Microsoft excel 2013

All analyses were stratified based on whether the novel drug was first approved by the FDA on the basis of a single pivotal trial, multiple pivotal trials that focused on surrogate markers of disease for the primary efficacy endpoint, or both (a single pivotal trial that focused on surrogate markers). We used descriptive statistics to summarize the characteristics, design features, and findings of each study, as well as sample characteristics, aggregate number of trials, number of patients enrolled, and patient years of observation for each indication. We used χ², Wilcoxon’s rank sum, and Kruskal-Wallis tests to examine differences across the three categories of approval. We used χ² and Fisher’s test of exact probability to examine differences in study findings within categories, comparing studies using surrogate markers of disease and clinical outcomes as primary endpoints. Analyses were repeated, stratifying by year of indication approval, therapeutic area, and expected length of treatment. All analyses were performed using Microsoft Excel 2013 and JMP 7.0.1 (SAS Institute; Cary, NC). All statistical tests were two tailed and used a type I error rate of 0.005 to account for the 10 comparisons made across categories of indication approval.