Use of Surrogate Endpoints for FDA Approval is Common in Cancer Drugs             
[Thursday, June 4, 2020]

About 2 out of 3 cancer drug approvals between 1992 and 2019 were based on surrogate endpoints and about 1 out of 3 surrogate endpoints were used first-time for market approval. A recent survey challenges the wide use of surrogate endpoints over direct measures such as overall survival. The authors found that about half of the cancer drug applications that were based on surrogate endpoints such as change in biomarker level or tumor size on imaging studies received accelerated approval, even though there was weak correlation between the surrogate endpoint and overall survival. The surveyors found that of the surrogate endpoints used first time, only about 5% had a strong correlation with overall survival while almost 70% had no or week correlation. The authors present a case for why the first time used surrogate endpoints should be reviewed more critically for correlation with overall survival prior to approval since the post-market studies, that usually used to justify such approvals, are rarely adequate. Since FDA approvals are perpetual, once approved, a new drug quickly becomes widely used based on the marketing efforts by the manufacturer, despite at best weak benefit to the patients. While the authors present a reasonable challenge to the well-established regulatory practice of cancer drug approvals based on surrogate endpoints, these endpoints are popular both with the industry and regulators since they reduce the time to market and the risk of rejection of a product. FDA does encourage sponsors to correlate surrogate endpoints to overall survival but with an extreme public pressure to approval more drugs for treating cancers, it has taken an approach to reduce the burden of approval and let the markets and practice of medicine decide how drugs are used in the real world. Perhaps that is a more pragmatic way. Clinical trials are anyway only a partial presentation of how a product is expected to behave in the real world. The true test of a drug is when it is offered as an option to patients in the real world as that’s where it could make the difference between life and death.