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Biomarker studies: a call for a comprehensive biomarker study registry

Nature Reviews Clinical Oncology volume 8, pages 171–176 (2011)Cite this article

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Abstract

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.

Key Points

  • Publication bias and hidden multiple hypotheses testing distort the assessment of the true value of biomarkers

  • Development of a biomarker study registry could decrease publication biases, as shown in the field of therapeutic trials

  • There is a need for a registry that would include all biomarker studies including the negative ones

  • Such a registry could collect key information from each biomarker study, including the main results of the study together with the statistical methods

  • It could be a stepwise project starting with biomarker studies from randomized trials

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Figure 1: Biomarker registry project: initial step and evolution.

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Acknowledgements

The authors thank Mitch Dowsett and J. Milburn Jessup for very helpful discussions.

Author information

Author notes

  1. Centre for Statistics in Medicine, University of Oxford, Wolfson College, Oxford OX2 6UD, UK.

Authors and Affiliations

  1. Department of Medical Oncology and INSERM U981 Institut Gustave Roussy, 39 Rue Camilles Desmoulins, 94805, Villejuif, France

    Fabrice Andre

  2. Biometric Research Branch, DCTD, US National Cancer Institute, Bethesda, 20892, MD, USA

    Lisa M. McShane

  3. Breast Cancer Translational Research Laboratory, Jules Bordet Institute, 121 Boulevard de Waterloo, 1000, Bruxelles, Belgium

    Stefan Michiels

  4. Departments of Medicine and Epidemiology, CB No. 7080, University of North Carolina at Chapel Hill, Chapel Hill, 27599, NC, USA

    David F. Ransohoff

  5. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, SW3 6JB, London, UK

    Douglas G. Altman & Jorge S. Reis-Filho

  6. University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, 48109, MI, USA

    Daniel F. Hayes

  7. Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, PO Box 301439, Houston, 77230–1439, TX, USA

    Lajos Pusztai

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  1. Fabrice Andre
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Contributions

F. Andre, L. M. McShane, S. Michiels, D. F. Ransohoff, D. G. Altman, J. S. Reis-Filho, D. F. Hayes and L. Pusztai all contributed to researching the data for this article, to discussions relating to the article content, writing and reviewing/editing of the manuscript before submission and during the revision process.

Corresponding author

Correspondence to Fabrice Andre.

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Competing interests

D. F. Hayes declares he has personal financial interest (stock ownership, membership on advisory board, on the board of directors and other relationships for Halcyon Diagnostics and Oncimmune LLC. He is also a consultant for Biomarker Strategies, Compendia Bioscience, and Chugai Pharmaceuticals. D. F. Hayes has also received sponsorship or is a principle or co-investigator for trials sponsored by GlaxoSmithKline, Johnson & Johnson, Novartis, and Pfizer. The other authors declare no competing interests.

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Andre, F., McShane, L., Michiels, S. et al. Biomarker studies: a call for a comprehensive biomarker study registry. Nat Rev Clin Oncol 8, 171–176 (2011). https://doi.org/10.1038/nrclinonc.2011.4

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