psychiatrist, and costs associated with residing in particular locations (i.e. community treatment, intense community treatment, staffed hostel or hospital). These were estimated at 2002 prices. The costs of medications were derived from the Drug Tariff 2002. The costs associated with residing in particular locations were derived from the Personal Social Services Research Unit Report. The unit costs were reported separately, although the quantities of resources used were generated by the model itself. The costs were modelled over a 5-year period and were discounted at a rate of 6%. The type of costs estimated were the average costs per patient. XMB: The number of relapses was used as the measure of benefit. This was discounted at a rate of 1.5% over the 5-year time horizon. Some other model outcomes reported in the paper were the total duration of psychosis, the time between relapses, the average Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores during relapse and between relapses, and the time on first-line treatment. XOA: The outcomes assessed were the probabilities of experiencing side effects (i.e. extrapyramidal symptoms, tardive dyskinesia, sedation, weight gain and agranulocytosis) with conventional therapy, atypical therapy and clozapine. XSS: Not reported. XSS: The effectiveness data were derived from a review of the literature, which appears to have been non-systematic. When data were unavailable, expert panels were used. CED: Not reported. EST: Discrete events simulation (DES) was used to model the costs and outcomes. The time horizon considered was 5 years. A Dutch expert panel was used to develop the concepts used in modelling, and the model was refined through group discussion and individual interviews. A hypothetical sample of 2,000 patients was randomly generated from the baseline distributions assigned to patient characteristics. The model was run 2,000 times for each simulation. OI: The authors compared their cost estimates with those from another study. They concluded that the fact that their own estimate was almost twice that of the other study might be accounted for by inflation and differing case severity. The issue of the generalisability of the results to other settings was not addressed. The authors highlighted a number of other limitations in their mode. First, the modelling of compliance (in reality compliance can take place in a variety of ways). Second, psychiatrists may switch therapies for several reasons. Third, the correlation between various side effects. Finally, the fact that severity can be measured along a range of dimensions. SCO: The authors considered current practice in the treatment of schizophrenia as the comparator for the economic analysis. They modelled the impact of an improvement in the patient's compliance. However, there were no details on how this improvement in compliance would be achieved, which introduces uncertainty into the validity of the intervention considered at analysis. VB: The summary measure of health benefit was specific for the type of disease and treatments considered at analysis. It was obtained through the modelling exercise and appears to have been appropriate. However, it does not enable the study results to be compared with those obtained for different interventions. The authors reported that there were no data about quality of life in relation to treatments for schizophrenia. VC: The cost perspective adopted was that of the UK health care service. Most of the important costs appear to have been included in the analysis. However, given that the intervention used to increase compliance was not identified in the study, the associated costs of increasing compliance do not appear to have been included in the costing, and this would bias the results of the cost estimation in favour of the situation of increased compliance. The unit costs (from published sources) and total costs (generated by the model and its parameters) were reported. Extensive sensitivity analyses of the costs were performed to examine variability in the model parameters, although the choice of the ranges used was not justified. The unit costs appear to have been treated as point estimates, with no sensitivity analysis provided. VM: The manner in which the estimation of effectiveness parameters was developed involved a review of the literature, which appears to have been non-systematic, and the use of two expert panels. One panel was involved in developing the conceptual model, while the other was involved in estimating the parameter values, both on the basis of personal experience and knowledge of the literature. It was difficult to comment on the validity of the estimates obtained from the review of the literature, as little information on the methods used to identify, select and assess the primary studies was given. The authors did not fully describe the process by which parameters were estimated from the expert panels, nor did they report the number of experts involved in the process. However, it appears to have involved an attempt to achieve expert consensus. The parameter values were tested using a sensitivity analysis, although it was not reported how the extreme values were selected. A limitation reported by the authors was that information obtained from experts is often anecdotal and decisions about how to treat patients are often taken after the consideration of a broad range of issues. A further limitation reported was that the data around treatment effectiveness often related to a short-term period. XBC: Not reported. XBD: Not reported. XBM: Not reported. XBP: Four studies appear to have been reviewed in order to obtain the model parameters exclusively derived from the review. XBV: Not reported. XCE: A UK expert panel populated the model's parameter values based on their own personal experience and their knowledge of the literature. All experts were asked to comment on the model structure, its assumptions, and the estimates of epidemiological and treatment patterns. XCF: The following parameters were estimated through the expert panel.The probability of being compliant between episodes when in community treatment (0.6 with conventional treatment, 0.65 with atypical treatment and 0.65 with clozapine),The probability of being compliant between episodes when in intense community treatment was 0.75 with conventional treatment, 0.8 with atypical treatment and 0.8 with clozapine.The probability of being compliant between episodes when in a staffed hostel was 0.65 with conventional treatment, 0.7 with atypical treatment and 0.7 with clozapine.The probability of being compliant between episodes when in hospital was 0.8 with conventional treatment, 0.85 with atypical treatment and 0.85 with clozapine.A further series of parameters were used to describe the probabilities of switching treatment due to adverse events (i.e. extrapyramidal symptoms, tardive dyskinesia, sedation, weight gain agranulocytosis and more than two relapses on treatment), and those of changing treatment when in community treatment, intense community treatment, staffed hostel or hospital for patients who presented risk, patients who could take care of themselves, patients who could moderately take care of themselves, and patients who could not take care of themselves. The full set of parameter values was provided in Table 1 of the paper. XDI: Mental disorders. XFU: Supported by Janssen Pharmaceutica, N.V., Belgium. XOP: Csernansky JG, Mahmoud R, Brenner R, the Risperidone-USA-79 Study Group. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346:16-22.Geddes J, Freemantle N, Harrison P, et al. Atypical antipsychotics in the treatment of schizophrenia: a systematic overview and meta-regression analysis. BMJ 2000;321:1371-6.Guest J, Cookson R. Cost of schizophrenia to UK society. An incident-based cost-of-illness model for the first 5 years following diagnosis. Pharmacoeconomics 1999;15:597-610. XRR: The probabilities of side effects with conventional therapy were 0.176 for extrapyramidal symptoms, 0.027 for tardive dyskinesia, 0.25 for sedation, 0.1 for weight gain and 0 for agranulocytosis.The probabilities of side effects with atypical therapy were 0.07 for extrapyramidal symptoms, 0.006 for tardive dyskinesia, 0.07 for sedation, 0.12 for weight gain and 0 for agranulocytosis.The probabilities of side effects with clozapine were 0 for extrapyramidal symptoms, 0 for tardive dyskinesia, 0 for sedation, 0 for weight gain and 0.01 for agranulocytosis. XCO: The indirect costs were not estimated. XCU: UK pounds sterling (). XSA: The examination of uncertainty was restricted to the sensitivity analysis. The unit costs were treated as point estimates. XSY: One-way sensitivity analyses addressed:the effect that atypical medication had on symptoms,the threshold level at which symptoms would result in harm,symptom severity,the costs in the various locations,the potential risk by gender to cause self-harm,the probabilities that medications would be switched,the time between relapses, andthe level of severity.A multi-way, probabilistic sensitivity analysis was also performed to evaluate second-order uncertainty. It was applied jointly to the above parameters as well as to compliance, excluding severity. No explicit justification was provided for the choice of the values used in the sensitivity analysis. The 95% confidence intervals (CIs) were reported for some of the results of the probabilistic sensitivity analysis. XEB: The average number of relapses would be 4.08 if compliance could be reduced by 20% versus 3.53 if compliance were not improved (resulting in a reduction of 0.55). If compliance could be improved by 20%, there would be a reduction of 0.44 years in the total duration of psychosis, the time between relapses would increase by 0.44 years, the symptom scores would be reduced both during relapses and in between relapses, and the time on first-line treatment would be increased by 2.93 months.None of the values used in the univariate sensitivity analysis had a substantial impact on the reduction in the number of relapses. The highest value was 0.61 when severity was assumed to be "non-severe", while the lowest was 0.48 when severity was assumed to be "very severe". The most influential parameter was the potential risk of causing harm. The results from the multivariate sensitivity analysis showed that the 95% CI for the increased number of relapses when compliance was improved was 0.04 to 0.99. XCR: If compliance could be increased by 20%, the average (discounted) cost per patient would be 99,073. For a situation with no improvement in compliance, the cost per patient would be 82,925 (the incremental discounted savings amounted to 16,147).When univariate sensitivity analyses were carried out, the costs were most sensitive to the potential risk of causing harm by gender, the probability of switching medication, and changes in the location costs. However, none of these variations from the base-case materially altered the implications of the model. The results of the multivariate sensitivity analysis showed that the 95% CI for the discounted cost-savings when compliance was improved was -39,821 to 274. XCB: The benefits and costs were not combined. XAU: The authors' conclusions related primarily to the modelling methodology (discrete events simulation, DES), which they argued offers an easier way of promoting the necessary dialogue with clinicians than Markov modelling (where the dialogue relates to the more alien notion of transition probabilities). In terms of the results of the model, the authors concluded that increasing compliance by 20% resulted in cost-savings that were not sensitive to the parameter variations that they had tested. CO1: Netherlands, United Kingdom XIM: The authors suggested that further research to quantify the issue of whether patients are able to take care of themselves, and how this would impact on the effectiveness of the treatments, could be worthwhile. The study presented several caveats that should be taken into consideration when interpreting the results. KWO: Adult; Antipsychotic Agents /economics /therapeutic use; Decision Making; Female; Humans; Male; Models, Economic; Schizophrenia /drug therapy /economics /therapy; Self Care /classification XAC: 22005008348 XID: 31 Aug 2006 XLA: English XPR: 16416759 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22005008348 Record #11 %%%% TTL: Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis AUT: De Graeve D, Smet A, Mehnert, Caleo S, Miadi-Fargier H, Mosqueda G J, Lecompte D, Peuskens J XSO: PharmacoEconomics XYR: 2005 VOL: 23(Supplement 1) PAG: 35-47 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study compared the following therapeutic strategies for patients with schizophrenia:first-line treatment with long-acting risperidone, 25 mg every 14 days (ambulatory care or hospital setting);depot haloperidol, 100 mg every 28 days (ambulatory care) or 125 mg every 28 days (hospital setting); andoral olanzapine, 10 mg daily. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised a hypothetical cohort of young schizophrenic patients treated for at least 1 year and whose disease had not been diagnosed for longer than 5 years. XSG: The study setting was secondary care. The economic study was carried out in Belgium. XDD: The effectiveness data were derived from a review of studies published in 2001 and 2002. The price year was 2003. XDR: The direct medical costs of the Belgian health care system were included in the analysis. Such costs were for hospitalisation (medication, medical supervision, laboratory tests and accommodation) and ambulatory care (physician visits, injections, medications and laboratory tests). The cost of treating extrapyramidal effects was added for all strategies. The unit costs and resource use quantities were reported separately. The resources consumed by stabilised and relapsed schizophrenic patients were generally derived from an 11-member expert panel of Belgian psychiatrists using a Delphi method. Unit cost data were derived from the National Institute for Sickness and Invalidity Insurance (INAMI) and the Ministry of Health. The authors reported that in Belgium, patient subsidy impacts on expenses incurred by the INAMI according to the proportion of patients with preferential reimbursement caused by low income (VIPO). Based on a previous study, the authors assumed that 47% of schizophrenic patients were classified as VIPO. Since the costs were incurred over a 2-year period, future costs were discounted at an annual rate of 3%. The study reported the mean costs. The price year was 2003. XMB: The measure of benefits used was the proportion of patients successfully treated. This was defined as those patients who responded to initial treatment and who had none to two episodes of clinical deterioration, without needing to change treatment, over the 2-year period. XOA: The outcome assessed was the relapse rate, which then allowed the authors to calculate transition probabilities at relevant time points. XSS: Not reported. XSS: The effectiveness data were derived from a review and synthesis of published studies and from estimates derived from an expert committee, which supplemented data from the literature. CED: The authors did not specify the study designs or other criteria for inclusion in the review, but the effectiveness data were based on a long-term, double-blind prospective trial and a non-randomised survey. EST: A decision analytic tree model consisting of three main branches (one for each treatment strategy) was created using TreeAge DATA software. Four different health states were considered for the model:clinical response, defined as non-relapse or non-rehospitalisation;clinical deterioration, defined as a state characterised by positive clinical symptoms, behavioural problems, suicidal ideation or extra pyramidal symptoms;inadequate response, similar to the clinical deterioration state, except that inadequate response could occur in the first period of each therapeutic option or after a period of clinical deterioration or inadequate response; andlong-term hospitalisation, which occurs after four therapeutic failures.The time horizon for the model was 2 years, which was divided into six periods of 4 months each. At the end of each period, patients experiencing an inadequate response or clinical deterioration could be switched to an alternative therapy. OI: The authors made appropriate comparisons of their findings with those from other studies conducted in Germany, Canada and the Netherlands which had found that long-acting risperidone was a cost-saving strategy. The issue of generalisability to other settings was partly addressed in the sensitivity analyses. The authors do not appear to have presented their results selectively, although a more detailed and thorough explanation on how transition probabilities were derived would have been desirable. The authors' conclusions would appear to reflect the scope of the analysis.The authors reported a number of further limitations to their model. First, the use of a decision model might have simplified a complex reality. Second, the data on compliance had to be assumed. Third, the patient population used in the study might be difficult to manage. Finally, the study did not include indirect costs such as productivity losses. SCO: The authors reported that the three interventions examined were clinically relevant options. You should decide if these interventions used in the treatment of schizophrenia are current practice in your own setting. VB: The estimation of benefits was modelled using a decision analytic tree model, which was appropriate for the study question. The measure used (proportion of patients successfully treated) could be useful in this case, but it limits the comparability with other economic evaluations in other health fields. The benefits do not appear to have been discounted. This was not appropriate as the costs were discounted, and for consistency benefits would also have to be discounted. VC: All the categories of cost relevant to the perspective adopted were included in the analysis. All major relevant costs appear to have been included in the analysis. The costs and the quantities were reported separately in the analysis, which will increase the generalisability of the authors' results. Resource use was mainly derived from an 11-member expert panel of Belgian psychiatrists using a Delphi method. The unit costs were derived using national tariffs. Limited one-way sensitivity analyses were undertaken by varying resource use and unit cost data. The costs were incurred over a 2-year period, thus the costs incurred in the second year were discounted. The price year was reported, which will aid any future inflation exercises. VM: The authors undertook a review of the literature, which resulted in a limited number of trials of antipsychotic treatments being identified. Using the results from two trials and opinion from an expert committee, made up of two psychiatrists and one health economist, the authors derived transition probabilities to populate their model. However, the authors did not report the results from the review of the literature and those derived from the expert committee separately. Consequently, it was unclear which results were derived from the literature and which were derived from opinion. The estimates were explored in a sensitivity analysis using appropriate ranges. XBC: The primary studies were not combined. XBD: The authors reported that there was good congruence of results between the two studies used to derive effectiveness data. XBM: Not reported. XBP: Two primary studies were included in the review. The effectiveness data on haloperidol were derived from a long-term double-blind, prospective study that compared risperidone and oral haloperidol (Csernansky et al. 2002, see ,Other Publications of Related Interest. below for bibliographic details). The effectiveness data on olanzapine and risperidone were derived from a non-randomised survey that compared the two drugs (Rabinowitz et al. 2001, see ,Other Publications of Related Interest- below for bibliographic details). XBV: Not reported. XCE: The effectiveness data derived from the literature were supplemented using the opinion of an expert panel. This expert panel comprised two psychiatrists and one health economist. XCF: The authors did not provide separate estimates of effectiveness based on those reported in the literature and those derived from experts. Therefore, the combined estimates of effectiveness have been presented in the ,Results of the Review- section. XDI: Mental disorders. XFU: None stated. XOP: Rabinowitz J, Lichtenberg P, Kaplan Z, et al. Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics. Am J Psychiatry 2001;158:266-9.Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346:16-22.Laux G, Heeg B, van Hout B, et al. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany. Pharmacoeconomics 2005;23 Suppl 1:49-61.Heeg BM, van Aalst G, van den Arend JJ, et al. A discrete events model of long-term outcomes and cost of treatment with long acting risperidone in schizophrenia. Value in Health 2003;6:515-6.Llorca PM, Miadi-Fargier H, Lancon C, et al. Cost-effectiveness of schizophrenic patient care strategies: impact of an atypical antipsychotic in a long-acting infection formulation. L'Encephale 2005;31:235-46. XRR: The authors did not report the relapse rate estimates derived from Kaplan-Meier analysis of the two studies. However, they did report the transition probabilities (response rates) used in the model, which were based on data derived from the two studies and expert opinion.The response rates were:for long-acting risperidone, 91% at 4 months, 95% at 8 months, 90% at 12 months, 99% at 16 and 20 months, and 100% at 24 months;for olanzapine, 82% at 4 months, 94% at 8 and 12 months, 99% at 16 months, 97% at 20 months, and 100% at 24 months; andfor haloperidol depot, 77% at 4 months, 84% at 8 months, 86% at 12 months, 93% at 16 months, 94% at 20 months, and 98% at 24 months. XCO: The indirect costs were not included. XCU: Euros (EUR). XSA: The costs were treated as point estimates (i.e. the data were deterministic). XSY: A series of one-way sensitivity analyses were undertaken. The parameters varied were the improvement in efficacy over oral risperidone associated with the long-acting injectable formulation of risperidone, the proportion of VIPO patients, the efficacy of depot haloperidol, and dose variations for long-acting risperidone and olanzapine. XEB: The proportion of successfully treated patients over the 2-year period was 82.70% for long-acting risperidone, 74.80% for olanzapine, and 57.30% for haloperidol depot. XCR: The mean costs incurred per patient over the 2-year period were EUR 16,406 for long-acting risperidone, EUR 17,074 for olanzapine, and EUR 21,779 for haloperidol depot. XCB: The costs and benefits were combined using a cost-effectiveness ratio (i.e. the cost per successfully treated patient). The average cost per successfully treated patient was EUR 19,839 for long-acting risperidone, EUR 22,826 for olanzapine, and EUR 38,008 for haloperidol depot. The costs and benefits were not combined using an incremental analysis, as long-acting risperidone was found to be both more effective and less expensive than olanzapine and haloperidol.The results of the sensitivity analyses confirmed the robustness of the model to wide variations in inputs: long-acting risperidone dominated both olanzapine and haloperidol. XAU: Long-acting risperidone represented a favourable first-line strategy for patients with schizophrenia requiring long-term maintenance treatment. CO1: Belgium XIM: The authors would appear to recommend the use of long-acting risperidone as a first-line treatment option for schizophrenia in Belgium. KWO: Antipsychotic Agents /administration & dosage /economics /therapeutic use; Belgium; Benzodiazepines /administration & dosage /economics /therapeutic use; Cost of Illness; Cost-Benefit Analysis /economics; Decision Trees; Delayed-Action Preparations; Economics, Pharmaceutical; Haloperidol /administration & dosage /economics /therapeutic use; Humans; Risperidone /administration & dosage /economics /therapeutic use; Schizophrenia /drug therapy XAC: 22005008349 XID: 03 Jun 2006 XLA: English XPR: 16416760 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22005008349 Record #12 %%%% DOI: 10.1007/s10597-005-6428-1 TTL: Does additional care provided by a consumer self-help group improve psychiatric outcome? A study in an Italian community-based psychiatric service AUT: Burti L, Amaddeo F, Ambrosi M, Bonetto C, Cristofalo D, Ruggeri M, Tansella M XSO: Community Mental Health Journal XYR: 2005 VOL: 41(6) PAG: 705-720 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study aimed to compare the collaboration between a community mental health service and a consumer organisation (i.e. a consumer self-help group) versus a community mental health service alone. XTI: Treatment and rehabilitation. