Certainty vs. speed: How do patients feel about the tradeoff for new cancer drugs?

A recent study offers insights to an under-examined question at the heart of the FDA’s accelerated approval process.

By Terra Wonsettler, PharmD, MBA

Earlier this year, I wrote in Evidence-Based Oncology about the challenges surrounding drugs using the FDA’s accelerated approval pathway. These therapies first enter the market based on promising early results in clinical trials, yet we often wait years to find out whether they deliver on that promise for the most meaningful endpoints, such as extending survival.

Sometimes, they are true breakthroughs, and the fast-track process saves many additional lives. But often, that is not the case. According to research presented at the American Association for Cancer Research 2024 annual meeting and subsequently published in JAMA, among 46 oncology indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds were converted to regular approval, even though fewer than half of the cancer drugs led to patients living longer, having improved quality of life, or both in confirmatory trials.

Navigating this period of uncertainty poses a challenge for providers, health plans, and patients — though it’s likely many patients are not fully educated on the implications of taking a yet-unproven drug. And if patients had more information, how would they weigh the tradeoffs between getting faster access to a new therapy and accepting some level of uncertainty about the drug’s life-extending benefits?

A fascinating study was recently published in The Lancet Oncology that sheds light on this question. Researchers asked nearly 900 Americans, who had experience with cancer themselves or with family or friends, to choose between two hypothetical drugs being investigated in clinical trials. For each scenario, the drugs differed by the level of certainty that they would increase survival, their effect on a surrogate measure (progression-free survival), and the wait time before FDA approval would make them available. For each scenario, respondents were also asked to imagine themselves having a certain life expectancy or functional status (how well they can carry out daily activities and take care of themselves.)

Among the findings:

• Respondents were willing to wait longer for a higher certainty of benefit. For example, they would wait around 16 months for moderate certainty and about 8 months for low certainty of an additional survival benefit.
• People put relatively little stock in the surrogate outcomes that are typically used to win accelerated approvals. Even when a drug had a substantial benefit for progression-free survival, it did not make up for low certainty that a drug would help people live longer.
• Unsurprisingly, life expectancy and functional status influence preferences. For example, respondents with worse prognoses were more willing to select drugs with low certainty of benefit and less willing to wait for FDA approval.

While these findings were based on hypothetical scenarios, they can reinforce real-world deliberations over these drugs. Where should the FDA strike the balance between speed to market and certainty of benefit? These findings will hopefully spark discussion, spur additional research on this topic, and begin to challenge assumptions about patient preferences. When considering drugs approved by the accelerated approval pathway for patients, physicians need to engage in shared decision making clearly spelling out the uncertainty of benefit.

About the Author

Terra Wonsettler, PharmD., MBA, is Evolent’s vice president of clinical evidence, policy and oncology pharmacy.  Prior to joining Evolent, Dr. Wonsettler started her career as an oncology hospital pharmacist before serving over a decade leading health plan medical and pharmacy benefit administration. She serves on the board of directors for the OH-KY Academy of Managed Care Pharmacy.