In both GWAS and OMIM datasets, our estimates of the effect of genetic evidence on Phase I to II progression probabilities are lower than originally reported, and confidence intervals sometimes exclude original estimates. With some exceptions (e.g. oncology studies), Phase I trials assess safety in healthy volunteers, not efficacy, so their success may be less closely linked to human genetic evidence for target involvement in disease. Validation sets may also differ systematically from the 2013 training data. For example, it is possible that there are systematic differences in the types of associations discovered before and after 2013 (New Genetic validation set). Later associations may be biased towards those with smaller effect sizes or rarer variants only detectable in larger cohorts, and could also be less predictive of drug efficacy. Using the complete updated dataset (Full Data), including all Pharmaprojects drugs and pre and post 2013 genetic associations, we find the estimated effect of GWAS genetic evidence on Phase I to Approval is still significantly positive, and the effect of OMIM genetic evidence is greater than originally reported.
