Nature Reviews Clinical Oncology 8, 171-176 (March 2011) | doi:10.1038/nrclinonc.2011.4

Subject Categories: Targeted therapies | Medical Oncology

Focus on: personalized medicine

Biomarker studies: a call for a comprehensive biomarker study registry

Fabrice Andre, Lisa M. McShane, Stefan Michiels, David F. Ransohoff, Douglas G. Altman, Jorge S. Reis-Filho, Daniel F. Hayes & Lajos Pusztai  About the authors


Tumor biomarker studies may generate insights into the biological characteristics that drive the clinical behavior of a cancer. Publication bias and hidden multiple hypotheses testing distort the assessment of the true value of biomarkers. Publication bias from preferential reporting of 'positive' findings is well recognized. Hidden multihypothesis testing arises from several biomarkers being tested by different teams using the same samples. The more hypotheses (that is, biomarker association with outcome) tested, the greater the risk of false-positive findings. These biases inflate the potential clinical validity and utility of published biomarkers while negative results often remain hidden. Trial registries have been developed where all phase II and phase III trials should be listed regardless of study outcome. However, such steps have not been taken to reduce such bias in tumor biomarker research. We propose that a registry should be created for biomarker studies initially focused on studies that use specimens from randomized trials. Further development could include nonrandomized studies and deposition of raw data similar to existing genomic data repositories. The benefits of a comprehensive biomarker study registry include more balanced evaluation of proposed markers, fewer false positive leads in research, and hopefully more rapid identification of promising candidate biomarkers.

Author affiliations

F. Andre, L. M. McShane, S. Michiels, D. F. Ransohoff, D. G. Altman, J. S. Reis-Filho, D. F. Hayes & L. Pusztai
Department of Medical Oncology and INSERM U981 Institut Gustave Roussy, 39 Rue Camilles Desmoulins, Villejuif 94805, France (F. Andre).  Biometric Research Branch, DCTD, US National Cancer Institute, Bethesda, MD 20892, USA. (L. M. McShane).  Breast Cancer Translational Research Laboratory, Jules Bordet Institute, 121 Boulevard de Waterloo, 1000 Bruxelles, Belgium (S. Michiels).  Departments of Medicine and Epidemiology, CB No. 7080, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA (D. F. Ransohoff).  Centre for Statistics in Medicine, University of Oxford, Wolfson College, Oxford OX2 6UD, UK.  The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, SW3 6JB, London UK (D. G. Altman). (J. S. Reis-Filho).  University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA (D. F. Hayes).  University of Texas, MD Anderson Cancer Center, Department of Breast Medical Oncology, PO Box 301439, Houston, TX 77230–1439, USA (L. Pusztai).

Correspondence to: F. Andre

Published online 2 March 2011