Raising the bar for using surrogate endpoints in drug regulation and health technology assessment

In June 2021, the US Food and Drug Administration granted accelerated approval to aducanumab for treating Alzheimer’s disease based on the drug’s amyloid reducing effects. This was despite evidence from several earlier studies that shrinkage of β-amyloid protein plaques does not predictably delay cognitive impairment.1 The controversial decision has drawn attention to the use of surrogate endpoints—laboratory values, radiographic images, or other physical measures that may serve as indicators of clinical outcomes such as symptom control or mortality—in clinical trials of new drugs.2 In fact, the approval of aducanumab is only the latest example of growing regulatory reliance on surrogate endpoints, even though their use can cause problems for patients, clinicians, drug regulators, and health technology assessment bodies. We argue for more selective use of surrogate endpoints when evaluating new drugs, restricting their use to chronic diseases, especially when collecting data on patient relevant clinical outcomes requires trials with unattainably long follow up.