Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘positive results on only one of several variables, thereby reducing the overallType I error quite substantially.Just wait for the results and then decideThe last strategy is to do nothing to correct for inflated Type I error, to test eachcomparison at the 5% level of significance, and, whenever appropriate, to addcautions to the trial report warning of the potential effects of multiple testing [11].The problem with this strategy is that it puts the burden on the reader to assesswhether any positive results generated from the trial are valid, or are likely to bedue to the spurious output of multiple testing. This approach can be attractivewhen the outcome variables are expected to be highly associated, and can be usedas an alternative or as a supplement to the second strategy described above.The current practice of medical journals is not to demand any correction formultiple testing. A balanced caution in the interpretation of the usually largenumber of statistical tests performed is preferred to undue flexibility in suppressingunexpected findings.Specific strategies for dealing with several endpointsMultiple endpoints exist in almost every trial. We will now discuss somespecific methods based on the strategies mentioned above, which are used todeal with several endpoints. They all demonstrate that a possible loss ofdetailed information has to be weighed against a gain in terms of reducingfalse-positive findings.Specify the priorities of the endpoints in advanceThis approach is most commonly applied in clinical trials practice. One exampleis the previously mentioned World Health Organization trial of emergencycontraception [6]. The trial protocol prespecified the sequence of planned analysesand defined primary and secondary endpoints. The primary endpoint in this trialwas unintended pregnancy, and the secondary endpoints were side-effects due tothe various treatments. The main conclusion of the trial with respect to the primaryendpoint was that there was no evidence for a difference between the varioushormonal methods of emergency contraception with respect to unintendedpregnancies. As mentioned above, treatments differed in their side-effect profiles,with less menstrual bleeding under mifepristone. The main conclusion was that allstudied regimes seem to be efficacious for emergency contraception.Combine outcomes into a single summary statisticA quality of life questionnaire is a classic example of a summary endpoint thatsynthesizes a large amount of information into a single measure (score) of335