Published registry-based pharmacoepidemiologic associations show limited concordance with agnostic medication-wide analyses

Abstract

ObjectivesTo assess how the results of published national registry-based pharmacoepidemiology studies (where select associations are of interest) compare with an agnostic medication-wide approach (where all possible drug associations are tested). Study Design and SettingWe systematically searched for publications that reported drug associations with any, breast, colon/colorectal, or prostate cancer in the Swedish Prescribed Drug Registry. Results were compared against a previously performed agnostic medication-wide study on the same registry. Protocol: https://osf.io/kqj8n. ResultsMost published studies (25/32) investigated previously reported associations. 421/913 (46%) associations had statistically significant results. 134 of the 162 unique drug-cancer associations could be paired with 70 associations in the agnostic study (corresponding drug categories and cancer types). Published studies reported smaller effect sizes and absolute effect sizes than the agnostic study, and generally used more adjustments. Agnostic analyses were less likely to report statistically significant protective associations (based on a multiplicity-corrected threshold) than their paired associations in published studies (McNemar odds ratio 0.13, P = 0.0022). Among 162 published associations, 36 (22%) showed increased risk signal and 25 (15%) protective signal at P < 0.05, while for agnostic associations, 237 (11%) showed increased risk signal and 108 (5%) protective signal at a multiplicity-corrected threshold. Associations belonging to drug categories targeted by individual published studies vs. nontargeted had smaller average effect sizes; smaller P values; and more frequent risk signals. ConclusionPublished pharmacoepidemiology studies using a national registry addressed mostly previously proposed associations, were mostly “negative”, and showed only modest concordance with their respective agnostic analyses in the same registry.