Chunk #4 — Bias in a protocol for a meta-analysis of 5-HTTLPR, stress, and depression — Issue 1: “Primary Analysis Plan 2” to study lifetime depression does not allow for establishing temporal order between stress and depression
proposed meta-analysis, GxE research, the poor accuracy of these retrospective recall measures is particularly important. Simulation studies reveal that the difference between measurements that are unreliable (correlation with true score = 0.4) vs reliable (0.7) corresponds to a large difference in sample size. Thus, although measuring environmental exposure is costly, doing it well can pay for itself by reducing sample size [12]. However, our concern is that lifetime measures of stress and depression in the forthcoming meta-analysis are not merely unreliable, they are also invalid, and therefore they contaminate the meta-analysis with misinformation. Increased power afforded by larger N sometimes counterveils unreliable measurement, but large N cannot counterveil invalid data. Unfortunately, the biasing influence of invalid data in a meta-analysis is exacerbated by large samples.