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients who had at least one or more contacts with the South Verona CPS. XSG: The setting was the community and primary care. The economic analysis was carried out in Verona, Italy. XDD: The effectiveness and resource use data appear to have been collected since autumn 1997. The baseline period of the study was considered to be the trimester November 1999 to January 2000. Follow-up data were collected 2 years after baseline. The price year was not reported. XDR: Health service costs were included in the analysis. The categories considered were inpatient, sheltered accommodation, day-patient, outpatient and community costs. The latter (community costs) included visits made to patients' or relatives' home and to further community facilities. The resource use data were obtained from the South Verona Psychiatric Case Register, while the cost data were derived from an official source (the List of Costs per Unit). Operating costs for the self-help programme were not included in the analysis, although an estimate was quoted in the discussion. The costs were reported as the average cost per patient. The costs were not discounted; adjustments for inflation and the price year were not reported. XMB: The authors did not derive a summary measure of benefit in the economic analysis. In effect, a cost-consequences analysis was performed. XSD: The analysis was based on a cohort study. Two researchers blinded to the objectives and methods of the study collected the data. Data were collected for a 2-year period before baseline and for a 2-year follow-up period after baseline. It was reported that the follow-up data were standardised to represent an exact 2-year period. EST: The baseline characteristics of the patient groups were compared using either the chi-squared test (for categorical characteristics) or the Wilcoxon test (for continuous characteristics). Within each group, changes in outcomes between baseline and follow-up were analysed using the Wilcoxon test. All statistical analyses were performed using SPSS 11.0 software. OI: Since the authors did not compare their findings with those from other studies, it was not possible to determine the degree of agreement with other published studies. The authors do not appear to have presented their results selectively. Although the authors acknowledged that the study sample was not representative of the study population in terms of severity, they generalised their conclusions across all levels of severity. The authors reported further limitations to their study. First, patient groups differed in previous patterns of care, which might have introduced some bias into the results. Second, the patients' baseline assessment was not undertaken concurrently with the initiation of their participation in the self-group activities. SCO: It was unclear why the authors chose the comparator used since they did not justify their choice. You should decide if this represents a valid comparator in your own setting. VB: The authors did not derive a summary measure of benefit. In effect, a cost-consequences analysis was performed. VC: Although the perspective adopted in the economic analysis was not explicitly reported, it appears to have been that of the health care provider. The costs for a self-help programme were quoted in the discussion but were not included in the analysis; the authors stated that this omission is unlikely to have affected the results. The costs and resource use were reported separately as the average value per patient. The costs were derived from Italian sources, but no sensitivity analysis of the costs was performed. Discounting, adjustments for inflation, currency conversion and the price year were not reported. These issues may limit the interpretation of the findings. VM: The analysis was based on a cohort study. This type of study is usually associated with some limitations arising from the lack of random allocation of patients to the study groups. Thus, some selection bias might have affected the results. Marital status, education and occupation were significantly different between the groups and this might have biased the results. Appropriate statistical analyses were not undertaken to take account of potential biases and confounding factors. No sensitivity analyses were undertaken to account for variation in patient population. Power calculations were not reported. The authors acknowledged that the study was inadequately powered to detect various statistically significant differences between the groups. The evidence came from a single centre, which might not be representative of other institutions. The potential uncertainty in the clinical results was not addressed in the sensitivity analysis. These issues represent limitations to the internal validity of the findings and suggest that the effectiveness results should be treated with some caution. XAE: The primary health outcomes were:global functioning, as assessed using the Global Assessment of Functioning Scale;symptomatology, using the Brief Psychiatric Rating Scale (sub-scale for manic symptoms and negative symptoms);disability, using the Disability Assessment Schedule; andpatients' needs, using the Camberwell Assessment of Need.In addition, patient satisfaction with work and/or education was also evaluated using the Lancashire Quality of Life instrument. All the patients included in the study were accounted for in the analysis. However, differences at baseline (i.e. in marital status, education and occupation) were not adjusted for in the analysis. It was reported that all initially eligible patients (53 in the self-help group and 309 in the non self-help group) were also compared in terms of their baseline characteristics. However, adjustments for confounding factors were not performed. XCL: The analysis demonstrated that there were no significant differences between the two groups in terms of their clinical and social outcomes. XDI: Mental disorders; Behavior and behavior mechanisms. XFU: Supported by a grant from Regione del Veneto, Giunta Regionale, Venezia, Ricerca Sanitaria Applicata. XLI: The resource data were collected prospectively using the same sample of patients as that used in the effectiveness study. XRE: Comparisons across groups for differences between the baseline and follow-up periods demonstrated that there were no statistically significant differences in global functioning, symptomatology, disability and patient satisfaction with work and/or education.The mean number and severity of needs increased significantly at follow-up in the non self-help group, (p<0.01). There was no statistically significant change in the self-help group. XSM: The sample size was not determined in the planning phase of the study and power calculations were not performed retrospectively. No patients were reported to have refused to participate. The self-help group comprised patients who were members of the group and had joined in its activities for a 2-year period. In contrast, patients were included in the non self-help group only if they had never been in contact with the self-help group.Sixty-nine patients were selected for the self-help group. Of these, only 58 were considered eligible for the study (had complete outcome evaluations). It was reported that, at follow-up, three patients had died and another two could not be interviewed. Consequently, the self-help group comprised 53 eligible patients for inclusion in the study. Three hundred and nine patients fulfilled the inclusion criteria for the non self-help group. The initial patient groups were exactly matched by gender, diagnosis, living arrangements and clinical severity, after which a sample of 88 patients (44 in each group) was included in the study. XCO: Productivity losses were not included in the analysis. XCU: US dollars ($). Costs in the List of Costs per Unit were originally expressed in Italian Lire at 1996 prices. The conversion rate used and year were not reported. XSA: The costs and resource use data were reported using descriptive statistics, namely the mean, standard deviation (SD) and ranges. The authors used the Wilcoxon test to allow for within- and across-group comparisons between baseline and the end of the follow-up period. This was appropriate given that the data were highly skewed. XSY: The authors did not use any methods to allow for uncertainty. XEB: See the 'Effectiveness Results' section. XCR: The average total costs were reported per patient and were reported for two periods.For the self-help group, the total cost was $19,963 (SD=24,300; range: 401 to 100,702) at baseline and $17,029 (SD=20,523; range: 330 to 88,826) at the end of the 2-year follow-up period. The difference was statistically significant, (p=0.007).For the non self-help group, the total cost was $6,666 (SD=11,188; range: 74 to 53,218) at baseline and $8,890 (SD=13,401; range: 111 to 54,181) at the end of the 2-year follow-up period. The difference was not statistically significant.The authors reported that across groups, comparisons between baseline and follow-up total costs approximated statistical significance, (p=0.017). XCB: The costs and benefits were not combined. XAU: "The findings suggest that consumer participation may possibly enhance the effects of psychiatric treatment on outcome." CO1: Italy XIM: Based on the results of the analysis, the authors recommend that, as patient participation in self-help activities shows no statistically significant improvement in terms of social and clinical outcomes, self-help should be considered as an activity to enhance users' own resources and motivation for recovery, rather than as a module of psychiatric treatment or rehabilitation. The authors made no recommendations for further research. KWO: Adult; Aged; Case-Control Studies; Community Mental Health Centers /economics /utilization; Female; Health Care Costs; Hospitalization /statistics & numerical data; Humans; Interviews as Topic; Italy; Male; Mental Disorders /diagnosis /rehabilitation; Middle Aged; Mood Disorders /diagnosis /rehabilitation; Outcome and Process Assessment (Health Care); Registries; Schizophrenia /diagnosis /rehabilitation; Self-Help Groups /economics /utilization; Social Support; Somatoform Disorders /diagnosis /rehabilitation XAC: 22006007606 XID: 31 Jul 2007 XLA: English XPR: 16328584 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22006007606 Record #13 %%%% TTL: Cost-effectiveness analysis of schizophrenia relapse prevention: an economic evaluation of the ZEUS (Ziprasidone-Extended-Use-in-Schizophrenia) study in Spain AUT: Bernardo M, Azanza J R, Rubio-Terres C, Rejas J XSO: Clinical Drug Investigation XYR: 2006 VOL: 26(8) PAG: 447-457 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study examined the atypical antipsychotic ziprasidone (ZIP), in differing doses, for the treatment of schizophrenia. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The target population comprised Spanish adult patients with stable chronic schizophrenia. XSG: The setting was primary care. The economic study was carried out in Spain. XDD: The effectiveness and resource use evidence was drawn from the 52-week ZEUS trial, published in 2005. The price year was 2005. XDR: Discounting was not carried out since a one-year analysis was performed. The quantities and costs were analysed in terms of the proportions of patients requiring various resources and were presented in a disaggregated fashion. The costs included in the analysis were the acquisition costs of drugs and concomitant medications for treatment of symptoms associated with underlying disease, the cost of treating AEs related to study medication, and the cost of relapses requiring hospitalisation. The quantities were estimated on the basis of data collected in the ZEUS study. The drug costs were obtained from the database of proprietary medicinal products of the Spanish Board of Pharmacy, while other unit costs were obtained from a national database. Costs not included were those for resources scheduled in the clinical trial (assumed to be equivalent for all treatments), rescue medication (antipsychotic administered to patients assigned to placebo and who withdrew from the study), and direct non-health care costs (e.g. childcare or transport). The price year was 2005. XMB: The outcome measure used in the economic analysis was the schizophrenia relapses avoided. XSD: The ZEUS study was a randomised, double-blind, placebo-controlled clinical trial of 52 weeks in duration. It assessed the efficacy of ZIP at three doses. The method of randomisation, blinded assessment and loss to follow-up were not reported in the present study. XSS: The effectiveness data were derived from a single study. EST: A deterministic model was constructed in Microsoft Excel as a theoretical framework allowing simulations to be made of complex health care processes related to drugs. It was designed according to pre-established protocols, using estimations obtained from available data on the efficacy, toxicity and costs of the alternatives compared. The time horizon was one year. OI: The authors noted the results of other studies, but acknowledged that they were not comparable because most analyses compared ZIP with active comparators rather than placebo. The issue of generalisability to other settings was not addressed. The authors did not present their results selectively and their conclusions reflected the scope of the analysis. They did not justify their choice of a single study for the analysis, even though other clinical trials of ZIP existed.The authors acknowledged and reported further limitations to their study. In particular, they pointed out that a dose-dependent relationship was not established for the efficacy of ZIP in the ZEUS study, which makes interpretation of the results difficult since daily dose is an important factor in the final cost of the disease. Another limitation of the study was the use of a theoretical model (i.e. a simplified simulation of reality) based on a non-pragmatic clinical trial SCO: The authors did not provide an explicit justification for the choice of the comparator (placebo) but this may have been discussed in the publication of the clinical trial (Bagnall et al. 2005). Treatment guidelines in schizophrenia usually recommend active therapy with typical or atypical antipsychotics, therefore it is important to decide whether this comparator does represent current practice in your own setting. VB: The estimate of benefits (relapses avoided) was obtained directly from the effectiveness analysis. It was justified by being a major clinical objective as well as one of the determining factors in the greater costs of treating schizophrenia. VC: All the categories of cost relevant to the perspective adopted were included in the analysis. Some relevant costs were omitted because they arose from the trial protocol and were common to all comparators. This is unlikely to have affected the authors' conclusions. The costs and the quantities were reported separately, which will enhance the generalisability of the results. No statistical analysis of the quantities was performed. However, medication dosage and duration of hospital stay during relapse were varied in the sensitivity analysis. The unit costs were taken from national published sources. A sensitivity analysis of the prices was conducted. Discounting was unnecessary since all costs were incurred during one year. The price year was reported, which will aid any possible inflation exercises. VM: The analysis was based on a single, randomised controlled trial, which was appropriate for the study question. The study sample, patient groups and loss to follow-up were not described in this paper, nor was the basis of the effectiveness analysis (intention to treat or treatment completers only). In a study of 52 weeks' duration, which is relatively lengthy in schizophrenia trials, the loss to follow-up may have been significant. Consequently, the handling of the analysis could have had a substantial impact on the results. XAE: The primary end points were the rate of relapse and relapse-free time, calculated using survival analysis from the number of relapses observed with each intervention. The rate of relapse was used to calculate the probability and risk of relapse in a given period, using an actuarial analysis. Adverse events (AEs) were reported as rates of serious AEs and severe AEs. It was not stated whether the analysis of the clinical study was conducted on an intention to treat basis or for treatment completers only. The authors did not report the comparability of the patient groups at baseline. XCL: Given that there were statistically significant differences in efficacy between ZIP and placebo, a cost-effectiveness analysis was then performed. AEs were considered for their effects on costs only. XDI: Mental disorders. XFU: Supported by Pfizer Espana. XLI: The costing was carried out prospectively on the same sample of patients as that used in the effectiveness analysis. XOP: Bagnall AM, Lewis RA, Leitner ML. Ziprasidona para la esquizofrenia y la enfermedad mental severa (Revisin Cochrane traducida). En: La Biblioteca Cochrane Plus, 2005, Numero 3. Available from: URL: http://www.update-software.comPeiro S, Gomez G, Navarro M, et al. Length of stay and antipsychotic treatment costs of patients with acute psychosis admitted to hospital: description and associated factors. The Psychops study. Soc Psychiatry Psychiatr Epidemiol 2004;39:507-13. XRE: The probability of relapse requiring hospitalisation was 0.43 for ZIP 40 mg, 0.35 for 80 mg, 0.36 for 160 mg and 0.38 for the average dose (base-case), (p<0.001 in all cases, except for 40 mg with p<0.003), versus a probability of 0.77 with placebo.The proportion of patients with serious AEs was 3.95% for ZIP 40 mg, 0% for 80 mg, 0% for 160 mg and 1.36% for the average dose, versus 0% with placebo.The proportion with severe AEs was 13.16% for ZIP 40 mg, 6.94% for 80 mg, 2.82% for 160 mg and 7.74% for the average dose, versus 9.33% with placebo. XSM: The ZEUS study was reported in greater detail elsewhere (Bagnall et al. 2005, see 'Other Publications of Related Interest' below for bibliographic details). The study reported the results of a comparison between ZIP in daily doses of 40 mg (n=75), 80 mg (n=72) or 160 mg (n=71), versus placebo (n=75). XCO: The indirect costs were not included in the base-case analysis. In the sensitivity analysis, the authors estimated the indirect costs resulting from absenteeism from work that would be avoided with the intervention (by reducing hospitalisations). XCU: Euros (EUR). XSA: The costs were treated deterministically. XSY: In the base-case, average values for ZIP doses, resource use and probabilities of relapse were used. A simple univariate sensitivity analysis was carried out in which the following scenarios were evaluated:different doses of ZIP (40, 80, 160 and 240 mg/day);minimum and maximum (+/- 20%) unit costs for health care resources;estimated threshold level of the probability of relapse with ZIP at which the annual cost of preventing a relapse was equal to the minimum cost reported in the Psychosp study (Peiro et al. 2004, see 'Other Publications of Related Interest' below for bibliographic details);estimated threshold of number of hospital days at which the cost of preventing a relapse would be zero; andestimated indirect costs that would be avoided with ZIP.The ranges were derived from ranges and confidence intervals (CIs) given in the literature. XEB: The benefits over a one-year analysis were reported as the numbers-needed-to-treat (NNTs) to prevent a relapse and the NNTs to observe a relapse:for ZIP 40 mg, these were 2.9 (95% CI: 1.8 to 3.1) and 2.3 (95% CI: 2.0 to 2.8), respectively;for ZIP 80 mg, these were 2.3 (95% CI: 2.2 to 4.2) and 2.9 (95% CI: 2.4 to 3.7), respectively;for ZIP 160 mg, these were 2.4 (95% CI: 2.1 to 4.0) and 2.8 (95% CI: 2.3 to 3.5), respectively;for ZIP average dose, these were 2.6 (95% CI: 2.0 to 3.7) and 2.6 (95% CI: 2.2 to 3.3), respectively; andfor placebo, the NNT to observe a relapse was 1.3 (95% CI: 1.2 to 1.4).The side effects of treatment were considered in the economic analysis. XCR: The approximate annual cost per patient treated was EUR 2,724 with ZIP 40 mg, EUR 2,446 with 80 mg, EUR 3,100 with 160 mg and EUR 2,754 with the average dose, versus EUR 2,682 in the placebo group.Therefore, the incremental costs produced by ZIP were EUR 42 with the 40-mg dose, -EUR 236 (savings) with the 80-mg dose, EUR 418 with the 160-mg dose and EUR 72 with the average dose. XCB: The estimated benefits and costs were combined in an incremental cost-effectiveness ratio (ICER).The average annual incremental cost per relapse avoided was EUR 186 for the average dose of ZIP, ranging from approximately -EUR 557 (savings) for the 80-mg dose to EUR 1,015 for the 160-mg dose. These values were all lower than the minimum cost of a relapse (EUR 2,830).The daily dose of ZIP did not determine the annual cost per relapse avoided in a uniform manner because no relationship between the dose administered and the efficacy of ZIP in preventing a relapse was found.ZIP 240 mg/day resulted in an ICER of EUR 3,221 per relapse avoided.Minimum and maximum costs of health care resulted in large variation, changing the ICER to -EUR 234 (savings) and EUR 606, respectively.For the cost of preventing a relapse to be equal to the minimum in the Psychosp study (i.e. EUR 2,830), the probability of a relapse with ZIP would have to increase to 0.54. This is 11 to 19% higher than the rates seen in the ZEUS study (0.35 to 0.43).The duration of hospital stay only had to increase from a base-case value of 21.78 days to 22.96 days for the additional cost of ZIP to be zero in comparison with placebo.The estimated indirect cost-savings with ZIP were EUR 71 per patient. XAU: From the perspective of the Spanish National Health Service, the prevention of schizophrenia relapse with ziprasidone (ZIP) was cost-effective in comparison with no treatment. However, the base-case showed large quantitative variations in relation to most of the parameters examined in the sensitivity analysis. CO1: Spain XIM: The authors suggested that, based on data from a long (52-week) Spanish clinical trial, the treatment of patients with chronic schizophrenia with ZIP prevents a considerable number of relapses at a reasonable cost, thus producing cost-savings in Spain. KWO: Adult; Antipsychotic Agents /administration & dosage /economics /therapeutic use; Chronic Disease; Cost-Benefit Analysis /methods; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Models, Econometric; Piperazines /administration & dosage /economics /therapeutic use; Program Evaluation /methods; Recurrence; Reproducibility of Results; Schizophrenia /economics /prevention & control; Spain; Thiazoles /administration & dosage /economics /therapeutic use; Time Factors XAC: 22006001670 XID: 28 Feb 2007 XLA: English XPR: 17163277 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22006001670 