Delayed FDA studies leave safety questions unanswered

A safety study required when the FDA approved the autoimmune-disease drug Tavneos in 2021 remains far behind schedule, according to KFF Health News. By last fall, only 21 of the 300 intended participants had joined the study, even as the agency identified dozens of reports of liver damage that it considered possibly or probably linked to the medicine.

The case highlights a broader weakness in the FDA’s system for allowing products onto the market while requiring manufacturers to answer remaining safety or effectiveness questions afterward. An analysis of FDA data by KFF Health News found nearly 600 delayed postmarket studies covering almost 350 products. Some had fallen behind by more than 10 years, while others were still awaiting a workable research plan.

Approval can come before all the answers

Tavneos, made by Amgen, was approved for rare autoimmune conditions despite concerns raised by agency experts during the review. FDA records cited limited safety information, and the approval came with a requirement for a longer-term study after the drug entered ordinary medical use.

That approach reflects a trade-off. Moving a treatment forward can help patients who have severe illnesses and few alternatives. Evidence collected before approval may also fail to show problems that emerge only after a product is used by a much larger and more varied population over a longer period.

The risk is that the follow-up evidence may not arrive promptly. Patients and clinicians can then be left without a clear picture of a product’s benefits and dangers, while insurers, employers and public programs may continue paying for treatments whose value remains uncertain.

Cardiologist Sanket Dhruva, a University of California-San Francisco associate professor who has studied postmarket research, said these requirements have frequently lacked practical force. Harvard Medical School professor Aaron Kesselheim, who has also examined the system, said reducing testing before approval would place greater demands on studies conducted afterward.

The Department of Health and Human Services, which oversees the FDA, said delays can have legitimate explanations and must be assessed individually. Spokesperson Emily Hilliard cautioned that a late study alone does not establish that a product has an unresolved safety or effectiveness problem.

Amgen spokesperson Alison Chartan said the company continues to work on the Tavneos research and remains committed to finishing it.

Delays affect drugs, implants and other products

FDA records examined by KFF Health News include studies involving medicines, biologic products such as vaccines and gene therapies, and medical devices. Postmarket work may take the form of a clinical trial or an analysis of patient data, and a single product may be covered by several studies.

Among the device examples is the CustomFlex Artificial Iris, an implant used to replace an iris that is damaged, defective or absent from birth. A study protocol accepted in 2019 was supposed to follow children for five years. An FDA page downloaded in August showed no enrolled participants. Barbara Fant of Clinical Research Consultants said the rarity of aniridia makes recruitment difficult and that the companies and research group are discussing other ways to meet the FDA’s requirements. She said long-term safety remains a priority.

A study of Pfizer’s covid treatment Paxlovid in pregnant women was supposed to be completed by the end of 2024. FDA records say its completion and final-report deadlines were missed. Pfizer said it was working with the agency and intended to submit its findings as soon as practicable.

The Scandinavian Total Ankle Replacement system also has a long-running study that did not reach its planned scale. The trial, approved in 2009, was meant to enroll at least 500 people but included 142. FDA data showed that nearly half experienced one or more adverse events, including cases involving reoperations, revisions or removals. Representatives for current and former marketers did not answer KFF Health News inquiries.

Another example is Oxaydo, an oxycodone product originally called Oxecta and promoted as intended to deter abuse. The FDA required research into whether it reduced misuse, abuse, overdose, death and addiction, with a final report initially due in 2016. The agency recorded a failure-to-respond letter in 2022. Ownership changed several times, and Acura Pharmaceuticals said in a 2023 filing that it would not continue marketing the product as its patents began expiring. FDA records now list Oxaydo as discontinued.

A larger burden may fall on follow-up research

The FDA database reviewed by KFF Health News listed more than 250 studies whose original final-report deadlines came before July 31, 2026. The agency has sometimes approved extensions and sometimes rejected them; in a small number of cases, the product was withdrawn before the research finished. Its definition of “delayed” covers studies that are overdue or no longer following their original schedule.

Medical-device databases reviewed in August also contained dozens of studies marked as behind schedule. The findings matter because postmarket evidence informs prescribing, patient decisions and spending long after regulatory approval.

The stakes could rise under policy changes intended to speed drug reviews. In February, FDA leaders announced that one clinical trial, rather than two, would become the default basis for approval. Agency officials argued that the shift could lower manufacturers’ costs and bring medicines to patients faster, while saying it would not undermine safety or effectiveness. They also maintained that multiple studies can still produce mistaken conclusions.

Researchers say that if less evidence is collected before approval, the agency must be especially effective at compelling and completing follow-up work. Without that, faster access may come with a longer period in which patients and doctors must make decisions amid incomplete information.