Chunk #7 — 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
We suspect that Plan 2 is retained solely because it offers an attention-getting large sample size. To quote Culverhouse et al. [1], “Our second set of primary analyses will involve larger sample sizes, including children and adults of all ages. The increase in sample size will result in increased power if there is a broad genetic association between 5-HTTLPR genotypes, stress, and depression. However, this comes at a cost; in these analyses, we give up the opportunity to investigate whether stress preceding depression was a potential cause of the depression, as relative timing of stress and depression may not be known, and thus will not be included in the models.” We anticipate that even if the more focused Analysis 1 (closer design replication, smaller N) shows evidence of the interaction, the results of Plan 2 (which is not a replication, but has a larger N) will be those most likely to be highlighted by the authors, covered in the media, and remembered by the public. Plan 2’s result will be rendered more salient to readers because of its anticipated sample
