Study: Patients may not understand evidentiary differences for conditionally approved drugs

A majority of cancer survivors surveyed about a hypothetical drug approved by the US Food and Drug Administration (FDA) through a proposed new pathway for diseases with unmet needs appeared less willing to enroll in a clinical trial when a conditionally approved drug is available, and seemed unaware that conditionally approved drugs would have a lower evidentiary requirement than traditionally approved drugs, according to a recent research letter published in JAMA Network Open.

“This survey study found that a sample disclaimer may not convey lower evidence requirements and reduced certainty of efficacy of conditionally approved drugs, suggesting the need for robust education before consent for treatment with these drugs,” Luke W. Chen, of the American Cancer Society Cancer Action Network, and colleagues wrote in their paper.

In the survey, researchers polled 1,597 patients from the American Cancer Society Cancer Action Network survivor views program about a proposed conditional pathway who were mainly under 65 years of age (53.1%) and had received treatment for cancer within the last 7 years. Most of the group consisted of White (72.5%) women (82.2%) who had breast cancer (54.9%) and who answered the survey between July 2024 and August 2024. Chen and colleagues asked patients to respond to hypothetical scenarios that included enrolling in a clinical trial where there were no effective treatments or there was a conditionally approved drug available, and rate on a 1-7 scale their likelihood of enrollment under each scenario.

The researchers also evaluated patient understanding of the conditional approval pathway by writing out the language included in proposed legislation: “This drug is conditionally approved for use in a limited and specific population. This drug has not received full approval by the Food and Drug Administration. Conditional approval of this drug may be withdrawn at short notice.” Researchers then asked patients to rate on a 1-5 scale whether they believed such a drug conditionally approved under the new pathway had been extensively tested for safety and efficacy in clinical trials, and if they believed the drug was likely or unlikely to control their cancer.

Chen and colleagues found respondents were significantly less likely enroll in a clinical trial when a conditionally approved drug was available compared to when there was no treatment available (P < .001). More than half of patients (55.8%) said they were likely or very likely to enroll in a hypothetical clinical trial if no conditionally approved drug was available, which decreased to more than one-third of patients (37.1%) in the presence of a hypothetical conditionally approved drug. When asked to choose between the drug, a trial, or no treatment, 35.9% of patients said they would pick the conditionally approved drug, 32.4% said they would enroll in the clinical trial, and 3.6% of patients noted they would not seek treatment.

“After FDA accelerated approval of a drug, subsequent required confirmatory trials face challenges in accruing participants. Similarly, we found a significantly reduced likelihood of enrolling in a trial when a conditionally approved drug is available,” Chen and colleagues said.

In terms of safety, 51.6% of respondents said they believed the drug was extensively tested for safety, while 12.6% said they believed it was not extensively tested. Respondents answered similarly for efficacy, with 55.8% believing the drug was extensively tested for efficacy compared to 11.7% believing it was not. Most respondents said they also believed the conditionally approved drug would control their cancer, while a minority thought the drug was unlikely to control their cancer (58.3% vs 9%).

Researchers also asked respondents if they believed patients and insurance companies should pay for conditionally approved drugs. Of those surveyed, 45.8% said patients and insurance companies should not pay, while 34.1% thought they should pay for drugs. When asked if respondents believed if patients and insurance companies should pay for pediatric drugs with a conditional approval that had results of efficacy from animal testing, 54.2% of respondents said patients and insurance companies should not pay for the drugs, and 15.6% said they should pay for the drug.

“Our findings suggest that patients with cancer do not broadly embrace payments for drugs that have not met traditional approval standards,” the researchers said.

Patient, physician education needed

Anjali Deshmukh, MD, JD, associate professor in the Seton Hall Law School, and a board-certified pediatrician, told Focus in an interview that there would be a need for more patient and physician education on the safety and efficacy of conditionally approved drugs under a new proposed pathway.

“Understanding risks of a new treatment is important, but translating technical findings, complex science, and statistics for patients can be challenging. Changes to FDA evidentiary thresholds through new approval pathways and designations can make that task even harder,” Deshmukh said. “In my clinical and legal experience, some patients, families, and even physicians have misperceptions about the quality and quantity of evidence generated before approval. Other recent studies have confirmed that physicians may lack familiarity with drug and medical device regulatory practices and can be under the impression that the data supporting FDA drug and high-risk device approvals are more rigorous than they often are.”

The finding that 45% of surveyed patients were unwilling to pay for conditionally approved drugs is “fascinating—suggesting perhaps that many patients expect drug prices to reflect the demonstrated value they provide,” Deshmukh said.

“For example, it could mean that patients believe higher prices may only be justified for treatments that are proven to be highly effective and safe,” Deshmukh explained. “How much and who should pay for conditionally approved drugs is a deceptively difficult question.”

Deshmukh noted this tension between cost, access, flexibility, and rigor has been raised before in previous research. A recent study in Health Affairs Scholar found that regulators, industry executives, payers, and patient advocates largely agreed on the barriers to timely completion of postmarketing studies for accelerated approval drugs and supported payment reform but disagreed on potential solutions and their implementation.

“Debates over insurance coverage for hepatitis C therapies, as well as the steep costs of cell and gene therapies, highlight how complex these issues have become,” Deshmukh said. “Central questions remain about how to determine a drug’s value, who should bear its cost, and whether, and under what circumstances, access should be limited by price. With AI-driven advances changing the cost of drug discovery, there needs to be a larger conversation on drug value and what it means for a drug to be accessible.”

JAMA Network Open Chen et al.

Study: Patients may not understand evidentiary differences for conditionally approved drugs

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