FDA Proposes Guidelines to Clarify Benefit-Risk Determinations for Medical Devices

  • By: Staff Editor
  • Date: August 19, 2011

The FDA’s new draft guidelines focus on premarket approval applications (PMAs), the regulatory pathway for high-risk medical devices. The recommendations made in the guidance are, according to the agency, intended to improve the predictability, consistency and transparency of the premarket review process for applicable devices, and should help manufacturers go through the approval process easier.

Device reviewers also may consider whether the device is new or a first-of-a-kind technology as part of the benefit-risk determination, particularly if the device treats a disease that has no other treatment.


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Summary of recommendations


The guidance applies to:

  • Devices subject to premarket approval (PMA) applications
  • In limited cases, devices subject to premarket notification (510(k)) requirements
  • Both diagnostic devices and therapeutic devices

Safety and effectiveness data
When reviewing PMAs, the FDA uses safety data and effectiveness data:

  • The safety data addresses risk, and the manufacturer’s ability to mitigate that risk.
  • The effectiveness data considers benefits, as well as other information, to determine whether the probable benefits outweigh the probable risks associated with use of the device.

Safety and effectiveness data alone may not provide a complete picture of the benefits and risks. FDA medical device reviewers objectively look at other factors such as the severity of the disease the product diagnoses or treats and whether or not alternative tests or treatments are available.

Both clinical and non-clinical data can play a role in the FDA’s benefit-risk determinations.

Factors FDA considers in making benefit-risk determinations

Measures for effectiveness of devices:

The type of benefits
  • The device’s impact on clinical management of the patient,
  • The patient’s physical health
  • Patient satisfaction in the target population, and can range from significantly improving patient management or reducing the probability of death, to aiding in some improvement of management or reducing the probability of loss of function, to providing relief from minor symptoms.
The magnitude of the benefits in the individual patient
  • The magnitude measures the size of the benefit and is often measured along a scale or according to specific endpoints or criteria (types of benefits).
  • The change in the patient’s condition or their clinical management as measured on that scale, or as determined by an improvement or worsening of the endpoint.
The probability of the patient experiencing a benefit
  • Based on the data provided, it is sometimes possible to predict which patients may experience a benefit but sometimes this cannot be well predicted.
  • A benefit may only be experienced by a small portion of patients in the target population, or a benefit may occur frequently in patients throughout the target population.
  • It is also possible that different patient subgroups will experience different benefits or different levels of the same benefit.
The duration of effects
  • Some treatments are curative while some may need to be repeated frequently over the patient’s lifetime.
  • Treatments that are curative may be considered to have greater benefit than treatments that must be repeated because repetition may introduce greater risk or the benefit experienced may diminish each time the treatment is repeated.


Measures for safety of devices

The extent of the probable risk/harm is measured by taking into account the following factors:


Number, severity, and types of harmful events associated with the use of the device
  • Device-related serious adverse events – an injury or illness that is life-threatening, results in permanent impairment or damage to the body, or requires medical or surgical intervention to prevent permanent harm to the body.
  • Device-related non-serious adverse events – those events that result directly from use of the device and that do not meet the criteria for classification as a serious adverse event.
  • Procedure-related or indirect harms – harm to the patient that would not be considered a serious or non-serious adverse event, and that indirectly results from use of the device.
Probability of a harmful event The percent of the intended population that would expect to experience a harmful event.
Duration of harmful events Some devices can cause temporary, minor harm; some devices can cause repeated but reversible harm; and other devices can cause permanent, debilitating injury.
Risk from false-positive or false-negative for diagnostics
  • If a diagnostic device gives a false-positive result, the patient may receive an unnecessary treatment and incur all the risks that accompany that treatment, or may be incorrectly diagnosed with a serious disease.
  • If a diagnostic device gives a false-negative, the patient may not receive an effective treatment and will miss out on the benefits it would confer, or may not be diagnosed with the correct disease or condition.


The agency also considers the number of different types of harmful events that can potentially result from using the device and the severity of their aggregated effect. When multiple harmful events occur at once, they have a greater aggregated effect.

Additional factors for risk/benefit determination


The degree of certainty of the benefits and risks of a device is a factor the FDA considers when making benefit-risk determinations.
Characterization of the disease
  • The treated or diagnosed condition
  • Its clinical manifestation
  • How it affects the patients who have it
  • How and whether a diagnosed condition is treated
  • The condition’s natural history and progression
Patient tolerance for risk Different factors can influence patient risk tolerance, including:
  • Disease severity – patients suffering from very severe diseases may tolerate more risk for devices used in treatment. For diagnostic devices, individuals with severe diseases may be more adverse to the risk of a false negative.
  • Disease chronicity – some patients with chronic diseases who have adapted to their illness and minimized its interference with their daily lives may tolerate less risk and require risky devices to deliver a greater treatment benefit
  • Availability of alternative treatment/diagnostic options – if there are no other treatment/diagnostic options available, patients may tolerate more risk for even a small amount of benefit.
Risk mitigation The use of mitigations such as warning labels can minimize the likelihood of a harmful event occurring.
Novelty of technology Devices representing or incorporating new technologies, especially those that are first-of-a-kind, may provide a less than optimal benefit, but may also offer advantages that did not previously exist.

Benefit/risk worksheet

The guidance proposes that medical device reviewers use a worksheet to document how they make benefit-risk determinations. In certain cases, this document could be made public post-approval, making the FDA’s decision making process even more transparent.

Additional resources

-    Read the draft FDA guidance for benefit risk determination of medical devices in full

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