Sample size re-estimation after interim analysis

JoakimE — Wed, 12 Jun 2024 10:59:04 GMT

Hi,

My question concerns statistical theory and not SAS per se. However, there are a lot of qualified statisticians on this forum, so I hope no one takes offence in me posting this here 😊

Background:
I am working with a clinical study that includes one interim analysis ¾-way into the trial in addition to the final analysis at the end. At the interim analysis (using data from 60 subjects), the primary endpoint variable was tested with a hypothesis test at a very low alpha of 0.1%, conserving the rest of the alpha (4.9%) to the final analysis (the O’brien-Fleming method). The study protocol stipulates that the study should be stopped in case the interim analysis is significant. Otherwise, the sample size should be re-estimated based on the interim analysis findings. The target number of subjects at the end of trial is currently 80, as specified in the protocol.

Result:
The result of the interim hypothesis test yielded a p-value of around 0.017. Hence, a very promising result, although, not significant at the predefined alpha for the interim analysis.

Questions:
Can the study be stopped now? I assume no, since we did not meet the 0.1% alpha level in the interim analysis. However, clearly, if the study was stopped, significance would be attained, since there is 4.9% alpha remaining. Can there be grounds to let the study continue, but not all the way to 80 subjects? I.e. this would amount to a decrease in sample size as a result of the sample size re-estimation. However, it is not clear to me how that can be done. I could perform a conditional power calculation, but to my knowledge this only serves to answer the question of the original target sample size would be enough or if it needs to be increased. I assume I cannot use this framework to decrease the sample size?

Thanks in advance for any input.

topic Sample size re-estimation after interim analysis in Statistical Procedures

Sample size re-estimation after interim analysis