FDA Guidance on Benefit-Risk Assessment

The U.S. Food and Drug Administration (FDA) has issued draft guidance to clarify how benefit-risk assessment (BRA) considerations are integrated into the agency’s premarket and postmarket decisions for new drugs and biologics marketing applications.

According to the FDA, BRA considers in addition to the extensive safety and effectiveness evidence presented, other factors such as the nature and severity of the condition that the product is intended to treat or prevent, the benefits and risks of other available therapies for the disease, and risk management tools that may be needed to ensure that the benefits outweigh the risks.

Examples of regulatory options to reduce and manage risks include the following:

  • Clinical studies (pre- or postmarket) to further characterize safety, effectiveness, or dose response;
  • Additional product quality information;
  • Postmarket observational studies
  • Enhanced pharmacovigilance;
  • Labeling content (e.g., limitations of use);
  • Risk evaluation and mitigation strategies (REMS).


BRA Lifecycle Approach / Periodic Benefit-Risk Evaluation Reports

The U.S. Authority views BRA as a life-cycle approach. In fact, it recognizes that knowledge of the risks and benefits of a product changes over time as new information about the safety and efficacy of that product becomes available.

According to FDA, sponsors find it useful to have a structured approach to producing the evaluations of new information, as well as the decisions made based on that new information.

In addition, the ICH E2C(R2) guideline recommends, although optionally, developing a Periodic Benefit-Risk Evaluation Report (PBRER).

In any case, sponsors should not wait for a periodic safety update to report a potentially serious safety concern. Any New information about a potential serious safety concern that could have an impact on a drug’s benefit-risk profile should be communicated promptly to FDA.

FDA Guidance Document “Benefit-Risk Assessment for New Drug and Biological Products