September 13th, 2018
Is having more treatment options the same as having better treatment options? This is the question cancer patients and oncologists are facing, as the Food and Drug Administration (FDA) approves more and more cancer drugs, with little evidence that the drugs improve survival or quality of life.
The Accelerated Approval Process – created in 1992 to quickly approve a potentially life-saving HIV/AIDS drug – enables “earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” Rather than prove a drug has a beneficial clinical outcome, such as improved survival or better quality of life, the drugmaker just has to prove that the drug improved a surrogate endpoint – a result that correlates with clinical benefit. After the drug is approved on a conditional basis, drug manufacturers are required to conduct a confirmatory trial showing that the drug actually provides a clinical benefit.
Using surrogate endpoints shortens the time it takes to conduct a clinical trial and bring a drug to market, which some argue is essential for patients whose lives are in imminent danger from disease. The trouble with surrogate endpoints, however, is that they often fall short of predicting real clinical benefit. One study of cancer drugs showed that at least half of accelerated approvals used surrogated endpoints that haven’t been proven to correlate with survival. And often after drugs are approved, the post-approval “confirmatory” trials aren’t even conducted.
The pattern of cancer drug approval has moved toward prioritizing speed over evidence, and many doctors and patients view this as a positive trend. As Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said to the independent science magazine UnDark, “The patients are saying ‘we want to accept the tradeoffs, we’ll accept more uncertainty.’”
But do all patients want to accept more uncertainty in outcomes in exchange for more treatment options? In a recent article in the American Journal of Medicine, resident Dr. Derrick Tao, caregiver and patient advocate Sally Schott, and hematologist-oncologist Dr. Vinay Prasad, argue that this narrative leaves out patients who crave better information over more options:
Too often, patients are portrayed on one side asking for access to untested drugs, while regulators insist on careful clinical trials. Instead, we believe the true narrative is some patients are tolerant of risk and desire less regulatory standards, while other patients actually desire increased knowledge regarding their care. The current system has shifted to make more and more drugs available, but failed patients wanting more informed decisions.
For Schott, caring for her brother with advanced cancer was made more frustrating by the lack of controlled data for the treatments they gave him. “For my brother and me, we wanted more information not just more choices,” she writes. Prasad experiences this frustration from the other end, when talking with patients about their treatment options: “After I explain the evidence base, risks, benefits and alternatives, patients sometimes throw up their hands. ‘Why can’t you just tell me if this drug makes me live longer or feel better?'”
The idea that cancer patients want more options, regardless of their effectiveness, is an incomplete narrative. Moreover, the regulatory status quo harms all cancer patients, because it gives drug companies incentives to work on getting drugs approved quickly rather than ensuring that these drugs are effective and safe. If a drug manufacturer can make millions developing cancer drugs using surrogate endpoints, why would they conduct a trial to measure survival, which takes much longer and is more expensive to conduct?
For the sake of all cancer patients, we should demand that surrogate endpoints need to be validated in trials for drugs seeking accelerated approval and ensure that drugs which are approved via the AAP complete confirmatory trials.