Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study: lessons from Pre-RELAX-AHF.

ABSTRACT:

Background

Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory studies. Although observing an effect on one of many endpoints due to chance is likely, observing concurrent positive trends across several outcomes by chance is usually unlikely.

Methods

Pre-RELAX-AHF, which compared 4 relaxin doses with placebo in AHF, has shown favourable trends versus placebo (one-sided P < 0.10) on six of nine clinical endpoints in the 30 μg/kg/day group. To illustrate evaluation of multiple, correlated clinical endpoints for evidence of efficacy a

SUBMITTER: Davison BA 

PROVIDER: S-EPMC3167045 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature