Use of surrogate outcomes in US FDA drug approvals, 2003-2012: a survey.
Bottom Line: To evaluate, across a spectrum of diseases, how often surrogate outcomes are used as a basis for drug approvals by the US Food and Drug Administration (FDA), and whether and how the rationale for using treatment effects on surrogates as predictors of treatment effects on patient-centred outcomes is discussed.For evaluating new drugs, patient-centred outcomes should be chosen whenever possible.If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study.
Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.Show MeSH
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Mentions: Sixty-eight of 1043 (7%) drug approvals were about COPD, diabetes, glaucoma or osteoporosis, and 58 (58/1043; 6%) of these were eligible for our study. The reasons for exclusion of approvals are summarised in figure 1. Of the 58 included approvals, 9 were for COPD (16%), 26 (45%) for diabetes, 9 (16%) for glaucoma and 14 (24%) for osteoporosis. For three of the four examined conditions, the drug approvals were mostly based only on a surrogate outcome (COPD (7/9 approvals were based only on a surrogate, 78%), diabetes (26/26 approvals, 100%) and glaucoma (9/9 approvals, 100%), see online supplementary table S1). COPD drug approvals were primarily based on the effects on improving lung function, with the exception of two drug approvals (SPIRIVA HANDIHALER and DALIRESP), which also examined COPD exacerbations. All diabetes drug approvals reviewed were based on lowering blood sugar level and all glaucoma drug approvals reviewed were based on lowering IOP. Most drug approvals for osteoporosis (10/14; 71%) were based on both, surrogate outcomes (bone mineral density) and patient-centred outcome (fractures).
Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.