The FDA recently issued a final Guidance titled, “Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications.” The purpose of the Guidance is “to provide greater clarity for FDA reviewers and industry regarding the principal factors FDA considers when making benefit-risk determinations during the premarket review process for certain medical devices.” The Guidance applies to diagnostic and therapeutic devices undergoing premarket approval (PMA) or de novo classification; that is, it does not apply to the 510(k) process for determining “substantial equivalence” to an existing and lawfully marketed device.

Section 513(a) of the Federal Food, Drug & Cosmetic Act requires the FDA to determine whether PMA applications provide a “reasonable assurance of safety and effectiveness” by “weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use,” among other relevant factors. This Guidance summarizes the factors the FDA considers when making the risk-benefit determination and also contains several hypothetical examples to illustrate the process. Appendices to the Guidance include the worksheet the FDA uses during the review to summarize its analysis and sample worksheets based on the hypothetical examples. The Guidance, including the examples, seeks “to improve the predictability, consistency, and transparency of the review process for applicable devices” “[b]y providing greater clarity about FDA’s decision-making process.”

The Guidance identifies the following factors the FDA considers when assessing the extent of the probable benefit(s) offered by a device:

• The type of benefit(s)
• The magnitude of the benefit(s)
• The probability a patient will experience the benefit(s)
• The duration of the benefit(s)

To assess the extent of the probable risks, the FDA considers the following factors:

• Severity, types, number and rates of harmful events associated with the use of the device, including:
  • Device-related serious adverse events
  • Device-related non-serious adverse events
  • Complications from procedures
  • Probability of a harmful event
  • Duration of a harmful event
  • Risk of false-positive or false-negative results for diagnostics

The Guidance also mentions the following additional factors that the FDA takes into account in this process:

• The degree of certainty of the benefits and risks of a device
• Characterization of the disease
• Patient tolerance for risk and perspective on benefit
• Availability of alternative treatments or diagnostics
• Risk mitigation
• Post-market data
• Novel technology addressing unmet medical need

Each of the risk, benefit, and additional factors is accompanied by additional explanation. The Guidance also includes discussion of the types of scientific evidence FDA will accept when weighting these factors.

Those interested in more details are advised to consult the Guidance, a pdf copy of which is available here.