Alyson Haslam1, Spencer P Hey2, Jennifer Gill3, Vinay Prasad4. 1. Knight Cancer Institute, Oregon Health & Science University, USA. Electronic address: haslama@ohsu.edu. 2. Program on Regulation, Therapeutics, and Law (PORTAL), Brigham and Women's Hospital, Center for Bioethics, Harvard Medical School, USA. 3. Knight Cancer Institute, Oregon Health & Science University, USA. 4. Division of Hematology Oncology, Knight Cancer Institute, Oregon Health & Science University, USA; Department of Public Health and Preventive Medicine, Oregon Health & Science University, USA; Senior Scholar in the Center for Health Care Ethics, Oregon Health & Science University, USA; Division of General Medicine, Department of Medicine, Oregon Health & Science University, USA.
Abstract
BACKGROUND: Surrogates are frequently used in cancer medicine as the end-point of clinical trials and as the basis of United States Food and Drug Administration approvals, but they do not always represent outcomes that are important for patients. We aim to build upon previous umbrella reviews of surrogate validation studies by identifying and examining all meta-analyses of randomised controlled trials that evaluate the strength of correlation between overall survival (OS) and surrogate markers. METHODS: Google Scholar and PubMed were searched by two independent reviewers for all eligible meta-analyses of randomised controlled trials examining the correlation between a surrogate end-point and OS in medical oncology. Included studies were trial-level (level-1) meta-analyses of randomised controlled trials in cancer. Data abstracted include date of publication, tumour type, setting, trial set, number of studies included in the analysis, dates of included publications, correlation coefficients and method to determine the correlation coefficient. RESULTS: Seventy-eight articles met the inclusion criteria and reported correlations in 89 settings. Eleven (12%) of these validation studies found only high correlation(s), while nine (10%) settings showed a moderate-only correlation. Thirty-four (38%) reported only low correlation(s). Thirty-five (39%) reported correlations of different strengths, depending on surrogate marker used and test of correlation. CONCLUSIONS: In this large, umbrella analysis of surrogate validation studies, we found most surrogates in oncology had low or modest correlation with OS, which suggests that caution should be used when making conclusions based on surrogate markers.
BACKGROUND: Surrogates are frequently used in cancer medicine as the end-point of clinical trials and as the basis of United States Food and Drug Administration approvals, but they do not always represent outcomes that are important for patients. We aim to build upon previous umbrella reviews of surrogate validation studies by identifying and examining all meta-analyses of randomised controlled trials that evaluate the strength of correlation between overall survival (OS) and surrogate markers. METHODS: Google Scholar and PubMed were searched by two independent reviewers for all eligible meta-analyses of randomised controlled trials examining the correlation between a surrogate end-point and OS in medical oncology. Included studies were trial-level (level-1) meta-analyses of randomised controlled trials in cancer. Data abstracted include date of publication, tumour type, setting, trial set, number of studies included in the analysis, dates of included publications, correlation coefficients and method to determine the correlation coefficient. RESULTS: Seventy-eight articles met the inclusion criteria and reported correlations in 89 settings. Eleven (12%) of these validation studies found only high correlation(s), while nine (10%) settings showed a moderate-only correlation. Thirty-four (38%) reported only low correlation(s). Thirty-five (39%) reported correlations of different strengths, depending on surrogate marker used and test of correlation. CONCLUSIONS: In this large, umbrella analysis of surrogate validation studies, we found most surrogates in oncology had low or modest correlation with OS, which suggests that caution should be used when making conclusions based on surrogate markers.
Authors: Richard M Goldberg; Richard Adams; Marc Buyse; Cathy Eng; Axel Grothey; Thierry André; Alberto F Sobrero; Stuart M Lichtman; Al B Benson; Cornelis J A Punt; Tim Maughan; Tomasz Burzykowski; Dirkje Sommeijer; Everardo D Saad; Qian Shi; Elisabeth Coart; Benoist Chibaudel; Miriam Koopman; Hans-Joachim Schmoll; Takayuki Yoshino; Julien Taieb; Niall C Tebbutt; John Zalcberg; Josep Tabernero; Eric Van Cutsem; Alastair Matheson; Aimery de Gramont Journal: J Natl Cancer Inst Date: 2022-06-13 Impact factor: 11.816
Authors: Joseph Abi Jaoude; Ramez Kouzy; Ethan B Ludmir; Cullen M Taniguchi; Marc Ghabach; Roshal Patel; Dario Pasalic; Elie Ghossain; Austin B Miller; Timothy A Lin; Vivek Verma; C David Fuller; Vivek Subbiah; Bruce D Minsky Journal: BMC Cancer Date: 2021-06-12 Impact factor: 4.430