Abstract

This review aimed to compare the predictive value between the untreated reduction in intraocular pressure (IOP) from baseline or placebo measured in early phase clinical trials to phase III and IV results for glaucoma medicines. Published, placebo-controlled, randomised, parallel, single-masked or double-masked clinical trials with at least one phase II, III and IV study available were reviewed. This study included 50 articles evaluating 9 medicines from 59 active arms and 18 placebo arms. For all studies the phase II IOP reduction from placebo showed less decrease compared to the decrease from baseline (p<0.04). For all medicines, reductions from morning baseline in phase II did not predict better than the decrease from placebo for phase III (p=0.15) or IV (p=0.08) reductions in IOP. In contrast, diurnal IOP reduction from baseline in phase II predicted decreases better than placebo in phase III (p=0.007) and IV (p=0.02). Generally, for prostaglandins, β blockers and carbonic anhydrase inhibitors for the morning trough and diurnal curve there was no difference in pressure reduction from baseline for phase II compared to phase III or IV (p≥0.23). In contrast, where comparisons were available for the decrease in pressure from placebo there were differences for phase II compared to phase III and phase IV (p≤0.02). This study suggests that in early phase glaucoma trials, using the reduction from untreated baseline in general better approximates the results of later regulatory and post-commercialisation trials than the decrease from placebo.