Record #14 %%%% DOI: 10.1007/s10198-006-0347-0 TTL: A decision model to compare health care costs of olanzapine and risperidone treatment of schizophrenia in Germany AUT: Beard A M, Maciver F, Clouth J, Ruther E XSO: European Journal of Health Economics XYR: 2006 VOL: 7 PAG: 165-172 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study compared the use of olanzapine with risperidone in the treatment of patients with an established history of schizophrenia. XTI: Treatment. XEC: Cost-utility analysis. XPA: The study population comprised a hypothetical cohort of patients currently suffering from an acute episode of schizophrenia, and who were being considered for first-line treatment with a second-generation atypical antipsychotic. The patients were assumed to have a long-term history of relapsing schizophrenia and to have no other concurrent psychotic diagnoses or other significant health issues. In addition, the patients were assumed to have not received any form of previous treatment with atypical antipsychotics. XSG: The study setting was secondary care. The economic study was carried out in Germany. XDD: The effectiveness data were derived from studies published between 1996 and 2001. The price year was 2002. XDR: The direct costs to the health care system were included in the analysis. These included the costs of medications, inpatient hospitalisation, clinic visits (psychiatric, general practitioner, social psychiatric and outpatient), residential home care, residential home care with nursing support, sheltered accommodation, and the default costs of a suicide attempt.The resource use data were derived from a clinical focus group that comprised four experts (a health economist and three clinical psychiatrists/psychotherapists) with clinical and health economic experience of treating schizophrenia in Germany. Suicide-related costs were derived from an Italian study, as no data specific to Germany were found. Drug doses were based on recommended levels for Germany and an analysis of typical prescribing in Germany using Mediplus IMS data. The unit costs for drugs were derived from German cost data, while the unit costs for other resource use were derived from German health care system sources. Discounting was not relevant, as the costs were incurred during one year, and was therefore not performed. The price year was 2002. XMB: The health benefit measures used in the economic analysis were the number of quality-adjusted life-years (QALYs) gained. The utility values were derived from a published study (Revicki et al. 1996, see 'Other Publications of Related Interest' below for bibliographic details). The study used a standard gamble approach with clinician assessment. XOA: The outcomes assessed in the review were:the clinical response data, defined by a proportional improvement in the Positive and Negative Symptoms Scale (PANSS);the risk of acute relapse;the suicide risk; andthe utility values associated with different health states associated with schizophrenia. XSS: Not reported. XSS: The effectiveness data were derived from a review and synthesis of published data. CED: The authors reported that data for the model were drawn from pivotal clinical trials of atypical antipsychotics, which were generally based on cohorts of adult patients with schizophrenia who had Brief Psychiatric Rating Scale (BPRS) scores of at least 24. EST: The model structure was split into two distinct treatment phases. The first part of the model was a decision tree that reflected an initial 3-month period of acute treatment in which the treatment intent was aimed primarily at reducing the current acute symptoms and stabilising the patient. The second part of the model was a Markov model tracking the longer term treatment experience of the patients. This phase was a prolonged longer term preventive treatment aimed at preventing acute relapses. OI: The authors did not make appropriate comparisons of their findings with those from other studies. The issue of the generalisability to other settings was not addressed. The authors do not appear to have presented their results selectively. However, with such a small difference between the two treatment groups in terms of the benefits and costs, the authors should have performed more a thorough and extensive sensitivity analysis. For instance, they could have undertaken probabilistic sensitivity analyses to examine the overall uncertainty in the model parameters.The authors reported a number of further limitations to their study. First, only direct costs were included; other costs such as impacts on carers and lost productivity were not included. Second, the effectiveness data were derived from clinical trials with tightly defined inclusion criteria, which might limit the generalisability of the results. Finally, the authors assumed that treatment response data could be equally applied in both first- and second-line settings. SCO: The authors conducted a head-to-head comparison of two second-generation oral atypical antipsychotics (i.e. risperidone and olanzapine). Second-generation oral atypical antipsychotics have recently been recommended as first-line treatment for newly diagnosed patients with schizophrenia. You should consider if these two treatments are currently being used in your own setting. VB: The estimation of benefits was modelled using a two-part model. The model consisted of a decision tree and Markov model, both of which were appropriate for the study question. The authors provided adequate details of the structure of the model. VC: All the categories of cost relevant to the perspective adopted were included in the analysis. No major relevant costs appear to have been omitted. The costs and the quantities were not reported separately, which will limit the generalisability of the authors' results. Resource use was derived from an expert panel based on schizophrenia experts. The authors performed a limited sensitivity analysis on these assumptions, only the hospitalisation rate being varied. The unit costs were derived from published sources. No sensitivity analysis of the unit costs was performed. Discounting was unnecessary since all the costs were incurred during one year. The price year was reported, which will aid future inflation exercises. VM: The authors did not state that a systematic review of the literature had been undertaken to identify relevant research and minimise biases. They provided only limited details of the review undertaken. The authors used a single study to inform each individual parameter. In some instances the authors reported the reason for using a particular study over others, for example, the study was the most conservative or had the largest study sample. The authors performed a very limited sensitivity analysis of effectiveness data in that they only varied the annual relapse rates. A more extensive sensitivity analysis would have helped demonstrate the reliability of the results. XBC: The authors did not combine the results of the primary studies. The results from only one study were used to populate an individual model parameter. XBD: Not reported. XBM: Not reported. XBP: Approximately 8 primary studies were included in the review of the literature. XBV: Not reported. XDI: Mental disorders. XFU: None stated. XOP: Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for informationRevicki DA, Shakespeare A, Kind P. Preferences for schizophrenia-related health states: a comparison of patients, caregivers and psychiatrists. Int Clin Psychopharmacol 1996;11:101-8.Palmer CS, Revicki DA, Genduso LA, et al. A cost-effectiveness clinical decision analysis model for schizophrenia. Am J Manage Care 1998;4:345-55.Alexeyeva I, Mauskopf J, Earnshaw S, et al. Comparing olanzapine and ziprasidone in the treatment of schizophrenia: a case study in modeling. J Med Econ 2001;4:179-92. XRR: For patients treated with olanzapine, 53.0% achieved an improvement in PANSS scores of at least 30%, 36.8% achieved an improvement of at least 40%, and 21.7% achieved an improvement of at least 50%.For patients treated with risperidone, 43.6% achieved an improvement in PANSS scores of at least 30%, 26.7% achieved an improvement of at least 40%, and 12.1% achieved an improvement of at least 50%.The annual relapse rate during the first year of treatment was 19.7% with olanzapine and 23.4% with risperidone.The annual relapse rate after the first year of treatment was 9.4% with both olanzapine and risperidone.The suicide risk rate was 13.1% at acute episode.The suicide completion rates were set to 23%.The utility weights for the health states were 0.56 for acute symptoms as inpatient, 0.60 for acute symptoms as outpatient, and 0.83 for excellent function as outpatient. XCO: The indirect costs were not included. XCU: Euros (EUR). XSA: The costs were treated as point estimates (i.e. the data were deterministic). XSY: The authors undertook a series of one-way sensitivity analyses to investigate the stability of the base-case estimates. The authors varied the absolute difference in relapse rates between olanzapine and risperidone from 5% to 20%. They also varied the alternative hospital admission rates for patients during an acute episode of schizophrenia (range: 50 to 100%). XEB: The number of QALYs gained when using olanzapine over risperidone was 0.06 per 100 patients. XCR: The costs of treating 100 patients with risperidone were EUR 3,261,334 during the first year of treatment.The costs of treating 100 patients with olanzapine were EUR 3,226,028 during the first year of treatment. XCB: The costs and benefits were not combined as olanzapine was found to be both more effective and less costly than risperidone (i.e. it was dominant).The results of the sensitivity analysis showed that varying the absolute difference in relapse rate between 5 and 20% had no effect on the model results as, under all scenarios, olanzapine was still found to be dominant. In addition, olanzapine remained less costly than risperidone unless hospital admission rates dropped to just below 20%. XAU: The analysis suggested that first-line use of olanzapine has potential cost and clinical benefit advantages over first-line risperidone in atypical naive patients with a history of relapsing schizophrenia. CO1: Germany XIM: The authors reported that their model could be used to compare a wider set of treatment strategies involving other atypical antipsychotics. KWO: Antipsychotic Agents /economics /therapeutic use; Benzodiazepines /economics /therapeutic use; Decision Support Techniques; Germany; Health Care Costs; Hospitalization /economics; Humans; Quality-Adjusted Life Years; Recurrence; Risperidone /economics /therapeutic use; Schizophrenia /drug therapy /economics /prevention & control; Suicide /prevention & control; Treatment Outcome XAC: 22006008361 XID: 31 Mar 2007 XLA: English XPR: 16896764 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22006008361 Record #15 %%%% TTL: Cost-effectiveness analysis of ziprasidone versus haloperidol in sequential intramuscular/oral treatment of exacerbation of schizophrenia: economic subanalysis of the ZIMO trial AUT: Canas F, Perez-Sola V, Diaz S, Rejas J XSO: Clinical Drug Investigation XYR: 2007 VOL: 27(9) PAG: 633-645 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The present study compared ziprasidone treatment with haloperidol in sequential intramuscular/oral treatment for patients with exacerbation of schizophrenia. The study was based on the Ziprasidone Versus Haloperidol in Sequential IM/Oral Treatment (ZIMO) trial. The mean intramuscular doses were 32.1 mg/day for ziprasidone and 14.8 mg/day for haloperidol. Initial and final mean oral doses were, respectively, 113.9 and 137.2 mg/day for ziprasidone and 19 and 17 mg/day for haloperidol. Further details of the intervention strategies were described elsewhere (Perez et al. 2006, see 'Other Publications of Related Interest' below for bibliographic details). XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The population comprised patients with a schizophrenia exacerbation under conditions of standard medical practice. The patients included in this study were those who were assigned to treatment with haloperidol or ziprasidone and who took at least one dose of these drugs, and for whom information was available on both treatment effectiveness and consumption of resources whilst in hospital. XSG: The practice setting was inpatient care. The economic study was carried out in Spain. XDD: The effectiveness data came from the ZIMO study published in 2006. The resource use and cost data were derived from sources published between 2004 and 2005. The price year was 2005. XDR: The direct health care costs were based on the number of days of hospital stay, and the study medications and concomitant medications required for the treatment of acute schizophrenia exacerbations. The costs of hospital stay covered medical, nursing and other staff costs, room and catering, allocated common service costs and the costs of drug administration. The costs per day in hospital were taken from the published literature. Study drug and concomitant medications prices were from the Drug Product Catalogue, which equated to the hospital acquisition prices. For concomitant medication, the defined daily dose established by the World Health Organization was assigned to patients when information on administration route and dosage was lacking. The costs were adjusted for inflation using the Consumer Price Index. Discounting was not carried out because of the short-term time horizon. The price year was 2005. XMB: The measure of benefit used was that of patient responders (see 'Analysis of Effectiveness' section for definition). XSD: The analysis was based on the ZIMO study, a naturalistic, prospective multi-centre trial comparing the effectiveness and tolerability of oral and parenteral formulations of ziprasidone and haloperidol in patients with acute schizophrenia exacerbation under routine conditions of care (Perez et al. 2006). Though not reported explicitly in the paper, its naturalistic design implies that the intervention was individually decided by each provider, in a non-randomised way. XLI: The same patients represented the prospective source for both clinical and resource use data. OI: The findings of the analysis were well reported, using both cost-effectiveness acceptability curves and cost-effectiveness planes. The authors compared their findings with those from other studies and their results were generally in agreement. They also addressed the issue of the generalisability of their results to other settings in the limitations reported. One such limitation was a possible overestimation of the costs of concomitant medication, although this was probably not significant in relation to the conclusions. Furthermore, the evaluation was based on a secondary objective, namely the reduction of negative symptoms, instead of the total BPRS score which would have identified haloperidol as the dominant option. SCO: The comparator was justified and was intended to reflect routine practice in the authors' setting. However, readers should consider if this is an adequate comparator in their own settings. VB: The measure of health benefit chosen (percentage of responders with >= 30% and >= 50% reductions in negative symptoms in the BPRS) is context specific and can only be compared with other psychiatric studies (and not with other economic evaluations). In addition, some other aspects such as positive symptoms were not evaluated. Uncertainty analyses over effectiveness estimates were conducted and reported. VC: Relevant cost categories and their associated costs were taken into consideration. The resource quantities and the unit costs were not reported separately, which would make it difficult to rework the analysis for other settings. The price year, the sources of resource use and unit costs were adequately reported. In addition, sensitivity analyses were conducted to assess the robustness of the cost estimates used. VM: The analysis was based on the ZIMO study, a naturalistic, prospective multi-centre trial. However, no information about power and sample size calculations was reported; the reader may need to refer to the main clinical paper for these details. The authors stated some limitations to the generalisability arising from the unequal sample sizes. There was insufficient detail in this report about the parent trial to be able judge the adequacy of its internal validity, and the reader should refer to Perez et al. 2006 for further information. The statistical analysis and different analytical strategies were handled credibly, but limited details were reported. Given that this was a naturalistic non-randomised study, care should be taken in assessing whether the results were due solely to the intervention as other potential confounders could have been responsible. Although the two groups were comparable in most reported parameters, there was little detail of the adjustments method used. XAE: Effectiveness was defined as the percentage of responders at the end of the study to each of the sequential treatments analysed. A responder was defined as a patient showing a >= 30% reduction from baseline score on the Brief Psychiatric Rating Scale (BPRS) negative symptoms sub-scale. A secondary analysis was performed in which responders were defined as those patients with a >= 50% reduction. No blinding of the outcome assessment was reported. The time horizon of the evaluation was adjusted to the duration of treatment for acute schizophrenia exacerbation in the hospital psychiatric ward until discharge. Further details were explained elsewhere (Perez et al. 2006). The statistical analysis included a descriptive study with central tendency and dispersion parameters. The continuous variables were evaluated by an analysis of covariance, which adjusted for potential confounders. XCL: The results showed that ziprasidone had a greater effectiveness in treating negative symptoms of schizophrenia regardless of whether the effectiveness criterion was a BPRS negative symptoms sub-scale reduction of >= 30% or >= 50%. XDI: Mental disorders. XFU: Funded by a grant from Pfizer Espana. XOP: Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.Perez V, Gutierrez-Fraile M, Gutierrez-Casares JR, et al. ZIMO trial: effectiveness and tolerability of ziprasidone vs. haloperidol in sequential IM/oral treatment. Schizophrenia Research 2006;81:93-4. XRE: According to the effectiveness values obtained with the two treatments, a difference in effectiveness in favour of ziprasidone was observed in terms of the proportion of patients showing both >= 30% (15.3%; p=0.023) and >= 50% (15.4%; p=0.031) reductions in negative symptoms of the BPRS. XSM: A total of 325 patients who met the criteria (see 'Study Population') were included. Of these, 255 were treated sequentially with ziprasidone and 70 with haloperidol. The authors reported the baseline characteristics of the patients and stated that there were no statistically significant differences between the groups. The only difference in baseline score that was very close to statistical significance was the positive symptoms sub-scale. No other details of sample selection and power calculations were reported in this paper. XCO: Productivity costs were not included in the analysis, which was appropriate given the study perspective. XCU: Euro (EUR). XSA: The data were treated stochastically and a similar statistical approach to that described in the 'Analysis of Effectiveness' section was used. Measures of central tendency and variability were reported. The mean total cost and cost per responder with each treatment option were reported, along with their 95% confidence intervals (CIs). XSY: To estimate uncertainty around the incremental cost-effectiveness ratio, the quasi-95% intervals were calculated. In addition, bootstrapping techniques were used to calculate 95% CIs for effectiveness and costs, with a total of 2,000 additional items obtained via re-sampling. Cost-effectiveness planes, willingness-to-pay acceptability curves, and a threshold analysis to observe how variations affected the duration of hospital stay, were also reported. XEB: In the >= 30% reduction group, the percentage of responders was 71.0% (95% CI: 65.4 to 76.6) for ziprasidone and 55.7% (95% CI: 44.1 to 67.4) for haloperidol, (p=0.023), significantly favouring ziprasidone.In the >= 50% reduction group, the percentage of responders was 56.9% (95% CI: 50.8 to 62.9) for ziprasidone and 41.4% (95% CI: 29.8 to 53.8) for haloperidol, (p=0.031).The percentage of patients taking one or more concomitant drugs was 38.6% for the ziprasidone group and 30.2% for the haloperidol group. XCR: The mean total cost per patient was EUR 3,582 (95% CI: 3,226 to 3,937) for ziprasidone and EUR 2,953 (95% CI: 2,471 to 3,436) for haloperidol, (p=0.039). XCB: The incremental cost for ziprasidone per additional responder was EUR 4,105 (95% CI: 113 to 51,864) for a reduction of >= 30% in BPRS negative symptoms and EUR 4,078 (95% CI: 376 to 51,213) for a reduction of >= 50%. The incremental cost-effectiveness ratios (ICERs) calculated using bootstrapping techniques were EUR 4,095 (95% CI: -130 to 22,231) and EUR 3,994 (95% CI: -305 to 21,583), respectively.The cost-effectiveness plane of the re-samplings showed that most of the ICERs fell within the upper right quadrant, corresponding to greater effectiveness with higher cost. The acceptability curves showed ICER cut-off points for a 95% acceptance probability level of EUR 13,891 for a reduction of >= 30% in symptoms and EUR 13,884 for a reduction of >= 50%. XAU: The results of the analysis showed that the greater cost associated with the use of ziprasidone was offset by its greater effectiveness compared with haloperidol in treating the negative symptoms of schizophrenia, resulting in a lesser cost per responder. Therefore, the authors considered that the results, and the potential impact of relief of the negative symptoms of schizophrenia at both economic and social levels, showed that sequential intramuscular/oral treatment with ziprasidone is a cost-effective option in comparison with haloperidol. CO1: Spain XIM: As the authors reported, this study was aimed at evaluating only the negative symptoms of schizophrenia. It would probably have shown greater benefits if a societal perspective had been contemplated. This would have enabled a more accurate capture and costing of the true burden of negative symptoms of schizophrenia on the patient's and family's daily life. KWO: Administration, Oral; Adult; Antipsychotic Agents /administration & dosage /economics; Brief Psychiatric Rating Scale; Cost of Illness; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Female; Haloperidol /administration & dosage /economics; Hospital Costs; Humans; Injections, Intramuscular; Length of Stay /economics; Male; Piperazines /administration & dosage /economics; Quality of Life; Research Design; Schizophrenia /drug therapy /economics; Spain; Thiazoles /administration & dosage /economics; Treatment Outcome XAC: 22007001989 XID: 31 Mar 2008 XLA: English XPR: 17705572 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22007001989 Record #16 %%%% TTL: The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron, ondansetron and dolasetron AUT: Paech M J, Rucklidge M W, Banks S L, Gurrin L C, Orlikowski C E P, Pavy T J XSO: Anaesthesia and Intensive Care XYR: 2003 VOL: 31(1) PAG: 11-17 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of tropisetron 2 mg at induction, ondansetron 4 mg at induction, and dolasetron 12.5 mg at the end of surgery to prevent postoperative nausea and vomiting (PONV) after major open abdominal gynaecological or gynaecological oncological surgery. Vomiting occurring more than 10 minutes after arrival in the recovery room was treated with intramuscular prochlorperazine (12.5 mg), while intravenous droperidol (1 mg) was given if prochlorperazine was ineffective one hour after