Putting Guardrails on Accelerated Approval

The FDA’s controversial approval of Aduhelm (aducanumab) has put a spotlight on the accelerated approval pathway that the agency used to approve the drug. Devised in the early 1990s to make AIDS treatment drugs available more quickly, accelerated approval has become increasingly common, especially for drugs that treat cancer. The pathway has allowed drugs of questionable clinical value to get on the market, its critics say. Proponents, which include drugmakers, some patient groups and many physicians, say it has worked by and large as intended, speeding up access to needed therapies and spurring drug discovery in the process.

In an opinion piece published in JAMA Internal Medicine in July, three experts on drug approvals and costs outlined plans for reforming the accelerated approval process. One of the authors, Aaron Kesselheim, M.D., J.D., M.P.H., voted against approving Aduhelm as a member of an FDA advisory committee and resigned from the committee after the FDA approved the drug.

Kesselheim, a professor at Harvard Medical School; Bishal Gyawali, M.D., Ph.D., an associate professor at Queen’s University in Kingston, Ontario; and Joseph Ross, M.D., M.H.S., a professor at Yale School of Medicine, believe that the use of surrogate markers — usually a lab value or an imaging test result — instead of clinical end points is one of accelerated approval’s problem areas. They say the use of surrogate markers should be curtailed and that confirmatory trials should have clinical end points. Protocols for those confirmatory trials should be finalized as a condition for accelerated approval, they argue, and if a drug fails in a confirmatory trial, withdrawal of the approval that the FDA gave on an accelerated basis should be automatic.

Kesselheim, Gyawali and Ross also believe that the FDA, drugmakers and patient groups should start a public education campaign so patients know that the evidence for drugs approved on an accelerated basis is less certain and that the agency’s OK might be revoked if confirmatory trial results are negative.

Another one of their ideas: CMS and the Department of Veterans Affairs should use their power as payers to rein in spending on drugs that are on the market by virtue of accelerated approval’s lower thresholds. They could limit the prices they pay or exclude the drugs from mandated coverage.