FDA Finalizes Guidance On Benefit-Risk Determinations, Patient Preference Information

By Jof Enriquez,
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The U.S. Food and Drug Administration (FDA) has issued final guidance on factors in making benefit-risk determinations for premarket approval (PMA) and de novo classifications, as well as related final guidance on patient preference information to help FDA evaluate the benefit-risk profile of certain devices.

According to the final benefit-risk guidance, FDA evaluates benefits by taking into account the type and magnitude of benefits, the probability of the patient experiencing the benefit(s), and how long any benefit lasts. In assessing risk, FDA looks at the severity, types, number, and rates of harmful events associated with the use of the device, and the probability and duration of harmful events. Risks from false-positive or false-negative results for diagnostics are likewise considered.

Additional factors when making benefit-risk determinations include: the degree of certainty of the benefits and risks of a device, patient-centric assessments and patient-reported outcomes (PROs), the characterization of the treated or diagnosed disease/condition, alternative treatments or diagnostics, novel technology addressing unmet medical needs, risk mitigation, postmarket data, and patient perspectives.

The factors listed are similar to those itemized in draft guidance for assessing benefit-risk in device compliance and enforcement decisions, released in June.

The finalized benefit-risk guidance issued this week includes four hypothetical examples of benefit-risk determinations, as well as appendices on the intersection of the guidance with ISO 14971, a worksheet for benefit-risk determinations and worksheets for the examples, according to RAPS.

Because patients may perceive risks and benefits differently from regulators, manufacturers, care providers, or other patients, FDA believes that their unique input should be considered in decision-making. The agency last September formed the advisory-level Patient Engagement Advisory Committee (PEAC) with the purpose of focusing on patients' perspectives on medical device development and regulation.

For clarity, FDA this week released final guidance for sponsors submitting patient preference information (PPI) that may be used by FDA staff in decision-making related to PMAs, humanitarian device exemption (HDE) applications, and de novo requests.

In the document, FDA defines PPI as "qualitative or quantitative assessments of the relative desirability or acceptability to patients of specified alternatives or choices among outcomes or other attributes that differ among alternative health interventions."

"Evaluations of patient-centered variations in tolerance to risks and perspective on benefits may, in the aggregate, reveal a population-level assessment of patient benefit-risk preference for that device, which may be considered valid scientific evidence (see 21 CFR 860.7) and may inform FDA’s benefit-risk assessment for a device subject to review in a PMA, HDE application, or de novo request," states FDA in the final guidance.

FDA recommends ideal qualities of patient preference studies in support of PMAs, HDE applications, or de novo request submissions. It also recommends that device product labeling contain sufficient information about the benefits and risks of the treatment and diagnostic options under consideration, and should generally contain information that may assist patients in understanding risks and benefits.

The final guidance document also includes an appendix and diagram showing how PPI can be incorporated throughout the total product lifecycle.