FDA Issues Draft Guidance on Considering Uncertainty in Device Submissions


Posted September 6, 2018

The Food and Drug Administration (FDA) has issued draft guidance intended to update how the agency approaches acceptable levels of uncertainty when determining the benefits and risks of medical devices during certain premarket submissions.

The draft guidance, Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions, provides a framework for how the FDA may approach uncertainty for premarket approval (PMA), de novo classification, and humanitarian device exemption (HDE) premarket submissions. It also includes several examples on how the agency might weigh benefits and risks depending on the proposed levels of uncertainty, the amount of postmarket data collection available, and the context.

“This guidance recognizes that, to meet FDA’s mission to promote the public health in light of inherent uncertainties involved in the provision of medical care, it is important to acknowledge and appropriately address uncertainty in benefit-risk determinations supporting certain FDA premarket decisions,” the FDA wrote in the guidance document. “This includes considering the applicable patient population’s willingness to accept more uncertainty in a device’s benefits and risks, particularly when there are no acceptable alternatives available.”

In addition, new ways of generating evidence, such as in a clinical setting, makes it “important to continuously refine our understanding of how medical devices are used and perform, and corresponding patient outcomes, within the broader healthcare system, which can inform FDA’s regulatory decision making regarding medical devices,” the agency wrote.

According to the draft guidance, the FDA will consider several factors when determining the appropriate levels of uncertainty in its benefit-risk determinations, depending on the circumstances. These include:

  • The extent of the probable benefits of the device, including the type, magnitude, probability, duration, and frequency of those benefits.
  • The extent of the probable risks of the device, including the severity, type, number, rates, probability, and duration of those risks.
  • The extent of uncertainty regarding the benefit-risk profile of alternative treatments or diagnostics.
  • Patients’ perspective on appropriate uncertainty about the probable benefits and risks of the device, if available.
  • The extent of the public health need.
  • The feasibility of generating extensive clinical evidence premarket based on appropriate considerations.
  • The ability to reduce or resolve remaining uncertainty of a device’s benefit-risk profile postmarket.
  • The likely effectiveness of postmarket mitigations, such as labeling and other tools, to help provide a reasonable assurance of safety and effectiveness of the device, as applicable.
  • The type of decision being made. (e.g., the standards of approval are different for an HDE compared with a PMA application.)
  • The probable benefits of earlier patient access to the device.

Comments on the draft guidance can be submitted via www.regulations.gov until December 5.