Prospective–Retrospective Biomarker Analysis for Regulatory Consideration: white Paper from the Industry Pharmacogenomics Working Group

Abstract

One approach to delivering cost-effective healthcare requires the identification of patients as individuals or subpopulations that are more likely to respond to an appropriate dose and/or schedule of a therapeutic agent, or as subpopulations that are less likely to develop an adverse event (i.e., personalized or stratified medicine). Biomarkers that identify therapeutically relevant variations in human biology are often only uncovered in the later stage of drug development. In this article, the Industry Pharmacogenomics Working Group provides, for regulatory consideration, its perspective on the rationale for the conduct of what is commonly referred to as the prospective–retrospective analysis (PRA) of biomarkers. Reflecting on published proposals and materials presented by the US FDA, a decision tree for generating robust scientific data from samples collected from an already conducted trial to allow PRA is presented. The primary utility of the PRA is to define a process that provides robust scientific evidence for decision-making in situations where it is not necessary, nor practical or ethical to conduct a new prospective clinical study.

KEYWORDS::

• adequate evidence
• biomarker
• cetuximab
• data analysis
• drug development
• KRAS oncogene
• panitumumab
• prospective analysis
• retrospective analysis

Author disclosure

This article does not necessarily reflect the views of the companies that are members of I-PWG.

Acknowledgements

The authors acknowledge the contribution of Jenny Green for administrative assistance and Charles Lister for legal monitoring (Covington and Burling LLP).

Financial & competing interests disclosure

All authors are employed by pharmaceutical companies that are actively engaged in pharmacogenomic research; collecting, analyzing and storing DNA samples from subjects participating in clinical trials. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

All authors are employed by pharmaceutical companies that are actively engaged in pharmacogenomic research; collecting, analyzing and storing DNA samples from subjects participating in clinical trials. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.