1. 1 FDA Update - CDRH Markham C. Luke, MD PhD Deputy Director for Clinical Office of Device Evaluation, CDRH, FDA May 15, 2012 NORD Corporate Council

2. What is new in CDRH? Guidance on Benefit versus Risk Draft Guidances on IDE Decisions, Early Feasibility, Pivotal Clinical Study Design Pilots for CMS/FDA Parallel Review and Early Feasibility Innovation Pathway 2.0 MDUFA Agreements between FDA and Industry – Commitment Letter

3. Benefit vs. Risk Clarity for FDA reviewers and industry regarding principal factors FDA considers when making benefit vs. risk determinations during premarket review process for certain medical devices (PMA Approvals and De Novo Classifications)

4. Benefit Assessment Type of benefit Magnitude of benefit Probability of a patient experiencing a benefit Duration of effect

5. Risk Assessment Extent of probable risks and harms – Severity, types, number, and rates of harmful events associated with the use of the device Serious and non-serious adverse events Procedure-related complications Probability of a harmful event Duration of harmful events For diagnostics – Risk from false-positive or false-negative results

6. Benefit vs. Risk Certainty of benefits vs. risks – design and conduct of trials, analysis of data, generalizability of the study data to intended treatment and user population Disease characterization –What is the natural history and progression of the disease? –Disease severity and chronicity –Availability of alternative treatment/diagnostic options Patient tolerance for risk and perspective on benefit –“FDA recognizes that patient tolerance for risk and a patient- centric assessment of risk may reveal reasonable patients who are willing to tolerate a very high level of risk to achieve a probable benefit, especially if that benefit results in an improvement in quality of life.” –Sponsors are asked to consider developing such data

7. IDE Draft Guidances

8. Pivotal Clinical Study Draft Guidance Provides information to help guide design of pivotal clinical studies for medical devices.

9. CDRH Pilot Projects FDA/CMS Pilot Review – –Underway –Pilot proposal accepted on first round –Still accepting pilot proposals Early Feasibility IDE Pilot – –Underway –Pilot proposals reviewed and 9 accepted –Closed to further pilot proposals

10. Collaboration PhaseClinical Trials PhaseMarket ApprovalApplication Process FDA Conference Center IT Tools Innovation Pathway 2.0

11. Guiding Principles Create shared understanding of success Use best practices in framing benefit and risk Create solutions that facilitate forward progress Improvise, experiment, prototype, test, and learn Transparency in decision- making Collaboration Phase

12. Map of the envisioned regulatory pathway Identify key decision points that may impact total time Identify scientific and regulatory issues Establish plan for revisiting the roadmap CDRH Network of Experts Vetted network of scientists, clinicians, and engineers Collaboration Phase

13. Clinical Trials Phase Frame benefit and risk Decision support tools –Trade-offs –Makes reasoning explicit and transparent –Incorporate patient perspectives Test decision support tool with first-in- human, then expand

14. Market Approval “ Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications ” Bi-directional feedback to improve regulatory/application performance.

15. Innovation Pathway 2.0 3 Applications Chosen UCSF bioimplantable artificial kidney BPTi Wearable artificial kidney CreatiVasc Hemoaccess Valve System

16. MDUFA III Commitments Commitments made February 17, 2012 on MDUFA Performance Goals and Procedures Includes Language on Patient Safety and Risk Tolerance –Fully implement final guidance benefit-risk determinations in medical device premarket review –Meet with patient groups to better understand and characterize patient perspective on disease severity and unmet medical need. –Increase utilization of Patient Representative Special Government Employee (SGE) consultants –Provide patients’ views early product development process –Ensure those perspectives are considered in regulatory discussions –Screen for conflict of interest –Protect confidentiality of proprietary information

17. Questions Markham.Luke@fda.hhs.gov Michelle.McMurry-Heath@fda.hhs.gov