The US Food and Drug Administration (FDA) clearly states that surrogate markers must undergo testing to confirm that they are indeed validated endpoints when used in clinical trials to study a drug's efficacy. The proportion of cancer drugs approvals based on surrogate endpoints, such as objective response rates or progression-free survival, is increasing each year.
Given this, one might assume that the FDA has performed its own research on surrogate markers to justify approval decisions for many cancer drugs. However, that is not necessarily the case. Our research shows that although the FDA published a table of surrogate endpoints that formed the basis for drug approvals, many had limited evidence to support their use. Some surrogates had never been formally tested, whereas others were included despite poor performance as a surrogate endpoint.
This finding piqued my curiosity, and I went on a mission to see how many surrogate validation studies the FDA had conducted. I found only four such studies. And the results did not inspire confidence.
Surrogate Validation Studies to Date
The first explored whether pathologic complete response (pCR) could be used as a surrogate for overall survival in patients with early breast cancerThis 2014 analysis found that although pCR was a prognostic marker in individual patients, it was a very poor surrogate endpoint for overall survival. Reassuringly, the FDA has followed these results and has not approved drugs on the basis of pCR in breast cancer.
The FDA Should Listen to Its Own Evidence on Surrogate Markers
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COMMENTARY
The FDA Should Listen to Its Own Evidence on Surrogate Markers
Bishal Gyawali, MD, PhD
DisclosuresNovember 12, 2021
The US Food and Drug Administration (FDA) clearly states that surrogate markers must undergo testing to confirm that they are indeed validated endpoints when used in clinical trials to study a drug's efficacy. The proportion of cancer drugs approvals based on surrogate endpoints, such as objective response rates or progression-free survival, is increasing each year.
Given this, one might assume that the FDA has performed its own research on surrogate markers to justify approval decisions for many cancer drugs. However, that is not necessarily the case. Our research shows that although the FDA published a table of surrogate endpoints that formed the basis for drug approvals, many had limited evidence to support their use. Some surrogates had never been formally tested, whereas others were included despite poor performance as a surrogate endpoint.
This finding piqued my curiosity, and I went on a mission to see how many surrogate validation studies the FDA had conducted. I found only four such studies. And the results did not inspire confidence.
Surrogate Validation Studies to Date
The first explored whether pathologic complete response (pCR) could be used as a surrogate for overall survival in patients with early breast cancerThis 2014 analysis found that although pCR was a prognostic marker in individual patients, it was a very poor surrogate endpoint for overall survival. Reassuringly, the FDA has followed these results and has not approved drugs on the basis of pCR in breast cancer.
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Lead image: Bishal Gyawali, MD, PhD
Medscape Oncology © 2021 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: The FDA Should Listen to Its Own Evidence on Surrogate Markers - Medscape - Nov 12, 2021.
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Authors and Disclosures
Authors and Disclosures
Author
Bishal Gyawali, MD, PhD
Associate Professor, Department of Oncology, Queen's University, Kingston, Ontario, Canada
Disclosure: Bishal Gyawali, MD, PhD, has reported the following relevant financial relationships:
Received consulting fees from: Vivio Health