Ethical issues with the regulatory use of gene expression data

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
Clinical applications
Pharmacogenomic research

• 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
Confidentiality Independence Authority
IRB Public Internal Determinative
DMC Private External Determinative
FDA Advisory Committee Public External Advisory
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