The FDA asked us to use a method other than Wald and strongly suggested that we use Miettinen-Nurminen 1985 (MN) for computing confidence limits (CL) at summary level. This method is becoming increasingly popular and is used by many pharmaceutical companies, including Merck, Abbvie, and Moderna (cf. simple Google search).
SAS has provided a partial implementation of MN scoring through COMMONRISKDIFF(CL=score) where the within-stratum calculation follows MN 1985 but inverse-variance stratum weights are used at the summary level. This method comes from the 2013 Agresti book. Has this method ever been published in a peer-reviewed article? Has it ever been used in a clinical trial submission? Is this method popular, i.e., number of citations? The lack of visibility in the use of this "SCORE" method prevent the use of this algorithm in a submission to health authorities.
The current alternative is to use R. Indeed, two packages have been developed to calculate CL based on MN 1985 method: metalite.ae (Merck) and scoreci. SAS users have already written about this 4 years ago.
I am a biostatistical manager at Bristol Myers Squibb. This issue has risen to the VP level as we plan to adopt MN 1985 in all our submissions in all the therapeutic areas. Confidence limits play an important role because they influence key analyses such as futility analysis for the primary outcome.
Will you provide this algorithm and if so, when?
