Current standards of drug regulation are insufficient and should be improved for better outcomes

We argue that regulators should take a more selective use of surrogate endpoints when evaluating new drugs.
- Dr Huseyin Naci
Drugs 747x420

A growing number of drugs are being approved on the basis of “surrogate endpoints”. These are indirect measures that are intended to be used as a substitute for a clinically meaningful endpoint. New research co-led by Dr Huseyin Naci of LSE Health and published in the British Medical Journal (BMJ) raises this as a concern arguing that surrogate endpoints provide no guarantee of clinical benefit and should be used only as a last resort in drug trials.

Using surrogate endpoints to measure whether a new drug works can reduce the duration, cost, and complexity of clinical trials before regulatory assessment and facilitate faster patient access to new therapies. However, the researchers argue, their use can have negative implications – such as making decisions more challenging for health technology assessment bodies, and complicating treatment decisions for patients and clinicians.

Dr Huseyin Naci, Associate Professor of Health Policy at LSE, says: “We argue for that regulators should take a 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.”

The recent proliferation of surrogate endpoints by drug regulating bodies, such as the Federal Drugs Agency (FDA), is partly the result of an increase in the use of expedited regulatory pathways that are aimed at speeding up the development, review, and approval of drugs. Over the past quarter century, lobbying by drug companies has put pressure on policy makers to establish several expedited pathways in Europe and the United States.

However, when new drugs are approved based on surrogate endpoints alone, assessing how well they work in terms of patient relevant clinical outcomes, such as health related quality of life and survival, in the short and long term are fraught with considerable uncertainty, the researchers argue.

For patients and clinicians, surrogate endpoints can complicate treatment decisions. Clinicians and patients may misinterpret drug effects on surrogate endpoints as clinically meaningful improvements. This matters, because drugs approved on the basis of surrogate endpoints may not ultimately influence patient relevant outcomes.

The research acknowledges that although surrogate endpoints are widely used by regulators to expedite the approval of new drugs, most are not reliable predictors of outcomes that matter most to patients. Equally, when using surrogate endpoints is justified, regulators should consider the strength of available evidence on how well surrogates predict clinical benefit.

Raising the bar for using surrogate endpoints in drug regulation and health technology assessment is co-written by Dr Huseyin Naci, Dr Dalia Dawoud, Dr Oriana Ciani, and Professor Sylwia Bujkiewicz, and is accessible here.