Benefit-Risk Tradeoffs in Assessment of New Drugs and Devices

Circulation. 2020 Nov 17;142(20):1974-1988. doi: 10.1161/CIRCULATIONAHA.120.048933. Epub 2020 Nov 16.

Abstract

Balancing benefits and risks is a complex task that poses a major challenge, both to the approval of new medicines and devices by regulatory authorities and in therapeutic decision-making in practice. Several analysis methods and visualization tools have been developed to help evaluate and communicate whether the benefit-risk profile is favorable or unfavorable. In this White Paper, we describe approaches to benefit-risk assessment using qualitative approaches such as the Benefit Risk Action Team framework developed by the Pharmaceutical Research and Manufacturers of America, and the Benefit-Risk Framework developed by the United States Food and Drug Administration; and quantitative approaches such as the numbers needed to treat for benefit and harm, the benefit-risk ratio, and Incremental Net Benefit. We give illustrative examples of benefit-risk evaluations using 4 treatment interventions including sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes; a direct antithrombin agent, dabigatran, for reducing stroke and systemic embolism in patients with nonvalvular atrial fibrillation; transcatheter aortic valve replacement in patients with symptomatic severe aortic valve stenosis; and antiplatelet agents vorapaxar and prasugrel for reducing cardiovascular events in patients at high cardiovascular risk. Regular applications of structured benefit-risk assessment, whether qualitative, quantitative, or both, enabled by easy-to-understand graphical presentations that capture uncertainties around the benefit-risk metric, may aid shared decision-making and enhance transparency of those decisions.

Keywords: benefit–risk assessment; cardiovascular disease; clinical trial; evidence-based medicine; statistical analysis.

Publication types

  • Review

MeSH terms

  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Discovery*
  • Embolism / etiology
  • Embolism / metabolism
  • Embolism / prevention & control*
  • Equipment and Supplies*
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors
  • Sodium-Glucose Transport Proteins / metabolism
  • Stroke / etiology
  • Stroke / metabolism
  • Stroke / prevention & control*
  • United States
  • United States Food and Drug Administration

Substances

  • Fibrinolytic Agents
  • Hypoglycemic Agents
  • Platelet Aggregation Inhibitors
  • Sodium-Glucose Transport Proteins