Dhruva Details How Physicians Can Learn More About the FDA Approval Process

Sanket Dhruva, MD, MHS

Despite the continued use of expedited approval pathways, which are designed to make novel drugs and high-risk medical devices available to patients more quickly, physicians report a lack of understanding when it comes to the FDA approval process, according to Sanket Dhruva, MD, MHS.

Data published in JAMA revealed that 77% (95% CI, 73%-80%) of physicians (n = 683) thought when the FDA calls a drug a breakthrough, it means high-quality evidence has shown the drug is more effective compared with currently approved treatments.¹

“There’s something naturally about this term breakthrough that makes it more likely that physicians and patients are going to use or recommend use of this [drug or] device, even though the breakthrough designation means that there’s more flexible study designs. It’s particularly important that the connotation of the word breakthrough is affecting patient and physician perceptions,” Dhruva said in an interview with OncLive®.

Additionally, findings from a study published by Dhruva et al demonstrated that among board-certified physicians in internal medicine, medical oncology, or cardiovascular medicine surveyed on drugs (n = 489) and medical devices (n = 479) only 41% of self-reported they understood the FDA approval process extremely well or moderately well for drugs and only 17% for high-risk medical devices. Physicians did not understand the process well at all at rates of 12% for drugs and 39% for devices.²

When asked about their perception of the current bar for FDA approvals for drugs vs medical devices, physicians believed it was too high or much too high (12% vs 8%, respectively), about right (59% vs 66%), or too low/much too low (29% vs 26%). Further, 47% reported they thought that the 5-year changes in the approval threshold have fallen or become more lenient for drugs rather than stayed the same (42%) or risen/become more stringent (11%). Most reported they felt the FDA approval threshold has stayed the same for medical devices (71%).

In the interview, Dhruva, an assistant professor of medicine at the University of California, San Francisco School of Medicine, highlighted how physicians and those in training can learn more about the approval process. He also described the findings from the national physician survey study in an additional interview.

OncLive: What is notable about the use of expedited pathways in the FDA approval process?

Dhruva: The goal of this approval process is to use earlier-stage data to get new devices and drugs to patients more quickly so that they can be used in the diagnosis, treatment, and prevention of disease. In 2012, the breakthrough therapy designation for drugs was written into law via the FDA Safety and Innovation Act of 2012 [and] in the 21st Century Cures Act of 2016, the breakthrough devices program was written into law.

These expedited pathways have been increasingly used in FDA regulatory decision-making, and, in general, these pathways allow for the use of earlier stage data [from] smaller clinical trials, shorter trials, and trials that are focused on surrogate measures, such as laboratory tests or imaging tests, as opposed to clinical end points such as how patients live or feel. This is important and the reasoning behind this is to get drugs and devices to patients more quickly if there is promise, but that needs to then be matched in the post-approval setting [with] information about risks and benefits, and post-approval trials conducted verifying safety and effectiveness.

One important factor about the breakthrough designation is a study has shown that if patients were recommended to get a drug and if it was termed a breakthrough vs without the term breakthrough, they were more likely to want to use the drug and more likely to believe it is effective. Similar analogous research has been conducted with physicians; if you say that a drug is a breakthrough, then physicians believe that it is more effective than it may be.

What can physicians do to learn more about the approval process?

We think that covering these topics in medical education would be important and that this should be a part of medical school so that physicians can understand the basics of medical product approvals and medical product regulation.

We also believe that there should be more tailored education during subspecialty training. For example, oncologists are more commonly using drugs that are approved through the accelerated approval pathway, so it’d be very helpful if during oncology training physicians understood what the accelerated approval program is, what it entails, and what the evidentiary standards are. [It would allow them to] better provide context for their clinical decision-making and for patients when they’re recommending a drug that’s come to market through the accelerated approval program.

For example, cardiologists use a lot of medical devices—cardiovascular devices—in clinical practice such as heart stents, defibrillators, and newer medical devices like leadless pacemakers. Perhaps more information for cardiologists about the FDA regulatory process for medical devices would be helpful [through] more tailored education.

Additionally, the vast majority of physicians are in clinical practice and there’s a role for Continuing Medical Education [CME], when it includes information about drugs and devices, to also describe the evidence that was reviewed by the FDA to support the approval as well as the status of required post-market studies. There is a real need and emphasis on post-market evidence generation and having that in CME could be important.

The ‘Drug Trials Snapshots’ that [are released by the FDA and] provide information about newly approved drugs could be extended to medical devices as well. There are a few different avenues to help improve understanding of drug and medical device regulation for both physicians early in their training as well as those who have already completed their training and are in clinical practice.

How critical is knowledge of the approval process when making decisions for patients?

It’s absolutely critical. FDA authorization is necessary for the use of drugs and medical devices in clinical practice and understanding how regulation occurs, the evidence that was used to support approval, uncertainties, and the limitations—which can include the use of surrogate end points and the lack of blinding—is [key]. We also must counsel patients about all these factors as well as post-market evidence.

It would be very helpful to tell patients that we’re recommending this drug because we think that it’s going to help them while also acknowledging there is uncertainty based on [certain] factors and that there is ongoing post-approval evidence generation. That is very different and can help patients make more informed decisions based on the totality of evidence rather than the absence of that information or simply stating that we have a breakthrough drug that we’re going to recommend. It’s important that patients are provided relevant, meaningful information to be able to inform decisions in their care [and we must] honor the ethical principle of patient autonomy.

Are there any questions you still have on the approval process or any changes that you’d like to see made?

As a physician, I would reflect on the findings of our paper that physicians are generally looking for greater rigor when drugs and devices are coming to the market compared with how often the standards are used to support approvals. They’re looking for greater rigor in the evidentiary standards and are looking for regulatory action when post-approval trials are either not conducted, not conducted meeting timelines, or conducted and show that a drug or device doesn’t work. I would echo what we are hearing from this random national sample of board-certified internists, oncologists, and cardiologists in those domains.

What do you want colleagues to take away from this research?

It’s important to better understand the FDA regulatory processes because this affects the drugs and devices that are ubiquitously used in clinical medicine. It’s very important to have this context to be able to make informed recommendations to patients and adequately counsel patients about benefits and risks.

We are in the process of a follow-up to this work, surveying UCSF health professional students on what they’ve learned about drug and medical device regulation. We’re surveying medical, pharmacy, and dental students here at our local institution. Hopefully, this will help to provide further information and inform strategies to help close these gaps in physician understanding, and depending on what we find, health professional understanding of drug and device regulation.

References

1. Kesselheim AS, Woloshin S, Eddings W, Franklin JM, Ross KM, Schwartz LM. Physicians’ knowledge about FDA approval standards and perceptions of the "breakthrough therapy" designation. JAMA. 2016;315(14):1516-1518. doi:10.1001/jama.2015.16984
2. Dhruva SS, Kesselheim AS, Woloshin S, et al. Physicians’ perspectives on FDA regulation of drugs and medical devices: a national survey. Health Aff (Millwood). 2024;43(1):27-35. doi:10.1377/hlthaff.2023.00466