administration. XTI: Secondary prevention. XEC: Cost-effectiveness analysis. XPA: The study population comprised women undergoing major open abdominal gynaecological or gynaecological oncological surgery. The exclusion criteria were preoperative nausea, the use of anti-emetics, and contraindications to nonsteroidal anti-inflammatory or epidural anaesthesia. Patients in whom an open procedure was not performed were excluded, as were those who underwent unplanned bowel surgery. XSG: The setting was secondary care. The economic analysis appears to have been conducted in Australia. XDD: The dates to which the effectiveness, resource use and unit cost data related were not reported. The price year was not given. XDR: The cost/resource boundary of the study was not stated, although it appears to have been that of the hospital. The direct costs considered in the economic analysis included the costs for emesis clean up, rescue anti-emetic dosing and the acquisition costs of an ampoule of the drug under investigation. The unit costs and the quantities of resources used for each group were provided separately. The drug costs were based on acquisition costs rather than patient charges. The cost data appear to have been derived from the study institution's data, although the authors did not clearly report the sources used to collect the resource use and unit cost data. The price year was not reported. Discounting was not relevant as the costs were incurred during a short timeframe. The estimated costs were the average costs per patient. XMB: No summary measure of benefit was used in the economic analysis since the effectiveness analysis showed that the three groups were comparable in terms of the clinical outcomes. The authors reported that a cost-minimisation analysis was carried out. XSD: The study was a double-blind, randomised clinical trial that appears to have been conducted in a single centre. The patients were randomly allocated to the study groups by means of a computer-derived sequence in blinded envelopes. The study drug administered was known only to the attending anaesthetist, who took no part in the collection of subsequent data. The drug was administrated diluted with normal saline to a 4-mL volume in all patients. The patients were followed up for 24 hours, with assessments performed at arrival in the recovery room to 30 minutes later, and from then until 2, 6, 12, 18 and 24 hours. No loss to follow-up was reported. XSS: The effectiveness data were derived from a single study. OI: The authors pointed out that, overall, their findings confirmed those from other studies. However, the generalisability of the results to other setting was not discussed. The study enrolled women undergoing major gynaecological surgery and this was reflected in the authors' conclusions. The authors do not appear to have reported their results selectively. They did not report any limitations of their study. SCO: The authors justified their choice of the comparators by stating that tropisetron, ondansetron and dolasetron were currently available in Australia for the treatment of PONV. You should consider whether these are widely used health technologies in your own setting. VB: No summary benefit measure was used in the economic analysis because the results obtained for the clinical outcomes were not statistically significantly different among the three procedures. Therefore, the authors carried out a cost-minimisation analysis. The reader is thus referred to the comments in the 'Validity of estimate of measure of effectiveness' field (above). VC: Although the perspective adopted was not explicitly reported, the cost categories included would appear to relate to the hospital. The unit costs and the resource quantities were reported separately, and the methods used to evaluate the costs and quantities of resources were described. However, the sources used to obtain quantity and cost data were not reported, and the price year was not stated. Statistical analyses of the costs were not carried out. These facts may limit the validity and the generalisability of the study findings. VM: The effectiveness results are likely to be internally valid because of the randomised nature of the study design and the power analysis performed. The method used to randomly allocate the patients to the study groups was reported and appears to have been appropriate. Moreover, it appears that appropriate masking of the interventions to the patients and investigators has been performed. The study groups were comparable in terms of their demographics and baseline characteristics. The study sample was not shown to be representative of the study population. Appropriate statistical analyses were performed to ensure the accuracy of the comparison. XAE: Although not explicitly stated, it appears that the basis for the analysis of the clinical study was intention to treat. The health outcomes used in the analysis were:the incidence and severity of vomiting and nausea during the first 24 hours, and up to 2 hours, from 2 to 6 hours, from 6 to 12 hours, from 12 to 18 hours, and from 18 to 24 hours;the number of anti-emetic doses administered; andthe patients' assessment of control of PONV.Visual analogue scales (ranging from 0 to 100) were used to assess the severity of nausea (100 being the worst possible outcome) and patient satisfaction (100 being the best possible outcome). The study groups were well balanced in terms of the patient demographics and baseline characteristics (e.g. age, weight, history of PONV, history of motion sickness, prior surgery). XCL: No significant differences were observed among the three groups in terms of effectiveness during the first 24 hours after major gynaecological surgery. XDI: Female genital diseases and pregnancy complications; Surgical procedures, operative; Digestive system diseases. XFU: None stated. XLI: The costing was performed prospectively on the same patient sample as that used in the effectiveness analysis. XOP: Figueredo E, Canosa L. Prophylactic ondansetron for post-operative emesis: meta-analysis of its effectiveness in patients with and without a previous history of motion sickness. European Journal of Anaesthesiology 1999;16:556-64.Naguib M, el Bakry AK, Koshim MH, et al. Prophylactic antiemetic therapy with ondansetron, tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind comparison with placebo. Canadian Journal of Anaesthesiology 1996;43:226-31.Pueyo FJ, Carrascosa F, Lopez L, et al. Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting. Anesthesia and Analgesia 1996;83:117-22.Tramer MR, Phillips C, Reynolds DJ, et al. Cost-effectiveness of ondansetron for postoperative nausea and vomiting. Anaesthesia 1999;54:226-34.Zarate, E, Watcha MF, White PF, et al. A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis. Anesthesia and Analgesia 2000;90:1352-8. XRE: The results among the tropisetron (T), ondansetron (O) and droperidol (D) groups, respectively, were as follows.The incidences of vomiting during the first 24 hours were 57% (T), 75% (O) and 72.5% (D), (p=0.18).The incidences of vomiting in the recovery room to 30 minutes later were 28.6% (T), 36.1% (O) and 22.5% (D), (p=0.42).The incidences of vomiting in the recovery room up to 2 hours were 22% (T), 25% (O) and 17.5% (D), (p=0.72).The incidences of vomiting in the recovery room from 2 to 6 hours were 11.9% (T), 11.1% (O) and 17.5% (D), (p=0.67).The incidences of vomiting in the recovery room from 6 to 12 hours were 14.3% (T), 13.9% (O) and 15.4% (D), (p=0.98).The incidences of vomiting in the recovery room from 12 to 18 hours were 14.3% (T), 22.2% (O) and 27.5% (D), (p=0.34).The incidences of vomiting in the recovery room from 18 to 24 hours were 28.6% (T), 47.2% (O) and 35.0% (D), (p=0.23).The percentages of patients with complete response were 23.8% (T), 16.7% (O) and 20.0% (D), (p=0.74).The median numbers of anti-emetic doses administered were 1 (interquartile range, IQR: 0 - 2) (T), 1 (IQR: 0 - 2) (O) and 1 (IQR: 0 - 2.5) (D), (p=0.82).The percentages of patients for whom the nausea score was equal to zero (i.e. best possible outcome) were 29.3% (T), 33.3% (O) and 25.0% (D), (p=0.73).The median overall nausea scores were 20 (IQR: 0 - 31) (T), 20 (IQR: 0 - 45) (O) and 14.5 (IQR: 2 - 47.5) (D), (p=0.99).The median worst nausea scores up to 2 hours were 0 (IQR: 0 - 29) (T), 0 (IQR: 0 - 30) (O) and 0 (IQR: 0 - 36) (D), (p=0.80).The median worst nausea scores from 2 to 6 hours were 0 (IQR: 0 - 9) (T), 0 (IQR: 0 - 3) (O) and 0 (IQR: 0 - 20) (D), (p=0.63).The median worst nausea scores from 6 to 12 hours were 0 (IQR: 0 - 0) (T), 0 (IQR: 0 - 0) (O) and 0 (IQR: 0 - 0) (D), (p=0.75).The median worst nausea scores from 12 to 18 hours were 0 (IQR: 0 - 3) (T), 0 (IQR: 0 - 50) (O) and 8.5 (IQR: 0 - 65) (D), (p=0.02).The median worst nausea scores from 18 to 24 hours were 10 (IQR: 0 - 61.5) (T), 24.5 (IQR: 0 - 61.5) (O) and 18 (IQR: 0 - 64) (D), (p=0.46).The median satisfaction with control of PONV were 100 (IQR: 90 - 100) (T), 97.5 (IQR: 80 - 100) (O) and 99.5 (IQR: 78 - 100) (D), (p=0.46). XSM: Sample size calculations indicated that 40 patients per group were required to demonstrate a reduction in the incidence of vomiting of 50% in the first 24 hours by tropisetron or dolasetron, compared with ondansetron (90% power and a significance level of 0.05). The authors did not report the method used to select the sample. Of the 120 eligible patients, two were excluded from the ondansetron group (one did not undergo surgery, while the other was transferred to an intensive care unit postoperatively). A total of 118 patients were assigned randomly to three study group. The tropisetron group comprised 42 patients, the dolasetron group 40 patients, and the ondansetron group 36 patients. The authors did not report any evidence that the study sample was representative of the study population. XCO: The indirect costs were not included. XCU: Australian dollars (Aus$). XSA: The costs were treated deterministically. XSY: Sensitivity analyses were not performed. XEB: See the 'Effectiveness Results' section. XCR: The estimated costs per patient were $17.15 in the tropisetron group, $23.40 in the ondansetron group and $21.40 in the dolasetron group. XCB: A synthesis of the costs and benefits was not relevant since a cost-minimisation analysis was carried out. XAU: The risk of postoperative nausea and vomiting (PONV) remained high in this setting despite prophylaxis with 5-hydroxytryptamine3 (5-HT3) receptor antagonists. Similar efficacy and no clinically relevant side effects were shown in the study. The choice between the agents studied should be based on the lowest available acquisition cost. CO1: Australia XIM: The authors recommended choosing the least expensive 5-HT3 antagonist drug for PONV prophylaxis. KWO: Antiemetics /economics /therapeutic use; Cost-Benefit Analysis; Double-Blind Method; Female; Humans; Indoles /therapeutic use; Middle Aged; Ondansetron /therapeutic use; Patient Satisfaction; Postoperative Nausea and Vomiting /drug therapy; Quinolizines /therapeutic use; Serotonin Antagonists /economics /therapeutic use XAC: 22003000519 XID: 30 Sep 2005 XLA: English XPR: 12635388 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22003000519 Record #17 %%%% TTL: Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost AUT: Mortimer A, Williams P, Meddis D XSO: Journal of International Medical Research XYR: 2003 VOL: 31(3) PAG: 188-196 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of atypical antipsychotics in schizophrenia. Olanzapine, risperidone and ziprasidone were compared with quetiapine. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised outpatients with schizophrenia who were taking oral conventional antipsychotics. XSG: The setting was secondary care. The study was carried out in the UK. XDD: The effectiveness data were derived from a review of published studies conducted in the past 20 years. Literature data were supplemented by expert opinion, the dates of which were not provided. The cost data for the US were obtained from two studies published in 1996 and 2001, while the cost data for the UK were obtained from another study published in 2000. The price year was not reported. XDR: The resources and the quantities were not reported separately. The direct costs of the hospital were included in the analysis. For the US-based costs, the authors derived their cost data from two studies (see Other Publications of Related Interest). One study (Glazer and Ereshefsky) built an economic model of outpatient antipsychotic therapy in schizophrenic patients who had been admitted to hospital numerous times in order to estimate the 1-year direct costs. The other study (Rosenheck et al.) estimated the average cost of hospitalising a veteran administration patient on atypical antipsychotics. For the UK-based costs the authors derived their cost data from a study by Almond and O'Donnell (see Other Publications of Related Interest), who used a Markov model to compare the 5-year costs of olanzapine, risperidone and haloperidol in the treatment of schizophrenia in the UK. Discounting was unnecessary, as all the costs were incurred during one year, and was not conducted. The study reported the incremental costs of olanzapine, risperidone and ziprasidone over quetiapine. The price year was not reported. XMB: No summary benefit measure was used in the economic analysis. A cost-consequences approach was therefore adopted. XOA: The outcomes assessed in the review were:the non-compliance and relapse rates observed when there was an abrupt withdrawal of antipsychotic medication,the rate of recovered patients continuing treatment with atypical antipsychotics, andthe relapse rates linked to a particular treatment period. XSS: MEDLINE, EMBASE and PsycINFO were searched for primary studies. XSS: The evidence for the final outcomes was derived from a review of published studies and reviews. It was supplemented by a two-round Delphi study, in which a panel of 25 experts on schizophrenia assessed the impact of different side effect profiles on non-compliance. CED: Longitudinal observational studies, carried out in North America, Europe and Australasia, of outpatients with schizophrenia who were taking oral conventional antipsychotics, and which reported time-specific non-compliance rates, were included in the review. EST: A state-transition model was used to represent the relationship between compliance and relapse over a 1-year period following recovery from an episode of schizophrenia. This technique involved identifying clinically important events and defining them as health states. The model incorporated three such states, "well, compliant" (starting state), "well, not compliant" and "relapsed". A theoretical cohort of patients then moved cyclically from one health state to another, in cycles set at the end of the month, for one year. To allow for the possibility that the probabilities of becoming not compliant and/or relapsing vary over time, Weibull survival distributions were fitted to the relevant data for each of the transition probabilities. OI: The authors did not compare their findings with those from other studies. The issue of generalisability to other settings was not addressed, further hampering the generalisability of the authors' results. The authors do not seem to have presented their results selectively. The authors' conclusions reflect the scope of the analysis. The authors reported no further limitations to their study. SCO: The choice of quetiapine as the comparator was not explicitly justified, although it would appear to be one of the four atypical antipsychotics currently being prescribed. Thus, it represented common practice in the authors' setting. You should decide if the comparator represents current practice in your own setting. VB: The authors did not derive a summary measure of health benefit. The analysis was therefore categorised as a cost-consequences analysis. VC: Since the cost data were derived and combined from several studies, and the authors gave very few details of which costs had been included, it is not possible to say whether all the categories of cost and all relevant costs were included in the analysis. However, the authors did point out that the per patient cost of managing treatment-induced side effects was ignored in the model, as it was assumed to be the same for each of the four atypical antipsychotics studied. Therefore, it is unlikely that such an omission will have affected the authors' conclusions. The costs and the quantities were not reported separately and the price year was not reported. These two limitations weaken the generalisability of the results and hinder reflation exercises to other settings. The incremental costs were presented with their respective 95% CIs and 99% CIs, thus acknowledging uncertainty in the costs. Discounting was unnecessary, as all the costs were incurred in one year, and was not performed. XCF: The experts concluded the following:the estimated non-compliance rates for all atypical antipsychotics profiles at 3, 6 and 12 months were better than those derived from the literature for conventional antipsychotics;the estimated non-compliance rates of quetiapine and ziprasidone were practically equal;the non-compliance rates based on the profiles of olanzapine and risperidone were greater than those based on the profiles of quetiapine and ziprasidone;the difference between the two pairs (olanzapine, risperidone and quetiapine, ziprasidone) increased with the duration of treatment. XDI: Mental disorders. XFU: Supported by AstraZeneca. XOP: Lindstrom E, Bingefors K. Patient compliance with drug therapy in schizophrenia. Pharmacoeconomics 2000;18:105-24.Glazer W, Ereshefsky L. A pharmacoeconomic model for outpatient antipsychotic therapy in "revolving door" schizophrenic patients. Journal of Clinical Psychiatry 1996;57:337-45.Rosenbeck R, Leslie D, Sernyak M. From clinical trials to real-world practice: use of antipsychotic medication nationally in the department of Veteran Affairs. Medical Care 2001:39;302-8.Almond S, O'Donnell O. Cost analysis of the treatment of schizophrenia in the UK. Pharmacoeconomics 2000;17:383-9. VM: The authors did not state that a systematic review of the literature had been undertaken, reporting only that a review using three search engines had found 32 publications. However, even if a systematic review was not performed to identify relevant research and minimise biases, the review undertaken was quite thorough. Three search engines were used to identify relevant studies carried out in North America, Europe and Australasia within the past 20 years. Data from these 32 studies were then supplemented with data from 2 systematic reviews. Survival analysis methods were used to summarise the data and estimate non-compliance rates. However, this method was not reported clearly, and it would appear that no weighting scheme was applied to reflect differences in sample sizes. Even though an investigation of differences between the primary studies was not reported, the inclusion criteria for entry into the review were fairly narrow (longitudinal observational studies of outpatients with schizophrenia who were taking oral conventional antipsychotics, which reported a time-specific non-compliance rate). Thus, any differences between the primary studies should not have greatly affected the estimate of effectiveness.The data derived from the literature review were supplemented by expert opinion. A Delphi panel of 25 leading European and North American experts in the field was assembled to derive the impact of different side effect profiles on non-compliance. The authors took steps to avoid attrition between the two rounds and, at the end of the study, all 25 experts had participated. To minimise biases, all materials given to the experts were standardised and the experts were blinded to the identities of the four antipsychotic treatments. To bring experts closer to consensus, feedback comprised both the individual and group responses. Sampling variation and intra-individual uncertainty were taken into account by bootstrapping. Despite these strengths, the authors noted that the Delphi experts were not randomly selected, thus raising the possibility of being a biased sample of experts on the treatment of schizophrenia. However, the authors also pointed out, that there was no a priori reason to assume that any bias would be related to the views of the experts on the relationship between drug side effects and compliance. XBC: Survival analysis methods were used to summarise the data and estimate non-compliance rates after 3, 6 and 12 months' treatment with conventional antipsychotics. XBD: Not reported. XBM: Only those studies reporting a time-specific non-compliance rate were judged to be relevant. XBP: A total of 32 publications were included in the analysis. XBV: Not stated. XCE: A two-round Delphi study involving 25 leading European and North American experts on schizophrenia was undertaken. These experts were asked to assess the impact of different side effect profiles on non-compliance. Information on side-effect profiles for conventional and atypical antipsychotics, as derived from published studies and the Cochrane Collaboration Reviews, was given to each expert. The experts were blinded to the identities of the atypical antipsychotics (identified by fictitious names) and were presented in a balanced order. The experts were then asked to estimate, using the information supplied, an estimate of the "lowest likely", "most likely" and "highest likely" non-compliance rates after 3, 6 and 12 months' treatment for each atypical antipsychotic. Four weeks later, each expert was presented with all his estimates and those of the other experts (anonymously). Each expert was then asked to confirm or revise their initial estimates in the light of other experts' conclusions. This was done in order to bring the experts closer to a consensus. XRR: The estimated differential 1-year relapse rate of olanzapine compared to quetiapine was 6.1% (95% confidence interval, CI: 3.2 - 9.3; 99% CI: 2.3 - 11.1). This difference was highly significant as the 99% CI did not include zero.The estimated differential 1-year relapse rate of risperidone compared to quetiapine was 5.6% (95% CI: 2.7 - 9.3; 99% CI: 1.5 - 11.4). Again, this difference was highly significant.The estimated differential 1-year relapse rates of ziprasidone compared to quetiapine were small and statistically insignificant. XCO: The indirect costs were not included in the analysis. XCU: US dollars ($) when the US data sets were used. UK pounds sterling () when the UK data sets were used. XSA: The costs were treated in a stochastic manner. The authors reported the mean incremental costs with their respective 95% and 99% CIs. XSY: No sensitivity analyses were performed. XEB: See the 'Effectiveness Results' section. XCR: The modelled estimates of difference of olanzapine from quetiapine in incremental 1-year per patient costs of differing side effect profiles were $530 (95% CI: 275 - 800; 99% CI: 200 - 960) for US costs and 630 (95% CI: 330 - 960; 99% CI: 235 - 1,140) for UK costs.The modelled estimates of difference of risperidone from quetiapine in incremental 1-year per patient costs of differing side effect profiles were $485 (95% CI: 235 - 800; 99% CI: 130 - 985) for US costs and 575 (95% CI: 280 - 960; 99% CI: 155 - 1,170) for UK costs.The modelled estimates of difference of ziprasidone from quetiapine in incremental 1-year per patient costs of differing side effect profiles were $45 (95% CI: -145 - 235; 99% CI: -240 - 320) for US costs and 50 (95% CI: -175 - 275; 99% CI: -285 - 370) for UK costs. These differences were not statistically significant since both sets of CIs contained 0. XCB: The costs and benefits were not combined since a cost-consequences approach was taken. XAU: Differing side effect profiles of the newer antipsychotic agents were likely to lead to different compliance rates and, consequently, variation in the relapse rates. The authors also concluded that the cost implications of the heterogeneous clinical outcomes were considerable. CO1: United Kingdom XIM: The authors seem to suggest that the results should be confirmed in patient-based studies. If these confirm the authors' results it would imply that, for 1.5% of UK patients with schizophrenia, changing the medication to an atypical antipsychotic with a better side effect profile could realise savings of up to 1 million per annum in direct treatment costs. KWO: Antipsychotic Agents /economics /therapeutic use; Benzodiazepines /economics /therapeutic use; Dibenzothiazepines /economics /therapeutic use; Great Britain; Health Care Costs; Humans; Patient Compliance; Piperazines /economics /therapeutic use; Quetiapine Fumarate; Recurrence; Risperidone /economics /therapeutic use; Schizophrenia /drug therapy /economics; Thiazoles /economics /therapeutic use XAC: 22003000956 XID: 30 Apr 2004 XLA: English XPR: 12870371 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22003000956 Record #18 %%%% TTL: An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics AUT: Tilden D, Aristides M, Meddis D, Burns T XSO: Clinical Therapeutics XYR: 2002 VOL: 24(10) PAG: 1648-1667 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The use of quetiapine versus haloperidol for the treatment of patients with schizophrenia who were only partially responsive to conventional antipsychotics. