1. Ethical issues with the regulatory use of gene expression data Benjamin S Wilfond MD Medical Genetics Branch National Human Genome Research Institute Department of Clinical Bioethics Warren G Magnuson Clinical Center

2. The Regulatory Challenge Pharmacogenomic research Clinical applications  When is it appropriate to use this data for  Drug approval process  Clinical decision making

3. FDA proposal  Regulatory Use  When sponsor intends to use the data to  Demonstrate safety or efficacy (clinical trials)  Recommend clinical applications (clinical testing)  “Research Use”  Unique genes  Gene expression profiles

4. “Develop thresholds and policies using public and transparent process with advisory committee oversight”  Thresholds for biological validity and clinical relevance  But what process will be used to determine if the threshold is reached in a particular case?

5. Decision categories  Policy Decisions  Categories of studies (ie types of data)  Thresholds for inclusion of data  Application Specific Decisions  Data requests  Data evaluations  Both decision categories would benefit from review of research data

6. Interdisciplinary Pharmacogenomic Review Group (IPGRG)  Primarily focused on policy  Could also consider specific drug application decisions  Could refer specific drug application decisions to another group

7. Procedural Options  Confidentiality: Public vs private  Independence: Internal vs external  Authority: Advisory vs determinative

8. Examples ConfidentialityIndependenceAuthority IRBPublicInternalDeterminative DMCPrivateExternalDeterminative FDA Advisory Committee PublicExternalAdvisory

9. Procedural choices depend on underlying objectives  Confidentiality  Public - greater accountability and transparency  Private- greater willingness to share data  Independence  Internal - greater familiarity  External - greater objectivity  Authority  Recommendation - greater acceptability to skeptics ( still requires determination of decisional authority)  Determinative - greater enthusiasm for participation

10. Next steps  The choice between procedural options includes ethical consideration of the tradeoffs between different options  Decide if IPGRG would decide about specific applications or refer to second group  Decide about confidentiality, independence, and authority of either or both groups