Safety Assessment Versus Efficacy Assessment

摘要

Many statistical methods have been developed that focus primarily on efficacy. Safety evaluation frequently involves many additional considerations. Randomized controlled trials, especially later phase 3 trials, are infrequently designed based on safety outcomes. Most of these trials are designed based on efficacy outcomes, and therefore have limited power to detect important differences in safety outcomes. Recently, there have been calls to design trials with sufficient power to address known safety concerns. When prevention trials introduce an experimental preventive intervention (e.g., a vaccine) to an otherwise healthy (although at-risk) population, safety considerations can substantially affect the benefit:risk ratio and thus the utility and acceptability of the intervention. Observation of safety outcomes is often less controlled than for efficacy outcomes, particularly for safety concerns that emerge during the course of the trial. When either safety or efficacy outcomes are missing, specific assumptions are required for analysis (e.g., missing completely at random, MCAR), but often these assumptions may not apply. The statistical methods that rely on these assumptions have largely been developed with a focus on efficacy outcomes. Illustrative examples, including meta-analyses, will be presented and the underdeveloped areas highlighted.