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients who met the following criteria:schizophrenia according to the DSM-IV diagnostic criteria;age less than or equal to 18 years;a history of persistent positive symptoms while taking therapeutic doses of an antipsychotic agent and a score of at least 15 on the Positive and Negative Syndrome Scale (PANSS), with a score of at least 4 (moderately ill) on one or more of the items of delusion, conceptual disorganisation, hallucinatory behaviour, or suspicion/persecution; anda score of at least 3 on the Clinical Global Impression Severity of Illness scale.These patients received 4 weeks of treatment with fluphenazine (20 mg/dL). Those who showed a partial response or no response to fluphenazine (defined as an improvement in the PANSS total score of less than 30% from baseline to week 4 and a PANSS total score at week 4 of at least 15) participated in a randomised clinical trial (RCT) that constituted the basis for this modelling study. XSG: The setting was secondary care. The economic study was carried out in the UK. XDD: The effectiveness data were mainly taken from a study published in 2000. The remaining effectiveness data required for the construction of the model were extracted from literature published between 1974 and 1995. The resource use data were derived from the main source-study (2000) and one additional paper published in 1998. Prices relating to 1998 to 2000 were used. XDR: The direct costs included in the economic analysis were consistent with the perspective of the study (the UK NHS). The costs were for medication (quetiapine or haloperidol) and the medical services required at each health state of the model. The quantities were not reported separately from the unit costs. However, in most cases, the resources required were individually estimated for each state, and then a unit cost was attached. The final total costs were derived using modelling techniques. The resources needed were estimated using actual data from the main source-study (for medication costs), and treatment protocols described in another study. The drug prices were derived from the British National Formulary (1999). The unit costs for the medical services were taken from "Unit costs of health and social care, 2000" and the Chartered Institute of Public Finance and Accountancy (2000). The costs of three health states were directly derived from a study published in 1998. The costs were discounted at a rate of 6%, which was appropriate as they were incurred during a 5-year period. The price year was not explicitly stated. XMB: The benefit measures used in the economic analysis were the number of relapses avoided, and the time spent (per patient) in a response state due to treatment. XOA: The outcomes assessed in the review included:the response and EPS rates in patients, partially responsive to fluphenazine, who were receiving quetiapine or haloperidol for 8 weeks;the transition probabilities of patients with or without EPS to noncompliance;the transition probabilities of compliant, noncompliant, or nonresponding patients to relapse; andthe transition probabilities of patients with relapse to suicide. XSS: Not stated. XSS: The effectiveness data were derived from a review of completed studies. The authors made some key assumptions, some of which were supported by expert opinion. CED: The main study used for the construction of the Markov model was a multi-centre, randomised, double-blind prospective trial (the PRIZE study). This study was selected as the basis of the model because the study population comprised partial responders, a common treatment group in schizophrenia, but a group for whom specific studies were scarce. Further details of the study are provided elsewhere (see Other Publications of Related Interest). The inclusion criteria for the remaining studies in the review were not stated. EST: A Markov model was constructed to extrapolate the effectiveness and cost results of an 8-week RCT over a 5-year period. The model included 11 health states and had a cycle time of 3 months. The first five health states were adopted from end points in the RCT. They involved states of PANSS (full, partial, or no improvement) following treatment with quetiapine or haloperidol, combined with the presence or absence of extrapyramidal symptoms (EPS). The remaining six states included states of relapses (fully, partially, or not responsive to treatment) plus a state of suicide. OI: The authors made appropriate comparisons of their results with the findings of other studies, and found them to be consistent. However, the issue of generalisability to other settings was not explicitly addressed. The results were adequately reported and reflected the scope of the study, which involved only patients with schizophrenia who were partially responsive to conventional antipsychotics. The authors were aware that their findings might not be relevant to patients with other forms of schizophrenia.One limitation of the study was the assumption that the response rates observed in the 8-week RCT were maintained over the 5-year duration of the Markov model, as long as patients remained compliant with the treatment. However, the authors justified this key assumption by stating that no long-term data were available for quetiapine in partially responsive patients, and that this assumption was consistent with data from patients with acute schizophrenia. Another limitation reported was that the model included only one side effect of treatment. The authors felt that the analysis might have missed some benefits of quetiapine treatment, such as a reduction in the frequency of other side effects. SCO: Quetiapine was studied as it had been proven, in an RCT, to be effective in patients with partially responding schizophrenia. The choice of the comparator (haloperidol) was not justified. However, it is a drug indicated for the treatment of schizophrenia. You should decide whether this comparator represents current practice in your setting. VB: The estimation of benefits was based on a Markov model. This was appropriate for this purpose since it included all possible health outcomes resulting from the treatment of partially responding schizophrenia. In addition, its duration allowed the long-term effectiveness of therapy to be evaluated. VC: All the categories of costs relevant to the perspective adopted (NHS) were included in the analysis. The costs and the quantities were not reported separately, which may limit the replication of the study results in other settings. A sensitivity analysis of some cost components was conducted. However, this was not extensive and, as such, only partially addressed the uncertainty surrounding the estimates. Discounting was carried out as appropriate. The unit costs were derived from sources published within a 3-year period. It was not stated whether the prices were all uplifted to the same year. The use of a single price year would aid future reflation exercises. VM: No systematic review was undertaken for the estimation of effectiveness. Most of the data were taken from an RCT, which is the optimal study design for the evaluation of effectiveness. The rest of the effectiveness estimates were derived from other studies, possibly selectively. The number of primary studies used, besides the main source-study, was very limited. Thus, the authors did not report any consideration of the validity or the impact of differences between the primary studies when estimating the effectiveness. In terms of the key assumptions made, the authors did not always justify their choices, although in one case there was expert agreement. Most of the assumptions were subjected to a sensitivity analysis. The internal validity of the RCT is likely to have been high. However, given the ad hoc use of other sources, it was not possible to judge the validity of all model inputs. XBC: The results of the primary studies may have been used selectively. No method of combination was stated. XBD: Not stated. XBM: Not stated. XBP: The effectiveness evidence was derived from 3 primary studies and one review. XBV: Not stated. XCE: The authors' assumptions about one estimate of effectiveness were supported by a panel of experts from the UK, experienced in treating patients with the same characteristics as those of the target population used in the model. The authors also made other key assumptions in the construction of the model. XCF: The relapse rate for nonresponding patients was assumed to be the same as that for noncompliant patients (0.209). In addition, the same relapse rates were assumed for both quetiapine- and haloperidol-treated patients. However, in clinical practice, although the probability of relapse for nonresponding patients is the same, the responsiveness to treatment differs depending on the drug administered. Another key assumption was that the response rates observed in the 8-week RCT were maintained for the 5-year duration of the Markov model, as long as the patients remained compliant with the treatment. This might not be the case in a clinical setting. XDI: Mental disorders. XFU: None stated. XOP: Emsley RA, Raniwalla J, Bailey PJ, Jones AM, for the PRIZE Study Group. A comparison of the effects of quetiapine ('Seroquel') and haloperidol in schizophrenic patients with a history and a demonstrated, partial response to conventional antipsychotic treatment. International Clinical Psychopharmacology 2000;15:121-31. XRR: The response and EPS rates for partially responsive patients receiving quetiapine for 8 weeks were:for PANSS improvement of +/- 30% and no EPS, 22%;for PANSS improvement of +/- 30% and EPS, 6%;for PANSS improvement of +/- 20% but less than 30% and no EPS, 8%;for PANSS improvement of +/- 20% but less than 30% and EPS, 7%; andfor PANSS improvement of less than 20% (independent of EPS status), 56%.The response and EPS rates of partially responsive patients receiving haloperidol for 8 weeks were:for PANSS improvement of +/- 30% and no EPS, 8%;for PANSS improvement of +/- 30% and EPS, 9%;for PANSS improvement of +/- 20% but less than 30% and no EPS, 9%;for PANSS improvement of +/- 20% but less than 30% and EPS, 8%;for PANSS improvement of less than 20% (independent of EPS status), 67%.The transition probabilities were:for patients with EPS to noncompliance, 0.180;for patients without EPS to noncompliance, 0.013;for recently stabilised and compliant patients to relapse, 0.051;for noncompliant or nonresponding patients to relapse, 0.209; andfor suicide following relapse, 0.002. XCO: The indirect costs were not included in the analysis. This was consistent with the perspective adopted. XCU: UK pounds sterling (). XSA: The costs were treated deterministically. No statistical tests were carried out when analysing the costs. XSY: One-way sensitivity analyses were conducted to test the robustness of the results. The parameters of uncertainty examined were divided into four categories:variables related to the model structure (discount rate, duration of the model);variables related to the RCT data (difference in the proportion of patients in each response/EPS state between the two groups);variables concerning the probability of relapse in the various categories of patients (e.g. nonresponding, noncompliant); andvariables related to the health state treatment costs (nonresponse and relapse costs).No justification was given for the ranges selected. They appear to have been based on a decrease or increase in each base-case value by a specific percentage. XEB: The average number of relapses expected (discount rate 1.5%) over the 5 years was 2.30 per quetiapine-treated patient (2.38 undiscounted) and 2.49 per haloperidol-treated patient (2.58 undiscounted). This meant that a quetiapine-treated patient would experience an average of 0.19 fewer relapses than a haloperidol-treated patient.Only the incremental value was presented for the time spent in a response state. This was 0.34 additional years (0.35 undiscounted) in response health state per quetiapine-treated patient, compared with a haloperidol-treated patient, for a period of 5 years.The model accounted for only one side effect, EPS. XCR: The costs were discounted at a rate of 6%.The total costs per patient over 5 years were 38,106 for quetiapine and 38,350 for haloperidol.The total incremental cost of quetiapine was -244 per patient treated (-316 undiscounted). This meant that treatment with quetiapine was less costly than with haloperidol.The cost of the one side effect (EPS) considered in the study was included in every health state cost. XCB: The estimated costs and benefits were not combined into a single ratio, as treatment with quetiapine dominated treatment with haloperidol. Quetiapine was associated with a slight reduction in costs compared with haloperidol, and an improvement in outcomes (lower number of relapses and longer period spent in a response state). The results were, in general, robust to sensitivity analyses. Quetiapine was shown to be more effective than haloperidol under any scenario examined. It also remained cost-saving or cost-neutral under most scenarios. The only parameters that reversed this result (led to quetiapine being more costly) were reductions in the following:the difference in the proportion of patients in each response/EPS state between the two groups;the probability of relapse in nonresponding or noncompliant patients;the cost of relapse; andthe cost of the nonresponse state. XAU: Quetiapine was more effective and less costly than haloperidol for the treatment of patients with schizophrenia who were partially responsive to conventional antipsychotics. CO1: United Kingdom XIM: The authors suggested that quetiapine could significantly improve the treatment of patients with schizophrenia who are partially responsive to conventional antipsychotics, and who are often difficult to treat adequately, without increasing the economic burden on the health service. KWO: Adult; Antipsychotic Agents /adverse effects /economics /therapeutic use; Costs and Cost Analysis; Dibenzothiazepines /adverse effects /economics /therapeutic use; Haloperidol /adverse effects /economics /therapeutic use; Humans; Markov Chains; Models, Economic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia /drug therapy; Treatment Outcome XAC: 22003007664 XID: 31 Jul 2004 XLA: English XPR: 12462294 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22003007664 Record #19 %%%% DOI: 10.1111/j.1440-1614.2005.01509.x TTL: Assessing cost-effectiveness of drug interventions for schizophrenia AUT: Magnus A, Carr V, Mihalopoulos C, Carter R, Vos T XSO: Australian and New Zealand Journal of Psychiatry XYR: 2005 VOL: 39(1-2) PAG: 44-54 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: New neuroleptics for the treatment of patients with schizophrenia were examined. These were clozapine (CLO; 400 mg/day), risperidone (RIS; 5 mg/day) and olanzapine (OLA; 15 mg/day). Eight treatment strategies were considered:RIS versus typical neuroleptics,RIS versus typical neuroleptics with side effects,RIS versus low-dose typical neuroleptics,OLA versus typical neuroleptics,OLA versus typical neuroleptics with side effects,OLA versus RIS,CLO versus typical neuroleptics for patients with a chronic course of disorder with little deterioration, andCLO versus typical neuroleptics for patients with a chronic course of disorder with clear deterioration. XTI: Treatment. XEC: Cost-utility analysis. XPA: The study population comprised patients with schizophrenia. This included paranoid, hebephrenic, catatonic, undifferentiated, schizoaffective, delusional disorder and other non-organic non-affective psychotic disorders. XSG: The setting was secondary care. The economic study was carried out in Australia. XDD: The effectiveness data came from studies published between 1980 and 2004. Some resource use data came from studies published in 1998 and 2003. The price year was 2000. XDR: The cost analysis was performed from the perspective of the health sector. However, the costs to the patient associated with medication were also reported. The health services included in the economic evaluation were the marginal cost of changing from one medication regimen to another. Thus, with the exception of blood testing associated with CLO, only drug costs were considered. Physician visits were assumed to be constant and were not included. The authors stated that cost-offsets due to a fall in resource use associated with more effective drugs were not taken into consideration because of a lack of data. The unit costs and some information on resource use were provided. Resource use was estimated on the basis of published data and recommended daily doses. The costs came from official Australian sources, such as the Department of Health and the Pharmaceutical Benefit Scheme. Given the long time horizon, a discount rate of 3% was applied. The price year was 2000. XMB: The summary benefit measure used was the number of disability-adjusted life-years (DALYs) associated with each treatment strategy. DALYs were estimated using the modelling approach and combining years of life lost to premature mortality and years lived with disability. Given the long time horizon, a discount rate of 3% was applied. XOA: The outcomes assessed from the literature were:the length of illness in patients with schizophrenia;the number of Australians in the year 2000 affected by schizophrenia;the annual remission rate;the disease prevalence (male and female);the baseline adherence level for people taking typical neuroleptics;the percentage of typical and atypical neuroleptics with moderate or severe side effects;the percentage of persons on typical neuroleptics taking a low dose;the relative risk of all-cause mortality for individuals older than 15 years of age;the disability weights (DW) associated with specific health states;the impact of weight gain on ischaemic heart disease, ischaemic stroke, diabetes mellitus and colorectal cancer;the reduction in suicide risk;the effect size for each strategy compared; andimprovements in DW due to symptom reduction and side effect profile.The health benefits associated with CLO, RIS and OLA were also obtained from the literature, but only data for RIS compared with typical neuroleptics were reported. XSS: Not stated. XSS: The effectiveness evidence was derived from a synthesis of completed studies. CED: Published evidence was used to derive clinical estimates. It was unclear whether a systematic review of the literature was undertaken to identify the primary studies. The authors stated that systematic reviews and recent randomised trials were searched for clinical evidence. The mortality risk for schizophrenia was derived from Australian Bureau of Statistics, while the relative risk of all-cause mortality came from a meta-analysis. The DWs came from a study that used a questionnaire based on six selected items from the World Health Organization Disability Assessment Schedule, the Lancaster Lancashire Quality of Life Profile and the Social Contact Questionnaire, plus two questions capturing the respondents' self-rating of satisfaction with independence and with life in general. The statistical approaches used to calculate the effect size were reported. EST: A Markov model was constructed to model prevalent cases of schizophrenia and related conditions in Australia in the year 2000, through annual cycles with relevant hazards and marginal costs until the whole cohort had died or reached 100 years of age. No further details of the decision model were reported. OI: The authors reported extensively findings of other economic evaluations, but noted some drawbacks of published studies. The issue of the generalisability of the study results to other settings was not addressed, but CIs for cost, benefits and cost-utility ratios were calculated to address the issue of uncertainty in the final estimates. The authors discussed the problems of feasibility, in particular acceptability of the interventions to stakeholders. The limitations of the clinical trials carried out among patients with schizophrenia were pointed out. These included, for example, the high drop-out rate, the short time horizon, the inclusion of patients with established schizophrenia and the exclusion of patients with a history of drug abuse. SCO: The rationale for the selection of the comparators was clear. In addition, the choice of the interventions was appropriate for the study question. Newer drugs were compared with medications commonly used to treat schizophrenia. You should decide whether they are valid comparators in your own setting. VB: A justification for the use of DALYs was provided. In general, scarce information on quality of life was available in the literature. DALYs also have the advantage of being fairly comparable with the benefits of other health care interventions. However, it was stated that the current treatments had a substantial impact on quality of life rather than on life extension. Thus, caution is required when making comparisons with the benefits of other strategies. Further, the authors noted that the DWs were based on clinician-rated values rather than on patient-rated ones. VM: The effectiveness evidence came from the literature. However, the methods and conduct of the review were not reported. No information on the search and inclusion or exclusion criteria was provided. The number of studies included in the review was reported but, with the exception of a few clinical trials, the primary studies were not described. Thus, it was not possible to assess the validity of the primary studies. The methods used to calculate some clinical inputs were reported. The authors noted that some data estimated from clinical trials did not consider specific side effects that would have been relevant to the current analysis. The clinical outcomes were varied appropriately in a probabilistic sensitivity analysis. XBC: Statistical methods were used to combine some primary estimates. In particular, the average effect size within studies was calculated, and then pooled across studies using the random-effects method. XBD: Not stated. XBM: Not stated. XBP: Twenty-nine primary studies appear to have been used to provide clinical data. Other studies were probably used to derive the health benefits associated with the drugs under investigation, but were not reported. XBV: Not stated. XDI: Mental disorders. XFU: None stated. XOP: Almond S, O'Donnell O. Cost analysis of the treatment of schizophrenia in the UK. A simulation model comparing olanzapine, risperidone and haloperidol. Pharmacoeconomics 