Referee report. For: Using multiple outcomes in intervention studies: improving power while controlling type I errors [version 2; peer review: 1 approved, 1 not approved]

Daniel Lakens
The CONSORT guidelines for clinical trials recommend using a single primary outcome, to guard against excess false positive findings when multiple measures are considered. However, statistical power can be increased while controlling the familywise error rate if multiple outcomes are included. The MEff statistic is well-suited to this purpose, but is not well-known outside genetics. Methods Data were simulated for an intervention study, with a given sample size (N), effect size (E) and
more » ... on matrix for a suite of outcomes (R ). Using the variance of eigenvalues from the correlation matrix, we compute MEff, the effective number of variables that the alpha level should be divided by to control the familywise error rate. Various scenarios are simulated to consider how MEff is affected by the pattern of pairwise correlations within a set of outcomes. The power of the MEff approach is compared to Bonferroni correction, and a principal component analysis (PCA). Results In many situations, power can be increased by inclusion of multiple outcomes. Differences in power between MEff and Bonferroni correction are small if intercorrelations between outcomes are low, but the advantage of MEff is more evident as intercorrelations increase. PCA is superior in cases where the impact on outcomes is fairly uniform, but MEff is applicable when intervention effects are inconsistent across measures. Conclusions The optimal method for correcting for multiple testing depends on the underlying data structure, with PCA being superior if outcomes are all indicators of a common underlying factor. Both Bonferroni correction and MEff can be applied post hoc to evaluate published intervention studies, with MEff being superior when outcomes are moderately or highly correlated. A lookup table is provided to give alpha levels for
doi:10.5256/f1000research.141308.r160159 fatcat:tcex3u4edzbrvcm6i3dhmqwmii