Posted 13 May 2015
By Alexander Gaffney, RAC
US medical device regulators at the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) have unveiled a proposed framework for the collection and use of patient preference information (PPI) in medical device development.
The new draft guidance document, Patient Preference Information –Submission, Review in PMAs, HDE Applications, and De Novo Requests, and Inclusion in Device Labeling, is closely related to CDRH's "Patient Preference Initiative," a program started in 2013 to better integrate patients into the medical device regulatory process.
"The Agency understands that patients and caregivers who live with a disease or condition on a daily basis and utilize devices in their care may have developed their own insights and perspectives on the benefits and risks of devices," FDA observes in its draft guidance document. "FDA believes that patients can and should bring their own experiences to bear in helping the Agency evaluate the benefit-risk profile of certain devices."
That's something which has long resonated with regulators, but the devil, as they say, is in the details. Specifically: How should regulators account for the views of patients when reviewing medical products? Are the voices of some patients indicative of the entire group of patients, or just a portion of them? And how should amounts of risk and benefit be quantified?
While FDA still doesn't have all the answers, its latest guidance starts from a basic premise: Companies should collect patient preference data and submit them along with their medical device applications.
But that, too, raises more questions—questions FDA's guidance sets out to answer. For example, what should the submitted patient preference data look like, and how can companies ensure the data constitutes "valid scientific evidence?”
CDRH expresses a preference for two polling methods: a stated preference method and the revealed-preference method. The former elicits responses by "offering choices to patients," FDA explained, while the latter does so by observing "the actual clinical choices made by patients."
FDA's guidance contains extensive recommendations about the "qualities" it wishes to see in all patient preference studies. For example, the studies should be representative of the general patient population and be large enough to be generalizable. A study should also capture the "heterogeneity of patient's preference," as the benefit-risk tradeoffs of different patients may be considerable. Studies should also express the benefits, harms, uncertainties and risk of the product in question.
FDA's guidance also notes that some devices will benefit from PPI more than others. According to FDA, medical devices expected to benefit include:
- devices with a direct patient interface
- devices intended to yield significant health and appearance benefits
- devices intended to directly affect quality of life
- certain life-saving but high-risk devices
- devices developed to fill an unmet medical need or treat a rare disease or condition
- devices with novel technology
The guidance explains that FDA will take into account patient preference studies during the analysis of a device. The agency is statutorily required to assess whether a device demonstrates a "reasonable assurance of safety and effectiveness." Patient preference information could therefore make a compelling case that a device's efficacy outweighs lingering safety concerns that might otherwise sink its chances of approval.
CDRH's assessment process will be slightly different for Humanitarian Device Exemption (HDE)-cleared devices. FDA's HDE process only assesses a device's safety, with consideration of an (unproven) "probable benefit." Patient preference information would therefore be focused on the probable benefits of the device and its safety profile.
Restrictions and Labeling
As FDA explains later on in its guidance document, patient preference information may save a questionable drug from being rejected, but that isn't going to exempt the drug from postmarketing monitoring obligations or other risk-mitigating measures.
"In some cases where FDA determines a product has reasonable assurances of safety and effectiveness in a subset of patients (e.g., based on disease severity) but the device poses potentially serious or life-threatening risks, FDA may determine that conditions of approval are warranted. Patient preference studies may help FDA identify a subset of patients in whom the benefits outweigh the risks, and the approval would not be for the general population but instead would be limited to the population where FDA determines the benefits outweigh the risks. In such cases, certain conditions of Approval may be appropriate to mitigate risk and facilitate use in patients in whom benefits are expected to outweigh risks."
Notably, patient preference information—even scientifically relevant and valid—may also be included in the product's labeling. "Such information can be helpful to healthcare providers and patients in making healthcare decisions involving difficult benefit-risk tradeoffs or novel treatments," FDA said. This is especially important in products with "complex" benefit-risk tradeoffs, the agency added.
Patient Preference Information –Submission, Review in PMAs, HDE Applications, and De Novo Requests, and Inclusion in Device Labeling