2000;17:383-9.Palmer CS, Revicki DA, Genduso LA, et al. A cost-effectiveness clinical decision analysis model for schizophrenia. American Journal of Managed Care 1998;4:345-55.Mauskopf JA, Muroff M, Gibson PJ, Grainger DL. Estimating the costs and benefits of new drug therapies: atypical antipsychotic drugs for schizophrenia. Schizophrenia Bulletin 2002;28:619-35.Zhao Z. A retrospective evaluation of olanzapine risperidone in the treatment of schizophrenia. Managed Care Interface 2002;15:75-81. VC: The authors stated that the cost analysis was carried out from the perspective of the health care sector. Only the drug costs (and blood tests, whenever relevant) were included in the analysis. However, it was unclear which types of patient costs were considered since they were broken down into those relevant to the government and those relevant to the patients. The unit costs were reported. The resource use data reflected treatment patterns in the authors' setting. The price year was reported, which aids reflation exercises in other settings. The costs were specific to the study setting but probabilistic distributions were assigned in the Monte Carlo simulation. XRR: The average length of illness in patients with schizophrenia was 15 years (range: 0 - 54). Disease prevalence was 0.23% (range: 0.16 - 0.31) among men and 0.15% (range: 0.1 - 0.19) among women. Thus, there were 37 000 Australians in the year 2000 affected by schizophrenia.The annual remission rate was 1.5% (range: 1 - 2).The baseline adherence level for people taking typical neuroleptics was 54%.The relative risk of all-cause mortality for individuals older than 15 years of age was 1.56.The DWs ranged from 0.21 for the mildest health state to 0.96 for the worst health state.For the impact of weight gain on ischaemic heart disease, ischaemic stroke, diabetes mellitus and colorectal cancer, the mean relative risks was 1.03 (range: 1.01 - 1.05) for colon cancer, 1.04 (range: 1.02 - 1.06) for ischaemic heart disease and stroke, and 1.11 (range: 1.07 - 1.14) for diabetes.Moderate side effects were observed for 15% of persons on typical neuroleptics and 9% of those on atypical neuroleptics. Severe side effects were found in 10% (typicals) and 6% (atypicals), respectively. Seventy per cent of persons on typical neuroleptics were taking a low dose.The reduction in suicide risk was 50% for patients on CLO and 0 for patients on other drugs.The effect size was:0.219 for RIS versus typical neuroleptics;0.219 for RIS versus typical neuroleptics with side effects;0.126 for RIS versus low-dose typical neuroleptics;0.251 for OLA versus typical neuroleptics with or without side effects;0.096 for OLA versus RIS;0.416 for CLO versus typical neuroleptics with little deterioration; and0.63 for CLO versus typical neuroleptics with clear deterioration.The improvements in DW due to symptom reduction and side effect profile (and the combined improvement) were, respectively:0.033 and 0.010 (0.043, 95% confidence interval, CI: 0.018 - 0.079) for RIS versus typical neuroleptics;0.031 and 0.073 (0.105, 95% CI: 0.077 - 0.142) for RIS versus typical neuroleptics with side effects;0.019 and 0.008 (0.027, 95% CI: -0.001 - 0.060) for RIS versus low-dose typical neuroleptics;0.038 and 0.010 (0.046, 95% CI: 0.027 - 0.078) for OLA versus typical neuroleptics;0.038 and 0.073 (0.109, 95% CI: 0.086 - 0.143) for OLA versus typical neuroleptics with side effects;0.015 and 0.0 (0.015, 95% CI: -0.014 - 0.046) for OLA versus RIS;0.064 and 0.007 (0.071, 95% CI: 0.042 - 0.131) for CLO versus typical neuroleptics with little deterioration; and0.104 and 0.010 (0.109, 95% CI: 0.065 - 0.188) for CLO versus typical neuroleptics clear deterioration. XCO: The indirect costs were not considered in the economic evaluation. XCU: Australian dollars (Aus$). XSA: The costs were treated deterministically. XSY: A Monte Carlo simulation was used to represent uncertainty ranges of costs, benefits and cost-utility ratios. Probability distributions of the parameters were derived from published data or experts' opinions and were reported. XEB: The incremental DALYs were:3,600 (95% CI: 1,500 - 7,300) with RIS versus typical neuroleptics (eligible population 9,300);3,000 (95% CI: 2,000 - 4,300) with RIS versus typical neuroleptics with side effects (eligible population 1,800);2,200 (95% CI: -150 - 5,300) with RIS versus low-dose typical neuroleptics (eligible population 9,300);4,300 (95% CI: 2,100 - 8,100) with OLA versus typical neuroleptics (eligible population 9,300);3,100 (95% CI: 2,100 - 4,400) with OLA versus typical neuroleptics with side effects (eligible population 1,800);340 (95% CI: -470 - 1,200) with OLA versus RIS (eligible population 3,300);11,000 (95% CI: 6,900 - 17,000) with CLO versus typical neuroleptics, chronic with little deterioration (eligible population 11,000); and9,900 (95% CI: 4,600 - 15,000) with CLO versus typical neuroleptics, chronic with clear deterioration (eligible population 5,400). XCR: The incremental costs (in Aus$millions) were:Aus$180 (95% CI: 130 - 240) with RIS versus typical neuroleptics (eligible population 9,300);Aus$60 (95% CI: 46 - 75) with RIS versus typical neuroleptics with side effects (eligible population 1,800);Aus$180 (95% CI: 130 - 240) with RIS versus low-dose typical neuroleptics (eligible population 9,300);Aus$390 (95% CI: 280 - 530) with OLA versus typical neuroleptics (eligible population 9,300);Aus$120 (95% CI: 87 - 140) with OLA versus typical neuroleptics with side effects (eligible population 1,800);Aus$53 (95% CI: 39 - 72) with OLA versus RIS (eligible population 3,300);Aus$470 (95% CI: 330 - 630) with CLO versus typical neuroleptics, chronic with little deterioration (eligible population 11,000); andAus$230 (95% CI: 160 - 310) with CLO versus typical neuroleptics, chronic with clear deterioration (eligible population: 5,400). XCB: Incremental cost-utility ratios were calculated to combine the costs and benefits of the alternative treatment strategies examined in the study.The incremental cost per DALY (in Aus$thousands) was:Aus$48 (95% CI: 27 - 110) with RIS versus typical neuroleptics (eligible population 9,300);Aus$20 (95% CI: 15 - 27) with RIS versus typical neuroleptics with side effects (eligible population 1,800);Aus$80 (95% CI: 36 - dominated) with RIS versus low-dose typical neuroleptics (eligible population 9,300);Aus$92 (95% CI: 53 - 170) with OLA versus typical neuroleptics (eligible population 9,300);Aus$38 (95% CI: 87 - 50) with OLA versus typical neuroleptics with side effects (eligible population 1,800);Aus$160 (95% CI: 44 - dominated) with OLA versus RIS (eligible population 3,300);Aus$42 (95% CI: 31 - 62) with CLO versus typical neuroleptics, chronic with little deterioration (eligible population 11,000);Aus$23 (95% CI: 17 - 47) with CLO versus typical neuroleptics, chronic with clear deterioration (eligible population 5,400).The authors also evaluated specific elements of the interventions that related to aspects of equity, strength of evidence, feasibility and acceptability. The analysis revealed the following results. First, there was sufficient evidence to make valid comparisons between drug interventions for established schizophrenia. Second, increased prescribing of CLO was feasible while maintaining strict monitoring of haematological side effects. Third, clinicians and patients place different value on side effects of neuroleptics and the importance given them in the analysis. Finally, the arbitrary use of an A$50,000 threshold was considered too low or inappropriate for schizophrenia. XAU: In general, the high costs of risperidone (RIS) and olanzapine (OLA) did not balance the modest clinical effects (expect in the case of those experiencing moderate to severe side effects on typical neuroleptics), while greater clinical improvements associated with clozapine (CLO) appear to justify its high cost. Using a threshold of Aus$50,000 per disability-adjusted life-year (DALY), low-dose typical neuroleptics were a cost-effective strategy for patients with established schizophrenia, while RIS should be reserved for those experiencing moderate to severe side effects on typical neuroleptics. OLA should only be prescribed when RIS is not clinically indicated. Earlier introduction of CLO might be cost-effective. CO1: Australia XIM: The study results suggested that low-dose neuroleptics should be used for the treatment of established schizophrenia, with RIS being restricted to patients experiencing moderate to severe side effects on typical neuroleptics. The authors noted that when the patent period expires, the cost of drugs should fall substantially, making OLA and RIS more cost-effective than the actual price levels. The authors recommended "outcome measurement in such studies include quality of life (both patient- and clinician-rated), social and economic functioning, drug tolerability, compliance, satisfaction and side effects". KWO: Antipsychotic Agents /adverse effects /economics /therapeutic use; Australia; Benzodiazepines /adverse effects /economics /therapeutic use; Clozapine /adverse effects /economics /therapeutic use; Cost-Benefit Analysis /statistics & numerical data; Disability Evaluation; Dose-Response Relationship, Drug; Drug Costs /statistics & numerical data; Humans; National Health Programs /economics; Quality-Adjusted Life Years; Risperidone /adverse effects /economics /therapeutic use; Schizophrenia /drug therapy /economics XAC: 22005000358 XID: 31 Jan 2006 XLA: English XPR: 15660705 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22005000358 Record #20 %%%% DOI: 10.1080/08880010590896468 TTL: A prospective randomized trial of the antiemetic efficacy and cost-effectiveness of intravenous and orally disintegrating tablet of ondansetron in children with cancer AUT: Corapcioglu F, Sarper N XSO: Pediatric Hematology and Oncology XYR: 2005 VOL: 22(2) PAG: 103-114 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study compared orally disintegrating tablets (ODT) and intravenous (IV) formulations of ondansetron in controlling nausea and vomiting in children receiving chemotherapy regimens without cisplatin. The oral formulation (ZOFRAN ZYDIS tablet; GlaxoSmithKline) was administered at a dose of either 4 mg (body surface area <= 0.8 m2) or 8 mg (body surface area > 0.8 m2). The IV formulation (ZOFRAN ampoule; GlaxoSmithKline) was administered at a dose of 5 mg/m2 every 12 hours. XTI: Prevention. XEC: Cost-effectiveness analysis. XPA: The study population comprised children and adolescents with cancer who were receiving chemotherapy. Patients with other underlying disorders causing emesis (e.g. gastrointestinal disease, brain tumours and brain metastases) and/or having courses containing cisplatin were excluded. XSG: The setting for the study was not explicitly stated. However, given the health technology involved it is likely to have been secondary care. The economic study was carried out in Izmit-Kocaeli, Turkey. XDD: The effectiveness data were gathered between October 2003 and March 2004. The resource use data appears to have been collected during the same period. The price year was not reported. XDR: The direct costs included were the cost of each tablet consumed by the patient in the oral group and the cost of every ampoule (even if the whole content was not used) for the IV group. No other costs were included. It would appear that data on resource quantities were obtained from the single study used for the effectiveness analysis, while the cost data might have been collected from the authors' own setting. The date to which the costs related was not reported. Discounting was not performed but, given the short timeframe involved (less than one month), this seems appropriate. The costs estimated were the average costs. XMB: The measure of benefit used was the number of courses and days with complete antiemetic control (no nausea or vomiting). This was obtained directly from the effectiveness analysis. XSD: The study was a randomised controlled trial (RCT) that was carried out in a single institution. The patients were consecutively randomised to either the ODT or IV formulation arm of ondansetron, during their admission to the unit to receive chemotherapy. Only the supervisor nurse was aware of the randomisation. At the end of each chemotherapy day, a paediatric oncologist who was unaware of the randomisation recorded the drug efficiency, along with adverse events and changes in the daily activity and appetite. The duration of follow-up was not explicitly stated, although it was likely that the patients were followed up for the duration of their chemotherapy. No loss to follow-up was reported. XSS: The effectiveness data were derived from a single study. OI: The authors made appropriate comparisons of their findings with those from other studies. There was a short discussion about other studies that had investigated the cost or effectiveness of oral and IV ondansetron and seemed to have reported similar conclusions to those in the present study. The authors discussed the variations in response rates found in various studies. They noted that their response rates were higher and put forward a number of possible explanations. For example, the exclusion of cisplatin-containing regimens, the mild to moderate emetogenicity of some courses, or a lack of emesis in young children.The issue of generalisability to other settings was not addressed. The cost estimates and efficacy data appear to have been derived from Turkish estimates and evidence, which may limit the generalisability of the study beyond Turkey. This is especially true given the lack of any sensitivity analysis. The authors did not present their results selectively. The study considered young patients undertaking all grades of chemotherapy and this was reflected in the authors' conclusions. SCO: Although no explicit justification was given for the comparator used, IV ondansetron would appear to represent current practice in the authors' setting. You should decide if it is a widely used health technology in your own area. VB: The estimation of benefits was obtained directly from the effectiveness analysis. This limits the comparability of the study results to those studies evaluating similar interventions and considering similar measures of health benefit. VC: The authors did not report the perspective adopted for their study, thus it is impossible to tell whether all the relevant costs were included. Only the specific costs of the drugs were included in the analysis. The authors acknowledged that the exclusion of the cost of inpatient stay, IV preparation consumables and nursing time is likely to lead to an underestimation of the true cost of the IV formulation. Therefore, their inclusion in the cost estimation would not change the conclusions of the study. VM: The analysis was based on an RCT, which was appropriate for the study question. It was unclear from the paper if the study sample was representative of the study population. In addition, there were no details on why or how the study sample was chosen from the study population. The randomisation method used to allocate the patients to the different arms was not reported, and there were no details of how participants differed from non-participants. The patient groups were shown to be comparable at analysis. The study population comprised 22 patients and 95 chemotherapy courses. Given that no details were provided about the sample size necessary to detect a significant difference between the two groups, it was unclear whether the non significant differences in effectiveness between the two groups were due to insufficient sample size or to a real equivalence between the two technologies. Some of the chemotherapy courses involved the same participants, but it was unclear whether the authors accounted for this non-independence of courses during the analysis. XAE: It was not stated whether the analysis of the clinical study was conducted on an intention to treat basis or for treatment completers only. However, assuming that there was no loss to follow-up, the two methods would provide the same results. The primary health outcome was the control of nausea and vomiting. The outcome was divided into four categories:complete control (no vomiting or nausea);major control (1 to 2 vomits or nausea);minor response (3 to 5 vomits and/or less than 5 hours of nausea);complete failure (more than 5 vomits and/or at least 5 hours of nausea, and generally indicating the administration of another antiemetic therapy).A paediatric oncologist assessed the outcomes through interviews with patients, parents and the observing nurse. Notes on the diary cards, as recorded by the parents and the observing nurse, were also evaluated. Changes in daily activities and appetite were also noted as a health outcome. The patients in the two groups were reported to be similar in age, gender, body surface area and emetogenic grade of their chemotherapy courses. XCL: The ODT and IV formulations were equally effective in controlling acute emesis of children. The control of emesis was greater for children receiving courses containing corticosteroids and for children younger than 10 years old. XDI: Neoplasms; Digestive system diseases; Pathological conditions, signs and symptoms. XFU: None stated. XLI: The costing was undertaken on the same patient sample as that used in the effectiveness study. It was not explicitly stated whether the costing was performed prospectively or retrospectively. XOP: Anastasia PJ. Effectiveness of oral 5-HT3 receptor antagonists for emetogenic chemotherapy. Oncology Nursing Forum 2000;27:483-93.Cohen IJ, Zehavi N, Buchwald I, et al. Oral ondansetron: an effective ambulatory complement to intravenous ondansetron in the control of chemotherapy-induced nausea and vomiting in children. Pediatric Hematology and Oncology 1995;12:67-72.Perez EA, Hesketh P, Sandbach J, et al. Comparison of a single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind randomised parallel study. Journal of Clinical Oncology 1998;16:754-60.White L, Daly SA, McKenna CJ, et al. A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimen given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic cemotherapy. Pediatric Hematology and Oncology 2000;17:445-55. XRE: The overall antiemetic response rates of the courses were 83% complete, 8% major, 4% minor and 5% failure. Complete response rates were not significantly different between boys and girls, (p=0.102).The two treatment groups did not differ in complete response rates (82% in the IV group versus 85% in the ODT group), (p=0.981), appetite (same as usual: 59% in the IV group and 72% in the ODT group), (p=0.141), and daily activities (same as usual: 55% in the IV group and 54 % in the ODT group), (p=0.525).The complete response rate was 94% in patients younger than 10 years and 69% in patients aged 10 years or older, (p=0.004). However, differences between IV versus ODT formulations in patients under 10 years and patients aged at least 10 years were not statistically significant.In 56 courses with Grade III and IV emetogenicity, the complete response rates were no different for IV (75%) or ODT formulations (80%), (p=0.931). There was also no difference in the appetite and daily activities between the two treatment arms, (p=0.272 and p=0.140, respectively).A total of 231 chemotherapy days were evaluated during the study. Daily response rates and appetites were no different between the two treatment arms, (p=0.728 and p=0.054, respectively). However, patients in the ODT arm showed less reduction in daily activities, (p=0.041).The complete response rates were higher for courses containing corticosteroids (39/41) than for courses without corticosteroids (40/54), (p=0.006). XSM: Patients were eligible if they met the inclusion criteria (see 'Study Population'), and were receiving their first course of chemotherapy, or had no nausea or vomiting during previous chemotherapy courses. Those receiving antiemetics during the preceding 24 hours were excluded. A total of 22 children and adolescents were enrolled in the study. No details on how the sample size was determined, the method of sample selection, or those who refused to participate, were provided. The number of patients allocated to each regimen was not reported. However, it was reported that there were 95 courses of chemotherapy, of which 56 were allocated to the IV arm and 36 to the ODT arm. XCO: No indirect costs were included. XCU: US dollars ($). The authors did not report the conversion rate used to convert Turkish liras (YTL) into US dollars. XSA: The authors reported that either the Kruskal-Wallis test or the Mann-Whitney test were used for continuous variables. However, they did not report whether the costs were regarded as a continuous variable. XSY: The authors do not appear to have performed any sensitivity analysis. XEB: See the 'Effectiveness Results' section. XCR: For the whole group, the mean cost of one course was $83.0 (+/- 65.9), which was $99.6 (+/- 74.5) in IV courses and $59.2 (+/- 41.6) in ODT courses, (p=0.004).In the whole group, the daily antiemetic cost was $34.8 (+/- 11.2). The daily costs were $43.6 (+/- 6.11) for the IV formulation and $23.9 (+/- 4.7) for the ODT formulation, (p<0.001). XCB: In the IV group, complete response was achieved in 46 courses (106 days) with a total antiemetic cost of $5,581.2. In the ODT group, complete response was achieved in 39 courses (87 days) with a total antiemetic cost of $2,464.8.The mean cost per successfully controlled course was $121.3 for the IV formulation and $63.2 for the ODT formulation. The costs per successfully controlled day were $52.6 (IV) and $28.3 (ODT), respectively. XAU: The orally disintegrating tablet (ODT) formulation of ondansetron was as effective as intravenous (IV) ondansetron. Therefore, ODT ondansetron was shown to be a safe, well-tolerated and cost-effective antiemetic for children receiving moderately and highly emetogenic chemotherapy without cisplatin. CO1: Turkey XIM: The authors acknowledged that the study may encourage paediatric oncologists to try ODT formulations in combination with dexamethasone in cisplatin-containing chemotherapy. KWO: Administration, Oral; Adolescent; Antiemetics /administration & dosage /economics; Antineoplastic Agents /adverse effects; Child; Child, Preschool; Cost-Benefit Analysis; Costs and Cost Analysis; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Neoplasms /complications /drug therapy; Ondansetron /administration & dosage /economics; Solubility; Treatment Outcome; Vomiting /prevention & control XAC: 22005000445 XID: 31 Jan 2006 XLA: English XPR: 15804995 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22005000445 Record #21 %%%% TTL: Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany AUT: Laux G, Heeg B M S, van Hout B A, Mehnert A XSO: PharmacoEconomics XYR: 2005 VOL: 23(Supplement 1) PAG: 49-61 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The three treatment strategies investigated were first-line treatment with haloperidol depot, long-acting risperidone and oral olanzapine for patients with schizophrenia. XTI: Treatment. XEC: Cost-effectiveness analysis and cost-utility analysis. XPA: The study population comprised patients with multiple schizophrenia relapses who experience total or partial recovery between episodes. In particular, it comprised patients aged 34.4 (standard deviation 11.0) years, with an average life expectancy, after correcting for suicide, of 61 years for men and 65 years for women. XSG: The study setting was secondary care. The economic study was carried out in Germany. XDD: The effectiveness and resource use data were derived from studies published between 1994 and 2003. The price year was 2004. XDR: The direct costs to the German health care system were included in the analysis. These were for drug costs, home treatment, psychiatrist visits, sheltered living, day care, hospitalisation and institutionalisation. Drug prices were obtained from the online version of the Rote List, and were checked for congruence with the German official price list. Other costs were derived from national references, tariffs and results from other studies. Since the costs were incurred over a 5-year period, all future costs were discounted at an annual rate of 5%, as recommended by German guidelines. The average costs were reported. The price year was 2004. XMB: The measure of benefits used was the quality-adjusted life-years (QALYs). These were derived by linking outcomes in terms of the PANSS with utility values according to the results of a study published in 1997. Other measures of benefits included the average number of relapses, the cumulative PANSS score (calculated as the sum of the annual average PANSS score over the 5 years) and time spent in psychosis. XOA: The outcomes assessed in the review were:the probabilities of side effects;the effectiveness of treatments in reducing the Positive and Negative Syndrome Scale (PANSS - a severity score used as the main indicator for the severity of a patient's condition);compliance rates with the medication;the disorganisation index, which measures the patient's ability to self care; andutility values. XSS: Not reported. XSS: The effectiveness data were derived from the literature and were supplemented by advice from a panel of five psychiatrists. CED: Not reported. EST: A discrete event simulation model was chosen to simulate individual patients and analyse relationships between events and expected costs and effects. In the model, treatment switches were made if relapse or side effects occurred, generating second- and third-line options within each strategy. XCF: The authors assumed an 11% reduction in the PANSS score for patients receiving conventional drugs, and 17% for those receiving atypical antipsychotic agents.Total recovery patients who were receiving treatment were estimated to have the following PANSS scores with atypical antipsychotic agent (conventional antipsychotic agent): 59 (63) for non severe, 84 (90) for medium severe and 99 (106) for very severe.For the first relapse after model entry for the partial recovery groups, the mean PANSS scores with atypical antipsychotic agent (conventional antipsychotic agent) were 115 (123) for non severe, 120 (128) for medium severe and 125 (134) for very severe.Between relapses, PANSS scores in these groups were estimated to decrease by 20 points for very severe, 30 for medium severe and 40 for non severe partial recovery.Between relapses, the PANSS score of total recovery patients was estimated to be 50.The authors assumed that compliance was higher with depot rather than oral medications, and that it would increase for all medications when administered in an environment that allowed closer supervision. For haloperidol, compliance was assumed to be 5% lower between relapses than during relapses. XDI: Mental disorders. XFU: Supported by Janssen Pharmaceutica N.V., Belgium and Janssen-Cilag GmbH, Germany. XOP: De Graeve D, Smet A, Mehnert A, Caleo S, Miadi-Fargier H, Mosqueda GJ, et al. Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis. Pharmacoeconomics 2005;23 Suppl 1:35-47.Chue PS, Heeg B, Buskens E, van Hout BA. Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada. Pharmacoeconomics 2005;23 Suppl 1:62-74.Heeg BM, van Aalst G, van den Arend JJ. A discrete events model of long-term outcomes and cost of treatment with long acting risperidone in schizophrenia. Value Health 2003;6:515-6. OI: The authors reported that their results agreed with those of similar models undertaken in other health care systems such as Belgium, the Netherlands, Canada and Italy. The issue of generalisability to other settings was addressed in the sensitivity analysis. The authors do not appear to have presented their results selectively, although it would have been desirable for them to have presented the results of their review and the methods employed in a more explicit manner. The authors reported a number of further limitations to their model. These were the way in which compliance was defined, restrictions on when medication switching was allowed, and the exclusion of indirect costs. SCO: A justification was given for using haloperidol and olanzapine as the comparators. They represented a mainstay treatment for schizophrenia and were still an acceptable treatment strategy. You should decide if these two interventions represent current practice in your own setting. VB: The estimates of measures of benefits were derived from the discrete event simulation model employed by the authors. This appears to have been appropriate for the study question. All benefits were appropriately discounted, with the authors reporting mean average results both discounted and undiscounted. VC: All the categories of cost relevant to the health care system perspective adopted appear to have been included in the analysis. No major relevant costs appear to have been omitted from the analysis. The costs and the quantities were not reported separately, which will limit the generalisability of the results. However, the authors did report the total costs by resource use category, which will help to minimise this limitation. The costs were derived from published sources and expert opinion. Appropriate sensitivity analyses were conducted. Since the costs were incurred during a 5-year period, all future costs were appropriately discounted. The price year was reported, which will assist any future inflation exercises. VM: The authors did not report if a systematic review of the literature was undertaken to identify all relevant research and minimise biases. Further, they did not provide any details of the methods used in the review, and provided very limited results arising from the review. However, the authors did explain in more detail how the effectiveness estimates were derived from experts. Given these limitations, it is not possible to ascertain that the best available evidence has been used to populate the model. XBC: Not reported. XBD: Not reported. XBM: Not reported. XBP: Approximately 10 studies were included in the review. XBV: Not reported. XCE: The effectiveness data derived from the literature were also supplemented by advice from a panel of five psychiatrists. Each expert was interviewed individually, guided by a questionnaire, and asked to evaluate the presented treatment alternatives, model structure, underlying assumptions and all estimates concerning transition probabilities. XRR: The authors reported very limited details of the review. In addition, many of the estimates used in the model were based on the results of the review and expert opinion. XCO: In line with the perspective adopted, indirect costs were not included. XCU: Euros (EUR). XSA: The costs were reported as point estimates (i.e. the data were deterministic). XSY: A series of one-way sensitivity analyses was undertaken by varying the PANSS reduction achieved by atypical agents, the disorganisation index, the location costs, the symptom severity during relapse, the probability of switch caused by side effects, the effect of non-compliance, the time between relapse and the discount rate. The authors also undertook sensitivity analyses by treating oral risperidone as second-line treatment, and oral risperidone and oral olanzapine as second-line treatment. XEB: Over the 5-year period, the long-acting risperidone strategy was estimated to avoid a mean number of undiscounted (discounted) relapses per patient of 0.23 (0.22) in comparison with haloperidol depot and 0.33 (0.32) in comparison with oral olanzapine.Long-acting risperidone reduced the cumulative PANSS score (discounted) by 25 points (23) in comparison with haloperidol depot and by 33 points (31) in comparison with olanzapine.The cumulative time in psychotic episodes (discounted) was 1.94 (1.72) years with haloperidol depot, 1.80 (1.59) with long-acting risperidone and 2.01 (1.78) with oral olanzapine.The QALYs gained (discounted) were 1.95 (1.78) with haloperidol depot, 2.06 (1.87) with long-acting risperidone and 1.97 (1.79) with oral olanzapine. XCR: The direct undiscounted (discounted) medical costs per patient after 5 years were EUR 97,336 (88,892) for haloperidol depot, EUR 95,316 (87,284) for long-acting risperidone and EUR 101,414 (92,706) for oral olanzapine. XCB: The costs and benefits were not combined as long-acting risperidone was found to be both more effective and less costly than oral olanzapine and haloperidol depot (i.e. long-acting risperidone was dominant).The results of the sensitivity analysis confirmed that long-acting risperidone provided greater clinical effectiveness and lower costs under the vast majority of scenarios tested.The results of the sub-group analysis showed that, among patients at high risk of non-compliance, long-acting risperidone was dominant. Further, it remained the most effective strategy in all severity sub-group analyses. XAU: Long-acting risperidone, as a first-line strategy, was more effective than first-line haloperidol depot or first-line oral olanzapine strategies. It also reduced the costs. CO1: Germany XIM: The authors reported that their findings have clear relevance for long-term treatment in clinical practice and formulary decisions. KWO: Administration, Oral; Antipsychotic Agents /administration & dosage /economics /therapeutic use; Benzodiazepines /administration & dosage /economics /therapeutic use; Cost of Illness; Cost-Benefit Analysis; Delayed-Action Preparations /economics; Economics, Pharmaceutical; Germany; Haloperidol /administration & dosage /economics /therapeutic use; Humans; Models, Economic; Quality-Adjusted Life Years; Risperidone /administration & dosage /economics /therapeutic use; Schizophrenia /drug therapy /economics XAC: 22005008350 XID: 31 Jan 2007 XLA: English XPR: 16416761 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22005008350 Record #22 %%%% TTL: Cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting AUT: Pueyo F, Lopez Olaondo L, Sanchez Ledesma M, Ortega A, Carrascosa F XSO: British Journal of Anaesthesia XYR: 2003 VOL: 91(4) PAG: 589-592 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CO1: Spain KWO: Adolescent; Adult; Aged; Antiemetics /economics /therapeutic use; Cost-Benefit Analysis; Dexamethasone /economics /therapeutic use; Double-Blind Method; Droperidol /economics /therapeutic use; Drug Therapy, Combination; Female; Humans; Middle Aged; Ondansetron /economics /therapeutic use; Postoperative Nausea and Vomiting /economics /prevention & control; Prospective Studies; Reproducibility of Results; Treatment Outcome XAC: 22003001601 XID: 28 Jul 2006 XLA: English XPR: 14504165 XUR: http://infodoc.inserm.fr/euronheed/publication.nsf/$AllEtudes/4523b659f2ca7ab7c12570c20035a2e8?OpenDocument&Name=-languageGB-viewSearch DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22003001601 Record #23 %%%% DOI: 10.1111/j.1600-0447.2006.00788.x TTL: Treatment costs and clinical outcome for first episode schizophrenia patients: a 3-year follow-up of the Swedish 'Parachute Project' and two comparison groups AUT: Cullberg J, Mattsson M, Levander S, Holmqvist R, Tomsmark L, Elingfors C, Wieselgren I M XSO: Acta Psychiatrica Scandinavica XYR: 2006 VOL: 114(4) PAG: 274-281 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study examined the "Parachute Project", a "need-specific treatment" programme for the management of first episode schizophrenia syndrome. The programme was delivered by a first episode psychotic (FEP) patient team within 24 hours after the first contact with the psychiatric clinic (in the hospital or patient's home). The intervention attempted to involve the family, or those closest to the patient, in the future delivery of health care. According to the project, antipsychotic medication should not be considered as the first choice of treatment during the initial weeks of treatment, but benzodiazepines and similar medications could be offered to treat insomnia and anxiety. The intervention relied on special crisis or residential homes, such as small-scale, non-institutional and home-like milieu, with few staff members. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients with schizophrenia syndrome. The inclusion criteria were every non-organic FEP patient aged between 18 and 45 years, with no dominating substance abuse, and with a diagnosis on intake of schizophreniform disorder, schizophrenia or schizoaffective disorder. XSG: The setting was mainly outpatient. The economic study was carried out in Sweden. XDD: The patients were recruited between 1996 and 1997. Therefore, clinical and economic data were gathered from 1996/97 for 3 years (the length of follow-up). The price year was not explicitly reported. XDR: The authors did not explicitly state the perspective chosen for the analysis. The analysis included the costs of inpatient stay and salaries for the outpatient contacts. Costs associated with time spent for conferences, waiting time, travel time, documentation and other administrative costs were not included. The unit costs were not presented separately from the resource quantities used. Resource use was estimated using data derived from the three treatment groups. Resource consumption was evaluated retrospectively in the historical group and prospectively in the Parachute Project and prospective groups. The sources of the costs were not explicitly stated. The cost of a night spent in the special crisis/residential homes at the Parachute Project centres could not be established uniformly and was valued at the cost of an ordinary inpatient stay. The price year was not explicitly stated, but the cost of an inpatient stay was estimated in 1996. XMB: The health outcomes were left disaggregated and no summary benefit measure was used in the economic analysis. In effect, a cost-consequences analysis was carried out. XSD: This was both a prospective and retrospective cohort study that was carried out at several centres in Sweden. The groups were not studied concurrently. The length of follow-up relevant for the current economic evaluation was 3 years. Only patients with complete data were included. Blinding was clearly not performed. XSS: The effectiveness evidence was derived from a single study. OI: The authors stated that although few randomised studies had been published, most of the studies generated results similar to those observed in the current study. The issue of the generalisability of the study results to other settings was not addressed and sensitivity analyses were not carried out, which could limit the external validity of the analysis. The study referred to the sub-group of patients with schizophrenia and this was reflected in the authors' conclusions. SCO: The rationale for the choice of the comparators was clear. The authors provided a brief description of all the treatments. You should decide whether they are valid comparators in your own setting. VB: No summary benefit measure was used in the analysis because a cost-consequences analysis was conducted. Please refer to the comments in the 'Validity of estimate of measure of effectiveness' field (above). VC: The perspective of the analysis was unclear. A detailed breakdown of the cost items was not provided, and only the costs of overnight stay and personnel for outpatient costs were included in the analysis. Limited information on the unit costs and resource quantities was provided, which will limit the possibility of replicating the analysis in other settings. The cost estimates were specific to the study setting and the impact of using alternative cost estimates was not investigated. Statistical tests were carried out, not only to assess the significance of the cost comparison but also to deal with the typical skewed distribution of costs due to the fact that a small number of patients consumed a large amount of resources. The price year was not reported, which will make reflation exercises in other time periods difficult. The authors made a conservative assumption in the estimation of accommodation costs in order to bias the results of the analysis in favour of conventional modalities of care. VM: The effectiveness data were estimated through a comparison of two prospective groups and a historical control group. Such a design was necessary because the different treatments were implemented in different time periods. Since the groups of patients were not evaluated concurrently, factors other than the study interventions might have affected the results of the analysis. In effect, time-dependent confounding variables such as variations in medical practice, evolution of subjects, or variability in the severity of illness could not be controlled because of the design of the study; this may represent an important limitation of the analysis. The study groups were balanced at baseline in terms of the demographics but some differences in the disease profile, which could have affected the robustness of the comparison, were observed. However, statistical analyses were not performed to take the impact of potential confounding factors arising from baseline differences into account.The authors noted that most of the clinical tools used to evaluate the effectiveness of the intervention were validated measures. The evidence came from several institutions, which enhances the representativeness of the patient sample considered in the study. Statistical analyses were carried out but, owing to the small sample size, it was unclear whether the study had sufficient power to detect statistically significant differences between the groups. The length of follow-up was appropriate, but the analysis of some clinical outcomes was restricted to those patients with complete follow-up data. These issues might limit the internal validity of the study. XAE: The analysis of the clinical study was restricted to those patients with complete follow-up data. The health outcomes used in the analysis were:functional status (assessed using the Global Assessment of Function, GAF);symptom severity (recorded with the Brief Psychiatric Rating Scale);working capacity;disability allowance;the rate of suicides; andsubjective satisfaction with care in patients and relatives (Parachute Project group only; assessed with two specially constructed 13-item 5-point scales).At baseline, the study groups were comparable in terms of their age, gender and civil status. However, there were no schizoaffective syndrome patients in the prospective group and more schizophrenia patients in the historical group than in the Parachute Project group. XCL: The effectiveness analysis showed that the Parachute Project was as effective as health care delivered by a high-quality social and biological psychiatry centre (prospective group), but significantly more effective than treatment-as-usual (historical group). XDI: Mental disorders; Health care: Patient care management. XFU: Supported by grants from the Swedish Board of Health and Welfare and the Research and Development Unit of Stockholm County Council. XLI: The costing was carried out on the same sample of patients as that used in the effectiveness analysis. XOP: Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for informationCullberg J, Levander S, Holmqvist R, et al. One-year outcome in first episode psychosis patients in the Swedish Parachute project. Acta Psychiatr Scand 2002;106:276-85.Petersen L, Jeppesen P, Thorup A, et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005;331:602.Malm U, Ivarsson B, Allebeck P, Falloon IR. Integrated care in schizophrenia: a 2-year randomized controlled study of two community-based treatment programs. Acta Psychiatr Scand 2003;107:415-23. XRE: GAF scores improved after 3 years in all groups, from 31.8 (+/- 7.3) to 58.2 (+/- 15.9) in the Parachute Project group, from 31.2 (+/- 9.7) to 57.6 (+/- 13.4) in the prospective group, and from 29.5 (+/- 10.0) to 47.6 (+/- 13.3) in the historical group. The differences between the Parachute Project group and the prospective group did not reach statistical significance. The Parachute Project group performed significantly better then the historical group after 12 and 36 months, (p<0.01 and p=0.001, respectively).Symptoms and working capacity were comparable across the three groups.The proportion of patients on disability allowance in the third year was 38% in the Parachute Project group, 36% in the prospective group, and 59% in the historical group. Both the Parachute Project group and the prospective group did significantly better than the historical group, (p<0.05).One of the 71 patients in the Parachute Project group committed suicide, compared with 2 of the 49 patients in the historical group and none of the 29 patients in the prospective group.On a scale ranging from 1 (low satisfaction) to 5 (very high satisfaction), mean subjective satisfaction with care was 4.1 (+/- 0.8) (median 4.2) for patients and 3.7 (+/- 0.9) (median 3.9) for relatives in the Parachute Project group. XSM: Power calculations were not reported and were probably not performed. Of the 71 patients (mean age at admission 27.7 years; 62% men) with a diagnosis of schizophrenia syndrome included in the Parachute Project, 61 had complete follow-up data and were included in the effectiveness study. Patients in the historical group comprised all first episode schizophrenia syndrome patients from three of those Stockholm areas participating in the Parachute Project 5 years later. Of the 29 patients (mean age at admission 28.1 years; 52% men) that were initially included, data were available for 25 patients. Finally, patients in the prospective comparison group came from the Uppsala University Psychiatric Clinic. Of the 43 patients (mean age at admission 29.3 years; 49% men) eligible patients, 41 had data available. XCO: The indirect costs were not considered in the economic analysis. XCU: US dollars ($). XSA: Statistical analyses (Mann-Whitney tests) were carried out to test the statistical significance of cost-differences between the Parachute Project group and the prospective group. The costs were presented as mean and median values, owing to the skewed data. XSY: Sensitivity analyses were not performed. XEB: See the 'Effectiveness Results' section. XCR: In the first year, the total median costs per patient were $11,614 (mean 23,192) in the Parachute Project group and $23,192 (mean 32,896) in the prospective group, (p<0.05).In the second year, the total median costs per patient were $533 (mean 9,076) in the Parachute Project group and $474 (mean 19,992) in the prospective group, (p not significant).In the third year, the total median costs per patient were $385 (mean 7,720) in the Parachute Project group and $1,126 (mean 18,632) in the prospective group, (p not significant). XCB: A synthesis of the costs and benefits was not relevant as a cost-consequences analysis was undertaken. XAU: The "Parachute Project" was a feasible, effective, and economically affordable treatment for first episode psychotic (FEP) patients with schizophrenia in Sweden. Cost-savings associated with the new intervention mainly arose from fewer inpatient days in comparison with more conventional treatments, during the first year of treatment. CO1: Sweden XIM: The study results would appear to support the Parachute Project, which consisted of a need-adapted treatment model for FEP patients with schizophrenia. KWO: Adult; Ambulatory Care /economics; Cohort Studies; Episode of Care; Feasibility Studies; Female; Follow-Up Studies; Health Care Costs; Hospitalization /economics; Humans; Male; Mental Health Services /economics; Prospective Studies; Schizophrenia /economics /epidemiology /therapy; Sweden /epidemiology; Time Factors XAC: 22006001932 XID: 31 Mar 2007 XLA: English XPR: 16968365 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22006001932 Record #24 %%%% DOI: 10.1001/archpsyc.63.10.1079 TTL: Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1) AUT: Jones P B, Barnes T R, Davies L, Dunn G, Lloyd H, Hayhurst K P, Murray R M, Markwick A, Lewis S W XSO: Archives of