Few regulatory tools in modern medicine have drawn as much praise and criticism as the FDA's accelerated approval pathway. Created in 1992 during the AIDS crisis, the program allows drugs for serious conditions to reach patients based on a surrogate endpoint - a laboratory measurement, imaging result, or other marker considered reasonably likely to predict a real clinical benefit - without waiting years for survival or symptom data.
For someone facing a life-threatening illness, those years matter. But approving a drug earlier also means accepting some uncertainty about how well its initial results will translate into meaningful patient benefits.
That tension is built into the pathway. It's also familiar in newer approaches, such as clinical trial protocols that can adapt as a study progresses, where researchers try to move efficiently without weakening the evidence they ultimately need.
Accelerated approval makes a similar trade. The FDA allows a drug onto the market sooner, expecting confirmatory trials to answer the remaining questions. The system's success therefore depends heavily on what happens after approval.
Why Accelerated Approval Can Make Sense
The strongest case for accelerated approval is easy to understand when time itself is part of the problem.
Roughly 80 percent of accelerated approvals have gone to cancer therapies. In oncology, waiting for overall survival data can take years, and patients with advanced disease may not have years to wait. Measures such as tumor response or progression-free survival can provide useful information much sooner.
When a surrogate endpoint has been shown to reliably predict a meaningful clinical outcome, using it isn't simply a way to avoid collecting stronger evidence. It can allow regulators to make a reasonable decision earlier, while confirmatory research continues.
This pathway can be especially important for rare diseases. When only a few thousand people worldwide have a condition, recruiting enough patients for a conventional trial built around a long-term clinical endpoint may be extremely difficult. Accelerated approval can give drug developers another viable route while giving patients access to treatments that might otherwise take much longer to reach them, if they're developed at all.
The conditional nature of the approval also gives the FDA continued authority after a drug reaches the market. The agency can require confirmatory studies, monitor their progress, and ultimately withdraw an approval when the evidence doesn't support the original decision.
The effectiveness of that system, however, depends on how quickly those later steps happen.
Where Problems Begin to Appear
The more difficult record of accelerated approval comes after drugs reach patients.
Among drug-and-indication pairs granted accelerated approval between 2013 and 2023, only about 37 percent converted to regular approval based on confirmatory evidence. In oncology, roughly 23 percent of accelerated approvals were eventually withdrawn after the therapy failed to outperform the standard of care.
Recent FDA tallies also show that 104 of 278 accelerated approval products had incomplete confirmatory trials. For approvals between 2013 and 2017, the average time from approval to completion of those studies increased from 3.4 years to 4.5 years.
Those aren't insignificant delays. During that period, a drug can become part of routine clinical practice, be prescribed to thousands of patients, and generate substantial spending before the original assumptions behind its approval have been fully tested.
Medicare and Medicaid, for example, spent an estimated $18 billion between 2018 and 2021 on drugs with overdue confirmatory trials.
Makena became one of the most prominent examples. The drug was approved in 2011 to reduce the risk of preterm birth. Its confirmatory study failed to verify the expected benefit in an analysis available by 2019, but the FDA didn't formally withdraw the drug until 2023.
That four-year gap illustrates a central concern about accelerated approval. Getting a drug to patients quickly may be justified by the circumstances that led to its approval. Leaving it on the market for years after the supporting evidence weakens is much harder to defend.
The effects can continue even after withdrawal. More than a third of withdrawn indications have remained in national treatment guidelines after their removal, creating another delay between the evidence changing and clinical practice catching up.
Where Reed Seward Sees the Bigger Problem
It's easy to look at those examples and conclude that the FDA simply needs to be more cautious about granting accelerated approval.
But that doesn't address one of the pathway's more persistent problems: confirmatory trials become harder to complete once the drug is already available.
If a study hasn't begun enrolling patients before a drug reaches pharmacy shelves, researchers may suddenly have to recruit participants into a trial involving a treatment they can already obtain outside the study. Sponsors also have less commercial incentive to move quickly on research that could undermine an already-approved product.
In other words, initial approval can make the next stage harder.
That issue has become an important part of the broader debate around the pathway. For Reed Seward and others examining pharmaceutical regulation, the credibility of accelerated approval depends on making the "conditional" part meaningful.
Surrogate endpoints can provide useful early evidence. But if confirmatory research takes many years to establish whether that early signal translated into a meaningful benefit for patients, the system hasn't completed the job it was designed to do.
How the Accelerated Approval Pathway Is Changing
Recent reforms have focused heavily on what happens after approval.
The Food and Drug Omnibus Reform Act of 2022 gave the FDA greater authority to require confirmatory trials to be underway before or shortly after accelerated approval. It also established progress reporting every 180 days and created a more streamlined process for withdrawing approvals when confirmatory evidence fails to support them.
The FDA used that expedited withdrawal authority for the first time in 2024.
Subsequent draft guidance has also clarified what it means for a confirmatory trial to be "underway." Enrollment needs to have started, the expected completion date must reflect diligent progress, and the sponsor's performance should provide reasonable assurance that the study will be completed on time.
Promotional materials have also received additional attention. If a therapy's clinical benefit hasn't been fully verified, how it's presented to physicians and patients shouldn't imply a level of certainty the evidence doesn't support.
Rare diseases still require some flexibility. Recruiting patients for a condition affecting a very small population can take longer for reasons that have little to do with sponsor diligence, so any workable system has to account for those practical limitations.
Other proposals go further. A 2026 white paper from the Institute for Clinical and Economic Review recommended distinguishing more clearly between reliable and less reliable surrogate endpoints, standardizing the FDA's explanations for accelerated approval decisions, informing patients when a drug remains in confirmatory testing, and connecting reimbursement more closely to the strength of the available evidence.
The pricing question is particularly interesting because it gets at the pathway's incentives. If the evidence supporting a drug remains provisional, its price could reflect that uncertainty and change as stronger evidence becomes available.
The Pathway Doesn't Need a Simple Verdict
Accelerated approval has helped therapies reach seriously ill patients years earlier than a conventional approval process might have. It has also allowed some drugs to remain widely available long after questions emerged about whether they delivered the benefits patients were expecting.
Any useful assessment of the program has to account for both parts of that record.
The distinction often comes down to what happens after the initial decision. If confirmatory trials begin promptly, produce reliable evidence, and lead to action when that evidence doesn't support the drug, accelerated approval can do what it was created to do: give patients earlier access while continuing to test whether the treatment delivers meaningful clinical benefits.
Problems arise when the temporary uncertainty built into the pathway becomes open-ended.
The reforms introduced over the past several years are intended to shorten that period and clarify the consequences of failed confirmatory studies. Their effectiveness will ultimately be visible in what happens when the next drug fails to verify its expected benefit: how quickly the evidence is recognized, how clearly patients and clinicians are informed, and how long the drug remains on the market afterward.
About Reed Seward
Reed Seward writes about drug development, clinical trial methodology, pharmaceutical regulation, and the decisions that determine how quickly new therapies reach patients. His work examines the practical tension between giving patients earlier access to promising treatments and ensuring the evidence supporting those treatments holds up as more data becomes available.
His commentary also explores how trial design is changing, including the use of adaptive approaches and surrogate endpoints, and how those decisions affect patients, clinicians, researchers, and health systems once a therapy moves beyond the clinical trial.
Seward shares longer commentary on pharmaceutical regulation and drug development, along with research notes and observations on clinical trials and healthcare. Across that work, the recurring question is practical: how can the drug development process move quickly when patients need it to, without letting early evidence substitute for the stronger evidence that still needs to follow?
