The FDA released draft guidance Aug. 15 aimed at clarifying how benefit-risk determinations are made during premarket review of certain medical devices. The administration is accepting comments on the draft until Nov. 14.

The agency uses safety and effectiveness data in reviewing premarket approval applications (PMAs) and making determinations. Safety data address risk, while effectiveness data address benefit. Reviewers weigh the data to determine whether likely benefits outweigh risks, according to the guidance.

During the decision-making process, medical device reviewers consider types, magnitude and probability of benefits, as well as duration of effects, the FDA stated. Risk factors considered include the number, severity and types of harmful events, as well as probability and duration of harmful events.

“Clinical data [are] the foundation for determining the safety and effectiveness of medical devices requiring FDA premarket approval,” said Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health. “As medical devices grow increasingly complex, many factors impact our benefit-risk determinations, especially for PMA devices. This guidance aims to provide more clarity to manufacturers about what factors we consider when making an approval decision.”

In a hypothetical example portrayed in the draft guidance, the FDA considers an implantable device developed to treat a severe condition.

“There are alternative treatments available for the condition, but they are only effective for certain subgroups of patients and all of them pose significant risks,” the guidance noted. The results of a trial in the fictitious example indicate that potential for a patient to experience substantial benefit is only about 15 percent. But, for the patients who responded, symptoms were significantly reduced and quality of life improved. The duration of benefit, however, cannot be determined because patients were only monitored for a year. There was a low occurrence of harmful events after implantation, but it required a surgical procedure with significant risks. The FDA noted additional factors—uncertainty, patient tolerance for risk, risk mitigation—in the example, as well as the approval or non-approval considerations.

“The device effectiveness is limited because the probability that a patient will experience a benefit is low (15 percent). In this case, [the] FDA does not have the option to limit the use of the device to only those patients who are most likely to experience a benefit because there is no way to determine the subset of patients who would definitely experience the benefit,” the guidance stated.

“Moreover, this type of permanent implantable device poses significant risks and there is moderate uncertainty associated with the trial results,” the agency indicated. “However, for those patients who do experience a benefit, symptom relief and improvement in quality of life is impressive and the risks, although substantial, could be somewhat mitigated through limiting the device use to specialized surgeons. Finally, the device treats a severe and chronic disease for which there are few, if any, alternative treatments. Therefore, [the] FDA is likely to approve the device.”

The FDA noted other examples in the draft, and also proposed a worksheet for medical device reviewers to document how they make determinations. The full guidance can be found here.