Expedited Approval of Medications Calls Evidence Standards into Question
Expedited FDA approval processes pose multiple ethical concerns, according to the authors of a recent paper.1 The authors sought to “illustrate the overarching trend in drug approval over the past 60 or so years,” says lead author Jonathan Darrow, SJD, LLM, JD, MBA, faculty member at the Center for Bioethics at Harvard Medical School.
Evidence standards for drug approval, put in place in 1962 by the Kefauver-Harris Amendment, resulted in higher costs and slower availability. “Since then, pressure from industry and patient groups, often funded by industry, have led to a gradual erosion in evidence standards that has continued to the present,” Darrow says.
Darrow believes most newer drugs and devices are not needed in the first place. “They not only have uncertain benefit due to eroding evidence standards, but these drugs are often not meaningfully better than older drugs, based on the evidence we do have,” he says.
With appropriate guidance from well-informed physicians, patients can avoid paying high prices for newer drugs by turning to older, generic drugs. About 90% of prescriptions already are for generic drugs.2 “This number could likely rise higher with more discerning prescribing practices,” Darrow argues. “Better disclosure to patients and clinicians is needed so that expensive new products are not assumed to be better than lower-cost older ones.”
The acceptance of less and weaker evidence for approval “has been a growing trend at FDA,” says Holly Fernandez Lynch, JD, MBe, assistant professor of medical ethics at the University of Pennsylvania. The key is finding the right balance between speed and certainty. “You don’t want patients who could be helped by a drug not to be able to access it because FDA is demanding too much evidence. But you also don’t want patients to be left with a bunch of ineffective or unsafe drugs because FDA isn’t demanding enough evidence,” Fernandez Lynch says.
With expedited FDA approval, “the big concern is that there seems to be tension between access and evidence,” says Alison Bateman-House, PhD, MPH, MA, assistant professor in the division of medical ethics at NYU Grossman School of Medicine.
Patients want quick access to medications that are proven safe and effective. “How expedited can you go before you cross that threshold and have gotten to a point where you are giving access to a drug that is not safe or effective?” Bateman-House asks.
In some cases, approval is retroactively stripped as evidence comes in showing the previously perceived safety and efficacy does not pan out.3 Still, unmet need for treatment for serious or life-threatening diseases spurs pressure to speed the approval process.
“Since we do have regulatory pathways to allow products to be brought to market on relatively little evidence, of course people are going to use them,” Bateman-House says. “But as a society, we need to sit back and say, ‘Are these expedited pathways a net gain or a net loss?’ I don’t think we have a definitive answer to that yet.”
From the perspective of the general public, approved drugs are safe drugs; the quicker the approval process, the better.
“People bought into the ‘access is good’ narrative unhesitatingly,” Bateman-House says. “But not all access is good access, and not all drugs are good drugs, and not all drugs are safe.” For decades, “all the pressure has been toward access. But we are in the middle of a pendulum swing,” Bateman-House adds.
People are starting to see the danger when drugs are approved without enough evidence of safety or efficacy. For drugmakers, one important consequence is health plans might refuse to cover the questionable drug.
“The FDA used to be the gold standard as the gatekeeper. But the FDA is starting to permit the introduction of products to the market that payers are not certain about,” Bateman-House observes.
If the health plans are not convinced the evidence of a medication’s effectiveness is solid, there is nothing stopping the plan from refusing reimbursement.4
“No company wants to bring a product to market, and suddenly payers are refusing to pay for it,” Bateman-House says. “We are now seeing that happen.”
- Darrow JJ, Dhruva SS, Redberg RF. Changing FDA approval standards: Ethical implications for patient consent. J Gen Intern Med 2021;36:3212-3214.
- U.S. Food & Drug Administration. Statement on continued progress enhancing patient access to high-quality, low-cost generic drugs. Oct. 16, 2019.
- Vitry A, Nguyen T, Entwistle V, Roughead E. Regulatory withdrawal of medicines marketed with uncertain benefits: The bevacizumab case study. J Pharm Policy Pract 2015;8:25.
- Kaltenboeck A, Mehlman A, Pearson SD. Strengthening the accelerated approval pathway: An analysis of potential policy reforms and their impact on uncertainty, access, innovation and costs. Institute for Clinical and Economic Review. April 26, 2021.
Patients want quick access to medications that are proven safe and effective. But how fast is too fast?
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