The FDA has issued guidance describing in detail how the risks and benefits of a new device should be considered when the device is up for premarket approval or de novo classification.
In its decisionmaking, the FDA will consider the types of benefits, their magnitude, the probability of the patient having one or more benefit and the duration of effects.
It will also consider the extent of the probable risks and harms, including severity, types, device-related adverse events, procedure-related complications, and the number and rates of harmful events associated with the device.
When assessing the probability of a harmful event, the FDA will consider the portion of the intended patient population likely to experience the event, factoring in whether the event occurs once or repeatedly. It will also consider duration and severity, as some adverse events may be reversible while others can cause permanent harm.
“We also consider the number of different types of harmful events that may result from using the device and the severity of their aggregate effect,” the guidance says. “When multiple harmful events occur at once, they have a greater aggregate effect.”
Additional factors the FDA considers include uncertainty, patient-reported outcomes, characterization of the disease, availability of alternatives, risk mitigation, postmarket data and whether the device is a novel technology addressing an unmet need.
One factor specifically related to diagnostics is the risk from false-positive or false-negative results, the guidance says.
It notes that “although a great deal of emphasis” is placed on clinical data, “nonclinical data also can be critical to understanding a device’s safety and effectiveness. Medical devices often have attributes that cannot be tested during clinical methods alone and that play a major role in the safety or effectiveness of the device.”
For example, with some implants, better long-term evidence has come from engineering tests that challenge the device in worst-case conditions and simulate years of use.
The guidance includes a worksheet that reviewers use to make risk-benefit determinations. However, the weighting of factors for a certain device type can change over time, making the weighting different for a similar type of device in the future.
The FDA hopes that by clarifying its decisionmaking process, it can improve predictability, consistency and transparency for sponsors, it says.
Factoring in Patient Preferences
A second FDA guidance outlines how to incorporate patient preference information into the medical device development and approval process.
Sponsors and other stakeholders should meet early with their review division if they are thinking of submitting patient preference information, the guidance advises.
Additionally, “the agency may also consider obtaining its own PPI to further understand the benefit-risk factors affecting patients with diseases or conditions who may be considering using a specific device type,” the guidance says.
It recommends certain qualities for patient preference studies, including patient centeredness; representativeness of the sample and generalizability of results; capturing heterogeneity of patients’ preferences; minimal cognitive bias; robustness of analysis of results; study conduct; and comprehension by study participants.
In some cases, patient preference studies can help the FDA and companies find patient subsets for whom the benefits of a device outweigh the risks, leading to approval in a limited population. In such cases, the agency may require approval conditions such as specialized labeling.
The guidance also gives recommendations on collecting and submitting patient preference information to the agency and discusses the inclusion of that information in decision summaries and device labeling.
For example, whenever possible, “the likelihood of risks and benefits should be expressed in absolute terms rather than relative terms that may be confusing,” it says. “Doubling a risk means very different things if that entails an increase from 10 percent to 20 percent rather than an increase from 0.001 percent to 0.002 percent.”
The risk-benefit guidance is available at . The guidance on patient preference information is available at www.fdanews.com/08-24-16-patientpreferenceguidance.pdf. — April Hollis