1. Ralph F. Hall October 14, 2014

2. Background and Disclosures Develop policy solutions Coalition management Consulting services Partner – Leavitt Partners Advise clients on FDA regulatory matters, compliance issues and regulatory policy issues Counsel – Faegre Baker Daniels Professor of Practice Supported in part by NSF and NIH Grants University of Minnesota Law School Start up medical device company Probably PMA pathway if product successful CEO – MR3 Medical LLC 2

3. Overview Medical/scientific/clinical questions elicit the greatest attention Legal structures needed to allow entity to succeed As role of MDEpiNet changes, legal requirements change ─ Moving from an academic project changes requirements ─ External funding creates new challenges Failure to address legal requirements threatens success 3

4. Overview Objective is to identify, not resolve questions ─ Stakeholder concurrence vital Requirements fall into four categories 1.Governance issues 2.Patient centric challenges 3.Regulatory matters 4.Other legal questions 4

5. Governance Questions Who decides who manages the enterprise? ─ CEO and senior management  Succession ─ Board of Directors (or equivalent) ─ Can standard academic appointment processes meet the needs of a multi-stakeholder enterprise? ─ Accountability Conflict of interest and role issues ─ Board and senior management ─ Funding sources ─ Agency involvement Transparency 5

6. Patient Centric Questions Informed consent ─ State law controls many informed consent requirements ─ Role of consent; when is it needed ─ Historically cannot consent to future or undisclosed research ─ “De-identification” may not solve consent requirements ─ Withdrawal of consent/opt out of research ─ Role of patient autonomy and patient centric medicine ─ Value proposition for patient ─ Children and geriatric patients Family and cross-generational issues Transparency and access to data 6

7. Patient Centric Questions Return of research results ─ Should registry return research results to patient (or patient health care professional)? ─ Patient and system expectations ─ Is there any rational for not returning research results Return of incidental findings ─ Patient and system expectation Ability to unblind Liability for failure to inform 7

8. Regulatory Issues Use of registry data in pre-market context ─ Support for submissions ─ Role of controls, blinding, etc. ─ Consent requirements ─ Agency review (“bimo” inspections) Use of registry data in post-market context ─ Formal post-market uses  522 orders  Conditions of approval ─ General obligations  Adverse event reporting  CAPA systems 8

9. Regulatory Issues Recalls and safety issues Identification of issues ─ Obligation to assess data  May increase with roles in 522 and similar schema ─ Reporting to company ─ Reporting to agency ─ International obligations Participating in recalls ─ Patient or HCP notification Role in physician and hospital performance assessments Role in payment and cost effectiveness decisions 9

10. Legal Issues Fraud and abuse/antikickback issues ─ Attention from OIG Sunshine Act reporting Privacy issues ─ International differences Role of registries in litigation ─ Discovery requests “Pay to play” and FACA issues IP rights International use and issues Transparency requirements Interactions between registries 10

11. Conclusion and Questions Issue Identification Stakeholder Involvement Issue Resolution 11