General Psychiatry XYR: 2006 VOL: 63(10) PAG: 1079-1087 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study compared first-generation (typical) antipsychotic (FGAs) drugs with second-generation (atypical) antipsychotics (SGAs) (other than clozapine). The FGAs comprised chlorpromazine hydrochloride, flupenthixol, haloperidol, loxapine, methotrimeprazine, sulpiride, trifluoperazine hydrochloride, zuclopenthixol, and the depot preparations of fluphenazine decanoate, flupentixol decanoate, haloperidol decanoate, pipothiazine palmitate and zuclopenthixol decanoate. The SGAs comprised risperidone, olanzapine, amisulpride, zotepine and quetiapine fumarate. Ziprasidone was not included as a comparator as it was not licensed in the authors' setting. XTI: Treatment. XEC: Cost-effectiveness analysis. XPA: The study population comprised patients with schizophrenia, aged between 18 and 65 years, whose psychiatrist chose to change current FGA or SGA drug treatment due to adverse effects or insufficient response. Further inclusion criteria were Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia, schizoaffective disorder, or delusional disorder. The patients included in the study were suffering for at least one month from positive psychotic symptoms. Patients under substance misuse, those suffering from medical disorders causally correlated with positive psychotic symptoms, and patients with a history of neuroleptic malignant syndrome were excluded from the study. XSG: The setting was secondary care, namely five medical schools covering 14 NHS Trusts in north western England, Nottingham, western London, south eastern London and Cambridge. The economic study was carried out in the UK. XDD: The patients were recruited between 12 July 1999 and 18 January 2002 and were followed up for up to 52 weeks. The dates of the cost data were not reported. The price year was also not reported. XDR: The health service costs included in the analysis were for hospital inpatient and outpatient services, primary and community care services, and prescribed drugs. The cost categories, quantities of resources used and unit costs were not reported. The resource use data were derived from the effectiveness study. However, the sources of the cost data and the price year were not reported. Discounting was not relevant as the costs were incurred during less than 2 years. XMB: The authors did not derive a summary benefit in the economic analysis. As the analysis demonstrated equal effectiveness of the two treatment options, a cost-minimisation analysis was performed. A benefit that was not combined with the costs was quality of life. This was assessed at baseline, and at 12, 26 and 52 weeks using QLS. The analysis was carried out on available quality of life data using a longitudinal analysis of covariance. XSD: The analysis was based on a multi-centre, rater-blinded, randomised controlled trial. The patients were followed up at baseline, and at 12, 26 and 52 weeks. They were assumed to have been lost to follow-up if they missed a minimum of four visits. At the end of the 52 weeks, 3 patients in each group had died, 11 (5%) were lost to follow-up and 22 (10%) were removed from the study.Randomisation was achieved after baseline assessment through a distant telephone service. Stratification was conducted per treatment centre and the patients were randomised using commuted blocks within strata. Clinicians blinded to the intervention conducted assessments at baseline, 12, 26 and 52 weeks. Blinding was achieved by isolating assessors and obstructing their contact with team members, by applying passwords for electronic data, by encrypting e-mails for randomisation, by avoiding discussions about patients with research teams, and by keeping case report forms inaccessible. XSS: The effectiveness data were derived from a single study. OI: The authors compared their findings with those from other studies and showed them generally to be in agreement. The issue of generalisability of the results was not directly addressed. The authors did not present their results selectively and the results from the statistical tests were well reported. However, the cost analysis was not well documented. The study considered adult patients with schizophrenia, whose medical treatment was changed because of adverse events or low efficacy, and this was reflected in the authors' conclusions. One of the limitations of the study was the lack of a more robust valuation tool for the quality of life of patients with schizophrenia. In addition, the design of the study did not allow for within-group comparisons of different drugs within the same drug category. Finally, a sub-group analysis of patients with different characteristics (e.g. specified clinical symptoms, different duration of illness) was not performed. SCO: The selection of the comparators was explicitly justified. The authors, in accordance with clinical guidelines in their setting, compared two broad drug categories (i.e. first- versus second-generation antipsychotic drugs) and not individual drugs. You should decide if the comparators used comprise a widely used technology in your own setting. VB: The authors did not use a summary measure of benefit in the economic analysis. As equal effectiveness was demonstrated, a cost-minimisation analysis was performed. VC: The cost analysis was subject to a number of deficiencies. The cost and resource categories included were unclear and were not reported separately. In addition, the sources of the cost data, the conversion rates and the price year were not reported and no statistical or sensitivity analysis of the costs was carried out. These factors will have introduced uncertainty into the results, will make the analysis difficult to rework for other settings, and will limit the interpretation of study findings. VM: The analysis was based on a multi-centre, rater-blinded, randomised controlled trial. This seems to have been appropriate given the study question. The study sample was representative of the study population and the patient groups were comparable at analysis. The methods of randomisation, blinding, length of study and loss to follow-up were all reported, suggesting that the internal validity of the study is likely to be good. In addition, an extensive statistical analysis was undertaken to deal with potential biases and confounding factors. Power calculations were conducted, but the power of the study was lower than anticipated (75% versus 80%) in the planning phase for the detection of expected differences in QLS score. However, this smaller sample size is unlikely to have affected the results. XAE: The analysis was conducted on an intention to treat basis. Those lost to follow-up were accounted for using multiple imputations. Data were analysed using SPSS for Windows 10 (SPSS Inc., Chicago) and Stata Version 7 (StataCorp, College Station). The statistical analysis demonstrated that the patient groups were comparable in terms of their demographic and clinical characteristics. The secondary outcomes included:patient syndromes, as assessed using the Positive and Negative Syndrome Scale score;the Calgary Depression Scale score;participant attitudes and adherence ratings;the Global Assessment of Functioning Scale score;the Adverse Effects Rating Scale scores; andcases of polypharmacy.In addition, the participants' satisfaction with the new antipsychotic medication was assessed at 12 and 52 weeks. XCL: The use of SGAs or FGAs as options for the treatment of patients with schizophrenia, whose drug treatment was altered for clinical reasons, resulted in similar efficacy for adverse effects, symptoms and patient satisfaction. XDI: Mental disorders. XFU: None stated. XLI: It would appear that costing was carried out prospectively on the same sample of patients as that used in the effectiveness study. XOP: Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information. XRE: The analysis demonstrated that the intervention groups had no statistical differences in health outcomes. Differences in patient satisfaction between the two groups were assessed using the Mann-Whitney test, which demonstrated that the patients were indifferent to drug treatment.Similarly, in relation to polypharmacy, differences between the two groups before randomisation and at 52 weeks were not statistically significant. In addition, even though more patients in the SGA group continued with the assigned treatment than those in the FGA group, the difference was not statistically significant (65% versus 54%; p=0.1). XSM: Power calculations demonstrated that a sample of at least 110 participants per treatment arm was required to find a difference in the Quality of Life Scale score (QLS) of 5 points, assuming a statistical power of 80%, 95% confidence, 2-tailed assumptions and a follow-up rate of 75%. Initially, 275 patients were referred from the five centres. Of these, 9 (3%) were ineligible, 1 (0.4%) was unable to give consent and 36 (13%) refused consent, while 2 psychiatrists withdrew one referral each (1%). Overall, 227 patients (referred by 73 psychiatrists) were randomly assigned to the FGA group (n=118) and to the SGA group (109). XCO: The indirect costs were not included in the analysis. XCU: UK pounds sterling () and US dollars ($). A conversion rate was not reported. XSA: No statistical analysis of the costs was reported. XSY: The authors conducted sensitivity analyses to investigate the impact of interchanging between treatment options during the first 12 weeks. Applying a 12-week horizon, the analysis was first performed on all patients. A second protocol analysis was conducted in which all patients who changed treatment arms before the end of 12 weeks were excluded from the analysis. To account for missing values on the QLS, the authors conducted multiple imputations. XEB: Although FGAs seem to have shown better results for QLS scores, differences between the two treatment arms were not statistically significant, (p=0.24). XCR: At 52 weeks, the mean total costs were lower in the FGA group ($34,750, standard deviation, SD=48,100; 18,800, 26,000) than in the SGA group ($37,185, SD=46,250; 20,100, SD=25,000). XCB: The costs and benefits were not combined. As equal effectiveness was demonstrated in the clinical study, a cost-minimisation analysis was performed. XAU: "In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs (first-generation antipsychotics) rather than nonclozapine SGAs (second-generation antipsychotics)." CO1: United Kingdom XIM: The authors made no explicit recommendations for changes in policy or practice. The analysis indicates areas where more research-based information is needed (e.g. comparisons within drug categories, sub-group analysis of patient groups, analysis on a greater sample size). KWO: Adolescent; Adult; Antipsychotic Agents /adverse effects /classification /therapeutic use; Cost-Benefit Analysis; England; Female; Follow-Up Studies; Health Care Costs; Humans; Male; Middle Aged; Patient Satisfaction; Practice Patterns, Physicians' /statistics & numerical data; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia /drug therapy; Treatment Outcome XAC: 22006002056 XID: 30 Apr 2007 XLA: English XPR: 17015810 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22006002056 Record #25 %%%% DOI: 10.1192/bjp.bp.106.028654 TTL: Cost-effectiveness of first- v second-generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy AUT: Davies L M, Lewis S, Jones P B, Barnes T R, Gaughran F, Hayhurst K, Markwick A, Lloyd H XSO: British Journal of Psychiatry XYR: 2007 VOL: 191 PAG: 14-22 XPT: Journal article XST: This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. XHT: The study examined the use of first- versus second-generation antipsychotic drugs for patients with schizophrenia requiring a change of treatment because of poor response to previous therapy. The drugs included in the group of first-generation antipsychotics (FGAs) were chlorpromazine, flupentixol, haloperidol, loxapine, sulpiride, trifluoperazine and zuclopenthixol, plus depot antipsychotics (fluphenazine, zuclopenthixol, flupentixol and haloperidol decanoate). The drugs included in the group of second-generation antipsychotics (SGAs) were risperidone, olanzapine, amisulpride and quetiapine. XTI: Treatment. XEC: Cost-utility analysis. XPA: The study population comprised patients with schizophrenia for whom a change in antipsychotic drug treatment was being considered because of intolerance or insufficient clinical improvement, and for whom a choice between an FGA and an SGA other than clozapine was relevant. The inclusion criteria were a DSM-IV diagnosis of schizophrenia, schizo-affective disorder or delusional disorder, age 18 to 65 years, and an interval of at least 1 month since the first onset of positive psychotic symptoms. The exclusion criteria were substance misuse or a medical disorder considered, clinically, to be the major cause of positive psychotic symptoms, or a history of neuroleptic malignant syndrome. XSG: The setting was secondary care. The economic study was carried out in the UK. XDD: The clinical and economic data were derived from a study published in 2006. The costs were expressed using 2001/02 prices. XDR: The viewpoint of the analysis was that of the NHS, social support services and the patient. The health services included in the analysis were hospital inpatient and outpatient services, primary and community care, and prescribed medications. Details of the quantities of resources used, but not unit costs, were given. The total costs per category were presented at 12, 24 and 52 weeks. Resource consumption was based on data derived directly from the clinical trial using patient records and case-note reviews. Three methods of data collection were applied in order to derive the most accurate estimates of service use. The costs of the drugs, excluding dispensing and administration, came from the British National Formulary. Other costs were derived from the Personal Social Services Research Unit, as well as from other national sources. Discounting was not relevant given the 1-year timeframe of the analysis. The costs were standardised to 2001/02 prices using the health service price index when required. XMB: The summary benefit measure used was the quality-adjusted life-years (QALYs). These were estimated directly using the utility values derived from the clinical trial. Discounting was not performed because of the short-term time horizon. XSD: This was a multi-centre, open, rater-blind, randomised controlled trial that was conducted in five centres in England, covering 14 NHS trusts. The length of follow-up was one year. Clinical data were available for 185 patients at the end of follow-up. Clinicians were asked to try to keep participating patients on the randomised medication for at least 12 weeks. The clinical outcomes were evaluated through patient questionnaires at 12, 24 and 52 weeks' follow-up. Both patients and physicians were aware of the treatment delivered. However, masked independent assessments were performed. OI: The authors stated that their findings agreed with the conclusions of two UK-based economic modelling studies, although many studies suggest that SGAs may be cost-effective. The authors noted that the issue of missing clinical and economic data could have affected the robustness of the analysis, although the sensitivity analysis showed that the use of alternative imputation methods did not alter the results of the study. In addition, extensive statistical tests were carried out to address the issue of uncertainty. Another drawback of the analysis was the fact that the study had insufficient power to detect statistically significant differences in QALYs and costs. SCO: The rationale for the choice of the comparators was clear. Newer antipsychotics were compared with conventional drugs. A list of drugs included in each category was provided. Clozapine was not considered. You should decide whether they are valid comparators in your own setting. VB: QALYs are an appropriate benefit measure of the impact of the interventions on patient health since the analysis focused on health-related quality of life, which is a relevant dimension of health for patients with schizophrenia. QALYs are also comparable with the benefits of other health care interventions. The authors stated that the EQ-5D is a validated instrument for people with schizophrenia. VC: The analysis of the costs was consistent with the perspective adopted in the study. A breakdown of the cost items was given. Extensive details of resource quantities were provided, but the unit costs were not reported. The costs were derived from typical UK sources and the use of alternative sources was investigated in the sensitivity analysis. Statistical analyses were carried out to deal with the skewed distributions of the resources used. The price year was reported, thus facilitating reflation exercises in other time periods. The authors stated that the exclusion of costs of contacts with the criminal justice system, use of residential accommodation and informal care, might have resulted in an underestimation of total costs, although the amount of these items should have been limited over the trial observation period. XSM: The authors stated that the study had a 75% power to detect statistically significant differences between groups in the primary clinical outcome. Of the initial sample of 275 patients referred, 227 (82%) were included. There were 118 patients in the group using FGAs and 109 patients in the group using SGAs. The mean age was 40.5 (+/- 11.3) years in the FGA group and 40.9 (+/- 11.1) years in the SGA group. The proportions of male participants were 69% (FGA group) and 67% (SGA group), respectively. VM: The clinical evidence came from a clinical trial, which was appropriate for the study question. The use of assessment blinding and intention to treat analysis, and the multi-centre nature of the study enhances the internal validity of the analysis. However, neither the patients nor the physicians were blinded to treatment allocation, which could have introduced some bias, for example in the interpretation of side effects. Nevertheless, the authors pointed out that this should have favoured newer drugs. Further, the study was powered to detect statistically significant differences between the groups. The study groups were balanced at baseline, which improves the validity of the comparison. Statistical analyses were carried out to account for the potential impact of confounding factors, such as some baseline characteristics of the patients enrolled. Statistical techniques were used to take missing data into consideration. More details of the clinical trial might be found in the primary publication. A limitation of the clinical analysis was that, as the authors noted, there was insufficient information to determine whether the patients who participated in the trial were representative of eligible patients requiring a change in medication. Thus, caution will be required when considering the representativeness of this patient population. XAE: The primary outcome measure was the score on the Quality of Life Scale (QLS). The EuroQol (EQ-5D) was also used for the current economic evaluation. The analysis of the clinical study was conducted on an intention to treat basis. At baseline, the two study groups were comparable with respect to their clinical and demographic characteristics. Missing values for patients who completed the scheduled follow-up but had missing observations were imputed using linear interpolation. Patients with one or more missing observations at the end of follow-up were treated as censored cases. XCL: The effectiveness analysis showed that health-related utility improved in both groups. XDI: Mental disorders. XFU: Funding received from the Secretary of State for Health (UK). XLI: The costing was performed prospectively on the same sample of patients as that used in the effectiveness analysis. XOP: Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.Jones PB, Davies LM, Barnes TR, et al. Randomized controlled trial of effect on quality of life of second generation versus first generation antipsychotic drugs in schizophrenia. Arch Gen Psychiatry 2006;63:1079-87.Bagnall AM, Jones L, Ginnelly L, et al. A systematic review of atypical antipsychotic drugs in schizophrenia. Health Technol Assess 2003;7(13):1-204.Palmer CS, Brunner E, Ruiz-Flores LG, et al. A cost effectiveness decision analysis model for treatment of schizophrenia. Arch Med Res 2002;33:572-80.Almond S, O'Donnell O. Cost analysis of the treatment of schizophrenia in the UK: a simulation model comparing olanzapine risperidone and haloperidol. Pharmacoeconomics 2000;17:383-9. XRE: The utility values changed from 0.67 (+/- 0.29) at baseline to 0.78 (+/- 0.22) in the FGA group, and from 0.61 (+/- 0.33) to 0.75 (+/- 0.23) in the SGA group. XCO: Productivity costs were not included. XCU: UK pounds sterling (). XSA: The total costs were presented as mean values with standard deviations. XSY: The issue of uncertainty was addressed in a bootstrap analysis that generated cost-effectiveness acceptability curves. The net benefit was also calculated, which provided an estimate of the monetary value of a QALY at different values of societal willingness-to-pay. The incremental costs and QALYs were estimated by analysis of covariance, using a general linear model and covariates of baseline QLS score, utility, psychiatric hospital inpatient and outpatient costs prior to enrolment in the trial, and trial centre. Alternative sources of the costs for psychiatric services were considered in the sensitivity analysis. The impact of different imputation methods for missing values was also tested. XEB: After one year of treatment, the expected QALYs were 0.74 (+/- 0.22) in the FGA group and 0.67 (+/- 0.25) in the SGA group.When adjusted for covariates, the difference in QALYs was 0.04 (+/- 0.03) in favour of the FGA group. XCR: Over the 12-month follow-up period, the total costs were 18,858 (+/- 28,602) in the FGA group and 20,118 (+/- 25,348) in the SGA group. Thus, there was a trend towards lower costs in the FGA group.The cost of antipsychotics represented only a small percentage of the overall costs (2% in the FGA group and 4% in the SGA group).Hospitalisations represented the largest category of costs. XCB: The costs and benefits were not combined in a cost-utility ratio as switching to FGAs produced more QALYs at lower costs than switching to SGAs, which was a dominated strategy.The sensitivity analysis indicated large standard errors associated with the difference in costs and QALYs, suggesting a high level of uncertainty. However, in all scenarios, FGAs dominated SGAs.The cost-effectiveness acceptability curve showed that, at a willingness-to-pay of 35,000 per QALY gained, the probability that FGAs were cost-effective was 75%, with an associated net benefit of 1,752.Overall, the probability that FGAs were cost-effective was between 54% (if decision-makers were willing to pay only 1 to gain one QALY) and 81% (if decision-makers were willing to pay up to 50,000 to gain one QALY). XAU: Conventional antipsychotics for the treatment of schizophrenia might be cost-effective in comparison with newer antipsychotics. CO1: United Kingdom XIM: The study results do not support the widespread use of SGAs for the treatment of schizophrenia. The authors concluded that "further observational and pragmatic trials are required to identify cost-effective antipsychotic use, the determinants of costs and outcomes and the roles of first- and second-generation antipsychotic drugs in long-term management". KWO: Adult; Antipsychotic Agents /economics /therapeutic use; Cost-Benefit Analysis; Female; Great Britain; Humans; Male; Quality-Adjusted Life Years; Schizophrenia /drug therapy /economics; Statistics as Topic XAC: 22007008152 XID: 31 Oct 2007 XLA: English XPR: 17602120 DBN: NHS EED RUR: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=22007008152