[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 598
Citations 0
July 23, 2020

What Constitutes a Valid Surrogate End Point in Cancer Clinical Trials?

Author Affiliations
  • 1Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 3Associate Editor for Statistics, JAMA Oncology
  • 4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
JAMA Oncol. Published online July 23, 2020. doi:10.1001/jamaoncol.2020.1847

Historically, novel postneoadjuvant therapies for patients with early breast cancer have been assessed in multiyear trials. In an effort to address the unmet need of postneoadjuvant therapies in high-risk populations, the US Food and Drug Administration established guidelines for expediting the drug approval process by using pathologic complete response (pCR) as the end point. Previous randomized neoadjuvant trials have suggested that this end point may predict long-term outcome in patients with early-stage breast cancer.1

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Surrogate Endpoints in Cancer Treatment
    Michael McAleer, PhD(Econometrics),Queen's | Asia University, Taiwan
    The important and commendable discussion of using pathologic complete response (pCR)  as the endpoints in scientific oncology clinical trials is analyzed sensitively and clearly in the excellent editorial, with an emphasis on effective treatment of early-stage breast cancer and prostate cancer.

    The difficulty in selecting any surrogate measure lies in assessing its accuracy relative to the effect of treatment on the true endpoint, elimination of symptomatic disease, or reduction in the mortality rate for the individual patient.

    Important issues regarding the sample size, namely the numbers of patients, drugs, events for treatment, appropriate odds ratios, leading to correlations
    (linear or otherwise) of the odds and hazard ratios, need to be tackled rigorously from a scientific perspective, with an emphasis on appropriate quantitative techniques.

    Alternative methods of validation based on altering the surrogate endpoints and the sample sizes are essential to be able to determine the robustness of the clinical trials, especially with regard to reducing false positive diagnoses.

    If the "disease pathways and mechanism of the treatment affect the true clinical outcome and the surrogate end point", assessing the direction of causality would be problematic and misleading.

    This key issue needs to be addressed in determining alternative causal relationships between the surrogate and true endpoints.