Re: Shrinking MACE event rate
in response to
by
posted on
Jan 20, 2019 09:22AM
This is from a draft document from the FDA. I can't find a finalized document. It's a good reminder of the limitations of post hoc data analyses (bolding mine).
Multiple Endpoints in Clinical Trials Guidance for Industry
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
"....In the past, it was not uncommon, after the study was unblinded and analyzed, to see a variety of post hoc adjustments of design features (e.g., endpoints, analyses), usually plausible on their face, to attempt to elicit a positive study result from a failed study--a practice sometimes referred to as data-dredging. Although post hoc analyses of trials that fail on their prospectively specified endpoints may be useful for generating hypotheses for future testing, they do not yield definitive results. The results of such analyses can be biased because the choice of analyses can be influenced by a desire for success. The results also represent a multiplicity problem because there is no way to know how many different analyses were performed and there is no credible way to correct for the multiplicity of statistical analyses and control the Type I error rate. Consequently, post hoc analyses by themselves cannot establish effectiveness. Also, additional endpoints that have not been pre-specified or evaluated with adjustment for multiplicity when required cannot, in general, be used to demonstrate an effect of the drug, even in successful studies...."