What Does Personalized Medicine Mean for Developing, Commercializing, and Regulating Medical Technology?

1. What Does Personalized Medicine Mean for Developing, Commercializing, and Regulating Medical Technology? Richard Naples March 28, 2008

2. Personalized Medicine Topics • Challenges Confronting Personalized Medicine (PGX) • Regulatory and Reimbursement Issues • Help is on the Way • AdvaMed Proposal for Least Burdensome • Conclusions

3. Challenges Confronting PGX • Recent JAMA Commentary: • Lack of information on prevalence and risk conferred by genetic markers across population groups • Limited data on inheritance of multiple markers and effects on risk of disease • Incomplete picture of how genetic risk factors interact with environmental factors Source: JAMA, 3/19/08, Drs. Feero, Guttmacher, and Collins

4. Challenges Confronting PGX • Recent JAMA Commentary, cont. • Not enough studies on common diseases and effect of interventions based on genetic risk factors • Limited evidence of benefit of personalized medicine, especially since there are no clinical studies • Fear of genetic discrimination Source: JAMA, 3/19/08: Drs. Feero, Guttmacher, and Collins

5. Challenges Confronting PGX • Additional Challenges • Regulatory Pathways - Two routes to market that are not created equal • FDA-regulated IVD kits • CLIA ’88 Lab Service • Reimbursement – local and national coverage decisions

6. Regulatory Challenges • Over the past 30 years most new diagnostics have come to market as kits through FDA • Recently over 1000 new genetic tests marketed as laboratory developed tests (LDTs) under CLIA ’88 • Timely patient access, but…. • No independent premarket review* • Little public data on safety and effectiveness • No postmarket studies to demonstrate value • Direct to Consumer testing (exempt from CLIA ’88 authorities?) – buyer beware! * Except NYSDOH review for tests offered to NY residents

7. Regulatory Challenges • FDA clearances/approvals • 58 genetic tests • 82 newborn screening tests • Several dozen infectious diseases • Personalized Medicine • Herceptin (Her2/Neu) • Anti-depressants/anti-psychotics (cyp450) • Camptosar (UGT1A1)

8. Reimbursement Challenges • Aetna Clinical Policy Bulletin Pharmacogenetic Testing Coverage Number #0715 • Genotyping for P450 polymorphisms is experimental and investigational • Invader UGT1A1 molecular assay is experimental and investigational • Genotyping for VKORC1 polymorphism is experimental and investigational • Genotyping for HLA-B 1502 medically necessary Source: Aetna Clinical Policy Bulletin Pharmacogenetic Testing Coverage Policy #0715; Policy History/Updated 03/07/2008

9. Help is on the Way • FDA Guidance for Industry • Pharmacogenomic Data Submissions • In Vitro Diagnostic Multivariate Index Assays (IVDMIAs) • Analyte Specific Reagents (ASRs) • HHS Personalized Health Care Initiative • Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS) • Alternative Industry Proposals • 21st Century Coalition • American Clinical Laboratory Association (ACLA) • AdvaMed Least Burdensome Approach

10. Common Themes • Gaps in federal oversight • Clinical validity • Clinical utility • Cost issues – cost effectiveness, comparative effectiveness, etc.

11. Different Solutions • FDA oversight limited to high risk tests and companion diagnostics • Enhanced CMS CLIA ’88 oversight with consultation by FDA • Voluntary or Mandatory Genetic test registries • Public/Private partnerships to review clinical utility

12. AdvaMed’s Least Burdensome Approach • AdvaMed’s Seven Principles For Timely Access to Safe and Effective Diagnostics • Principle #1 – All clinical labs should be subject to CLIA requirements and quality standards • Principle #2 – FDA should oversee safety and effectiveness of all diagnostic tests no matter where they are made, because they have the same/risk benefit profile for patients

13. AdvaMed’s Seven Principles • Principle #3 – Least Burdensome ApproachFDA oversight should focus primarily on the potential risk of harm associated with how the test result is used to treat patients, not the technology of the method

14. AdvaMed’s Seven Principles • Principle #3 Continued • Low risk tests and moderate risk well- standardized tests should be exempt from FDA premarket review • High risk tests should be subject to a risk-based review that aligns review intensity/data requirements with potential risk of harm to patient

15. AdvaMed’s Seven Principles • Principle #4 – Patient access to specialized test categories, i.e., rare diseases and rarely used tests should also be exempt • Principle #5 – FDA and CMS should harmonize regulatory requirements and leverage each other’s standards and resources for regulatory oversight of lab developed tests

16. AdvaMed’s Seven Principles • Principle #6 • The new regulatory oversight system should be implemented through notice and comment rulemaking and guidance as appropriate • Device classification exemption panels • Least burdensome reviewer guidance

17. AdvaMed’s Seven Principles • Principle #7 • CMS and private payors must implement a new payment paradigm for emerging diagnostics

18. Conclusions • New Regulatory and Reimbursement Paradigms Needed for Emerging Diagnostics • Timely Patient Access to safe and effective diagnostics • Public information on the analytical validity, clinical validity, and clinical utility for all diagnostic tests • Value-based payment policies that support innovation