1. Session II Safe PCI For Women David R Rutledge, Pharm.D., FCCP, FAHA Director, Worldwide Clinical Research Device Industry View

2. Which Ultimately Determines a Medical Device Company’s Success? a)Protocol and ICF Sign-Offs b)SAP and mock table Sign-Offs c)EDC Build with Edit Checks d)Achieving FPI goal e)LPI/LPV goals ahead of timeline f)Database Lock ahead of timeline g)IFU Updates h)Timely, Valid and Positive Data i)NEJM, JAMA, and LANCET Articles j)Final Report k)Large data sets with tens of thousands of patients 2 TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 2013 Abbott Vascular 29JUL13

3. TREAT Experience with a Large Public Databases Tiptoe into a public database –Anonymized patient data back to the patient’s source documents New way of thinking shifting our thinking about a Sponsor’s commitment to “Innovation” –Designing trial then building the database –Accessing the database then designing the trial TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 3 2013 Abbott Vascular 29JUL13

4. Medical Device Companies 4 2013 Abbott Vascular 29JUL13 TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters Issues For Further Discussion Today

5. Tipping Point For Investment Venture Capitalist “You bet on the Jockey not the Horse” Determine the “Tipping Point” between what Device companies can get from a public database and a Sponsor’s willingness to invest TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 5 2013 Abbott Vascular 29JUL13 Overlap Important Ours not Theirs Not Important Theirs not Ours Surveillance 60%??% Label Expansion 30%??% Approval 10%??% What’s our value proposition?

6. 6 Ability to Tweak a Public Database On Demand (Response from Regulator or IRB/EC) –Product specific entry, e.g., expiration date, times –Clarify a safety field –Change in a clinical definition –Concomitant drug therapies Early On During Enrollment –Inclusion/Exclusion criteria –Device line extensions/updates become available –Newer accessories become available –Scientific data become available during the trial, e.g., company or competitor, safety or efficacy TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 2013 Abbott Vascular 29JUL13

7. Initial EDC Build versus Amendment Releases *** Simulation = Set Targets and Negotiate *** 7 Activity Fully Executed (10 wks.) Amendments Executed (3 wks.) Requirements = Determine the requirements from the protocols $ 5,000$2,000 Specifications = Data Management (translate from protocol to eCRF spec) $ 50,000 $ 30,000 EDC Programming (Implementation of change into database) $ 50,000 $ 20,000 Validation (Outsourced ) $ 50,000 $ 30,000 UAT (User Acceptance Testing) $ 15,000$ 5,000 Integration Programming * Safety Database (EDC-Commercial) * IVRS * Inventory * Payments $ 50,000 $ 15,000 Release $ 15,000$ 5,000 TOTAL $230,000$107,000 TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 2013 Abbott Vascular 29JUL13

8. Is There an Appetite to Waive Portions of GCP ICH-E6 5.5.3a-g? 5.5.3 When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should: (a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation). (b) Maintains SOPs for using these systems. (c) Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data (i.e. maintain an audit trail, data trail, edit trail). (d) Maintain a security system that prevents unauthorized access. (e) Maintain a list of the individuals who are authorized to make data changes (see 4.1.5 and 4.9.3). (f) Maintain adequate backup of the data. (g) Safeguard the blinding, if any (e.g. maintain the blinding during data entry and processing). 8 2013 Abbott Vascular 29JUL13 TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters   

9. Medical Device Approval Trials Medical Device companies prefer to focus on “Out of Control Group” TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 9 2013 Abbott Vascular 29JUL13 Value of Large Public Databases Construct Performance Goals or Objective Performance Criteria for smaller, single-arm studies

10. Issues For Further Discussion Standard Definitions Once you go beyond one database, there are no standard definitions for data elements, e.g., sex/gender/gender at birth, MI, Race/Cultural Origin, Renal Failure/SrCr, Date of Birth/Day of Birth Research Community By the time the DB gets large and robust, the research community has gone forward, e.g., “Practice lags behind research.” PARTNERSHIP What does “partnership” mean? Strategic Partnerships? What is the legal framework? TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 10 2013 Abbott Vascular 29JUL13

11. Audit Readiness? TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 11 2013 Abbott Vascular 29JUL13 No clear ownership and accountability of database

12. Issues For Further Discussion (cont.) How do we improve site relationships/management? –Sites get upset too –They are busy Are screening failures more easily accessible? Is this a real aid to site selection? –Experience and expertise of the interventionalist –PI resources to conduct study –Cross discipline expertise for the interventionalist Is this a real aid to patient selection? 12 2013 Abbott Vascular 29JUL13 TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters

13. 13 Benefits vs. Risks: Public Database Risks to Medical Device Companies Benefits to Companies High Moderate Low High Moderate +++ ++++ +++ ---- --- ++/-- ++/- +/-- Can FDA, public databases, and medical device companies mitigate factors for cost-effective IDE approvals? TREAT IV Transradial Workshop Fourth Thinktank at FDA Headquarters 2013 Abbott Vascular 29JUL13