Risk ratios for progressing from Phase x to Phase y, x > y were computed as P(Success|GeneticEvidence)P(Success|NoGeneticEvidence)=Ng,x/Ng,yNg′,x/Ng′,y where Ng,x=∑i=1nED(gi,ti)I(hi≥x) is the number of gene target-indication pairs in Phase x or later with genetic evidence and Ng′,x=∑i=1n(1-ED(gi,ti))I(hi≥x) is the number of gene target-indication pairs in Phase x or later without genetic evidence. We required at least 5 reported genetic associations for similar traits. Phase progression probability calculations usually exclude in progress development [18] but here we include them for consistency with Nelson et al. Confidence intervals were computed using the riskratio.boot function in the epitools R package [32]. We ensured consistency of this approach with that of Nelson et al. by verifying our code could reproduce their results from supplemental materials (S1 Text). Drugs approved only outside the US and EU and drugs with unknown latest phase were excluded from this analysis.
