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Retrospective validation of genomic biomarkers – what are the questions, challenges and strategies for developing useful relationships to clinical outcomes – workshop summary

The Pharmacogenomics Journal volume 6, pages 82–88 (2006)Cite this article

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The material presented in this article is a consensus opinion reached by the authors, which summarizes opinions and views shared during the DIA-FDA-PWG-PhRMA-BIO Pharmacogenomic workshop on ‘Retrospective Validation of Genomic Biomarkers – What are the Questions, Challenges and Strategies for Developing Useful Relationships to Clinical Outcomes’ held in Rockville, Maryland in April 2005. Two sessions were held, each attended by around 200 people from pharmaceutical and diagnostic companies, government agencies, academia and elsewhere, in addition to the seven steering committee members. Participants besides the steering committee members had opportunity to voice their individual opinions. The audience also responded to a series of questions from the steering committee by a show of hands. Qualitative assessment of the results (e.g. consensus/general feeling, most, the majority, 50–50, some, a few and none) was recorded in real time by note takers.

The US Food and Drug Administration, in their recent critical path initiative,1 proposes a number of changes in the process of drug development to increase success in the introduction of new drugs. In this article, we focus on pharmacogenetic approaches that could either enable the approvability or increase the scientific basis for approvability of drug indications. The approach discussed involves the use of clinical data and genetic analyses of DNA samples from previously completed clinical trials to identify a subpopulation within the enrolled trial population that has an improved risk–benefit ratio. The use of samples and data for new analyses not originally declared in a clinical protocol is, on its face, contrary to the standards for drug approval from well-controlled clinical trials. We challenge this assumption using two hypothetical case examples. The case studies raise questions and highlight potential approaches for defining prospective hypotheses and conducting pharmacogenetic analyses that could result in the generation of data that is evaluable in the same way as data generated in a pivotal trial for approval and labeling of drugs.

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Acknowledgements

We thank Dr Jerry Collins of FDA, the Interdisciplinary Pharmacogenomic Review Group of FDA and Dr Richard Simon of NCI for their insightful inputs and constructive comments. The authors also thank Ms Julie Friedman of Bristol-Myers Squibb Co. for taking the notes during discussion.

Author information

Authors and Affiliations

  1. Office of Biostatistics, Office of Pharmacoepidemiology and Statistical Science, Center for Drug Evaluation and Research, US FDA, Silver Spring, MD, USA

    S-J Wang

  2. Johnson and Johnson Pharmaceutical R&D, Raritan, NJ, USA

    N Cohen

  3. Abbott Laboratories, Abbott Park, IL, USA

    D A Katz & B Spear

  4. Genomas Inc., Hartford, CT, USA

    G Ruano

  5. Merck & Corporation, Bluebell, PA, USA

    P M Shaw

Authors
  1. S-J Wang
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  2. N Cohen
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  3. D A Katz
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  4. G Ruano
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  5. P M Shaw
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  6. B Spear
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Corresponding author

Correspondence to S-J Wang.

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Disclaimer

The views presented in this article are those of the individual authors and the opinions are those expressed during the workshop. The views do not necessarily reflect those of the FDA or those of the Genomas Inc., Abbott Labs, Merck & Co., J&J Pharmaceutical R&D.

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Wang, SJ., Cohen, N., Katz, D. et al. Retrospective validation of genomic biomarkers – what are the questions, challenges and strategies for developing useful relationships to clinical outcomes – workshop summary. Pharmacogenomics J 6, 82–88 (2006). https://doi.org/10.1038/sj.tpj.6500363

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