On September 25, 2018, FDA issued a final guidance document: Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different Technological Characteristics (“guidance”). A draft of the guidance was issued on July 25, 2014. When reviewing device 510(k)s, FDA’s review of substantial equivalence first asks whether the new device and predicate device have the same intended use. FDA will next look at whether there are technological differences, and if so, will evaluate if those differences raise different questions of safety or effectiveness. If there are not different questions of safety or effectiveness, FDA will then review test methods and data to determine if the data demonstrate substantial equivalence. The new guidance addresses this last step in the review process where FDA determines if the new device is as safe and effective as the predicate device.
The guidance states “the benefit-risk profile of a new device does not need to be identical to be as safe and effective as the predicate device” and discusses scenarios where a device with a different benefit-risk profile may be considered substantially equivalent (SE). Guidance at 10. The guidance further describes the types of submissions where FDA would recommend sponsors include a benefit-risk assessment within the 510(k). For devices where the benefit-risk profile includes an increased or equivalent benefit with a decreased or equivalent risk, “FDA will generally determine the device SE” and a benefit-risk assessment in the 510(k) will not be needed. Id. at 12. If the new device has increased risk with a decrease in benefit, the guidance states that “FDA will generally determine the device NSE [not substantially equivalent] to the predicate device” and conducting a detailed risk-benefit analysis would also not be warranted. Id. at 12. For situations where there is an increase in risk with an increase or equivalent benefit or a decrease or equivalent risk with a decrease in benefit, including a benefit-risk assessment within the 510(k) is warranted.
The guidance states that FDA will take up to 60 days to operationalize the process and will not request benefit-risk information within that period. Sponsors should plan to include benefit-risk information in future applications or to provide upon request during review. While specific guidance on how to document the benefit-risk assessment is not provided, a number of criteria for performing the evaluation are discussed. In considering a device’s benefit, attention should be given to the:
- magnitude of the benefit,
- probability of the patient experiencing one or more benefits, and the
- duration of the beneficial effect.
For assessing risk, the analysis should consider the:
- severity, type, number, and rates of harmful events,
- probability of a harmful event,
- probability of the patient experiencing one or more harmful events,
- duration of harmful events, and
- risk from false-positive or false negative results for diagnostic devices.
Finally, a benefit-risk assessment should consider additional factors, including uncertainty, characterization of the disease or condition, the use of innovative technology, patient tolerance for risk and their perspective on benefit, benefits for the health-care professional, patient or caregiver, risk mitigation and postmarket data.
The guidance concludes with several examples that should be helpful to sponsors in preparing and documenting the benefit-risk assessment for 510(k) submissions. The guidance is intended to “improve the predictability, consistency, and transparency of the 510(k) premarket review process” and appears that it should provide these benefits. Id. at 4.