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Uncertainty as a Factor in Determining Benefit-Risk for Pre-market Approval of Medical Devices


With the recent announcement from FDA’s Center for Devices and Radiological Health (CDRH) about their finalization of guidelines towards accepting a higher premarket uncertainty with regards to the benefit-risks of medical devices, things might change for better.

At times, there is a considerable amount of uncertainty with regards to several aspects surrounding a device and the ways in which it might be of risk or benefit to the patient. This includes the category of the device, its extent, magnitude, frequency and such other things. The statutory benchmark including some marketing authorizations mandates that a “reasonable” assertion is better than complete assertion while judging whether a device is safe or effective.   

The apt extent of improbability regarding a device’s advantages and drawbacks is dependent on the nature of premarket judgment and its background. Thus, the prime uncertainty in a benefit-risk assessment to hold a premarket decision for a device would be based on the context; this would include the entirety of information regarding the device. FDA takes into account a number of factors depending on the context while judging the benefit-risk uncertainty, like:

  • The extent of the probable benefits of the device, taking into account the type, magnitude, probability, duration, and frequency of those benefits, including if the probable benefits are greater or less than those of approved or cleared alternative treatments or diagnostics or the standard of care; 
  • The extent of uncertainty regarding the benefit-risk profile of approved or cleared alternative treatments or diagnostics or the standard of care (e.g., the strength of the evidence supporting the alternative treatment or diagnostic);
  • Patients’ perspective on appropriate uncertainty about the probable benefits and risks of the device, if available;
  • The extent of the public health need (e.g., seriousness of the illness; benefit-risk profile of other available therapeutics or diagnostics, if any, including the current standard of care; the portion of the target population for whom there would be a positive benefit-risk profile); 
  • The feasibility of generating extensive clinical evidence premarket based on appropriate considerations, e.g., taking into account the prevalence of the disease or condition; 
  • The ability to reduce or resolve remaining uncertainty of a device’s benefit-risk profile post-market (e.g., consideration of FDA’s authority to require post-market data collection and the likelihood that the necessary post-market data collection will be completed within reasonable timeframes);
  • The likely effectiveness of 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., there is generally likely to be more uncertainty surrounding a device’s benefit-risk profile based on the evidence submitted in an HDE application, as compared to a PMA, because the standards for approval are different); and 
  • The probable benefits of earlier patient access to the device. 

FDA is supposed to consider these aspects in a practical manner depending on the contextual details like the appropriate clinical and non-clinical details related to the device. These details might include the way the device works and the manner in which they might fail and these are to be in consistence with the requirements of FDA’s statutory and regulatory authority.