Sources of Safety Data and Statistical Strategies for Design and Analysis: Clinical Trials

Background: There has been an increased emphasis on the proactive and comprehensive evaluation of safety endpoints to ensure patient well-being throughout the medical product life cycle. In fact, depending on the severity of the underlying disease, it is important to plan for a comprehensive safety evaluation at the start of any development program. Statisticians should be intimately involved in this process and contribute their expertise to study design, safety data collection, analysis, reporting (including data visualization), and interpretation. Methods: In this manuscript, we review the challenges associated with the analysis of safety endpoints and describe the safety data that are available to influence the design and analysis of premarket clinical trials. Results: We share our recommendations for the statistical and graphical methodologies necessary to appropriately analyze, report, and interpret safety outcomes, and we discuss the advantages and disadvantages of safety data obtained from clinical trials compared to other sources. Conclusions: Clinical trials are an important source of safety data that contribute to the totality of safety information available to generate evidence for regulators, sponsors, payers, physicians, and patients. This work is a result of the efforts of the American Statistical Association Biopharmaceutical Section Safety Working Group.