Many Fast-Tracked Drugs Fail to Offer High Added Therapeutic Value, Study Finds

Researchers of a recent study evaluated the therapeutic value of new drugs granted either accelerated approval or conditional marketing authorization compared with drugs already available on the market.

Researchers at Harvard’s Program On Regulation, Therapeutics, and Law recently revealed that most new drug indications granted accelerated approval in the United States or conditional marketing authorization in the European Union (EU) do not appear to add high therapeutic value.

Their study,¹ published August 19 in JAMA Health Forum, looked at the past 15 years (2007 to 2021) and 146 drug indications in the United States and 58 in the European Union. Ratings were available for 90 indications in the United States and 56 in the EU. According to the findings, 39% of those granted accelerated approval and 38% of those given conditional marketing authorization were deemed to offer high therapeutic value at the time of approval. 

In other words, many of the drugs cleared using these fast-track pathways were not found to offer significant advantages over treatments already available.

The study relied on ratings from Canada’s Human Drug Advisory Panel, France’s National Authority for Health, and Germany’s Federal Joint Committee—all national health authorities that evaluate the added therapeutic value of new indications in relation to existing options.

Their assessments “serve as a basis for price negotiations and reimbursement in those countries,” lead author Kerstin Vokinger, MD, JD, PhD, LLM, and colleagues noted, and the value scores they assign “may help guide physicians and patients in treatment selection.”

In some cases, the low ratings could pertain to “the uncertain nature of the data supporting the drugs approved through these pathways,” the researchers explained. 

Previous findings have revealed “the inherently limited and uncertain evidentiary basis on which many drugs are granted accelerated approval and conditional marketing authorization, with questions about the validity of the surrogate measures and biomarkers used to support such approvals,” researchers wrote.

Jodi Segal, MD, MPH, a professor of medicine, epidemiology, and health policy and management at Johns Hopkins University (who was not involved in the study), sees the new findings from a different vantage point. 

In the United States, drugs are not granted approval based on their value as it relates to existing therapeutics, she told First Report Managed Care, and comparative effectiveness isn’t typically considered when drug sponsors submit a New Drug Application. 

“The authors seem disappointed with the number of approved products that are rated as high-value,” added Dr Segal, who also codirects the Center for Drug Safety and Effectiveness at Johns Hopkins, “I was not.” She reasoned that the FDA approves products based on effectiveness and safety, whereas payers determine whether there is enough value to warrant coverage. 

Dr Segal disclosed that she has handled limited consulting for industry within the past year and has a contract with the Centers for Medicare & Medicaid Services on a topic related to drug coverage.

The Accelerated Approval Program² emerged decades ago to help speed the approval of medications that appear promising and fill an unmet need based upon a surrogate endpoint—a marker thought to predict clinical benefit. Drug companies must still carry out studies to confirm that anticipated benefit. This pathway is used to introduce new therapies and to approve additional indications. A notable upside of the program is that it aims to fill a gap for patients, providing quicker access to treatments for severe and potentially life-threatening illnesses.

But critics have pointed out that the trials required to confirm the benefit are sometimes delayed, and some of the drugs are eventually proven to be unsafe or ineffective after they have been available on the market. Beyond that, these therapies tend to carry a hefty price tag during a stretch of time when the evidence regarding patient benefit is still lacking. A July 14 Commonwealth Fund explainer³ highlights controversies surrounding the Accelerated Approval Program as well as solutions that have been proposed, including those geared toward insurance coverage, reimbursement, and cost.

For instance, state Medicaid officials have weighed their options for tackling fast-tracked drug prices. The state of Oregon asked for permission to exclude coverage of these drugs when they lack proof of clinical efficacy—a tactic that could encourage the prompt completion of confirmatory studies. The Institute for Clinical and Economic Review has also suggested “tying coverage to patient benefit and the presence of an outcomes-based contract,” the explainer noted, or creating a safety only pathway that wouldn’t require insurers to pay for approved therapeutics.

Similarly, a Health Affairs paper⁴ published last year put forth recommendations to improve the program, including ideas for pricing and payment reform. In it, Vanderbilt University’s Stacie Dusetzina, PhD, and Aetion’s Nirosha Lederer, PhD, suggested the use of pricing accelerated approval drugs to reflect their value at the time of approval, using indication-based pricing, linking reimbursement to confirmatory evidence, and implementing value-based payment arrangements.

“These proposed changes could better align incentives for drug manufacturers to ensure timely completion of confirmatory trials and could be an opportunity to engage in value-based pricing and payment in an area of potential high costs and high uncertainty of benefit,” they wrote.

Dr Vokinger and colleagues indicated that their findings highlight the need for efficiently carrying out confirmatory studies and making sure these studies are testing “clinically meaningful end points.” In addition, they indicated that their results support efforts currently underway to alter and improve the accelerated pathway. 

The Food and Drug Amendments of 2022, passed by the House of Representatives earlier this year, would enable the FDA to require the start of confirmatory studies prior to accelerated approval, the establishment of enrollment targets, and the reporting of study progress on a biannual basis. Furthermore, they noted, it would codify a streamlined withdrawal procedure that could kick in for a variety of reasons. 

The JAMA Health Forum study received support from the Kaiser Permanente Institute for Health Policy, Swiss Cancer Research Foundation, and Swiss National Science Foundation. In addition, Arnold Ventures supported one of the co-authors