Building and Maintaining a Sound Clinical Research Program

Building and Maintaining a Sound Clinical Research Program Louis A. Cannon, MD, FCCP, FSCAI, FACC, FACP Sr Program Dir, Heart & Vascular Institute of Mc. Laren Northern Michigan President, Cardiac & Vascular Research Center of Northern Michigan

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. • Consulting Fees/Honoraria • Major Stock Shareholder/Equity • • • Company Boston Scientific Abbott Medtronic Covidien Founder and President, CVRCNM Bio. Star Ventures BOD of KONA BOD of Auto. Nomix BOD CVI acquired by Covidien / MDT Equity ASI I am expressing my opinions not necessarily facts and the opinions are not necessarily those of my medical centers or businesses

CVRCNM Mission Statement • • Make a difference in pt’s healthcare and longevity, while improving the safety and efficacy of medical devices and Trx Ensure that Access to Cutting Edge Care in our Community was equal to some of the best Research Centers in the world To not impose an economic burden on our hospital or system Consistently be in the top ten enrollers in all major studies • • • No Fellows 200 Beds Swell in the summers Freeze in the winters Top Tier Cardiologists -- Beauty, Huge Referal Base, and the quality of practice Protocol Assessment – Is it a Match for your research Center

Protocol Selection • Key to: – Competing Studies – Don’t waste everyones time – Protocol Assessment – Financial Viability and Enrollment Probability – Investigator Interest • Score Card for evaluation

Protocol Phase of Study Phase III Phase IV Post Market Study Application IDE IND Standard of care Scientific Strength Novel (no FDA comparator) 2 nd Generation similar to FDA product Broaden FDA Label use Field of Practice Primary Field of Practice Secondary Field of Practice 10 10 3 10 10 7 7 3 4 Field of Practice Enrollment 2 -10 Phase of Study 12 Study Application 10 8 6 4 Scientific Strength 2 0 Follow-up 4 Patient Safety/Risk Screening Pattern 5 10 10 Medically indicated w/o options Significant risk 8 Medically indicated w/o options High risk 6 Within established screening pattern Modified Screening pattern New Screening pattern Enrollment Ability to enroll 4 -8 month Ability to enroll 2 -4 month Ability to enroll 1 month Follow-up In patient + Out patient Follow Complexity Office visit w/o phy Offfice visit /w phy office visit /w Labs Office visit /w diagnostic office visit /w infusion Complex Diagnostic Follow-up Commitment ≤ 90 days ≤ 180 days ≤ 1 year ≤ 2 years > 2 years Follow-up Commitment Follow Complexity 10 8 Healthy Volunteer with nominal risk Medically indicated with High Risk Medically indicated Screening Pattern Protocol 10 7 3 1 Outside of practice, /w 1 st Field req't Outside of Practice, /w 2 nd Field req't Outside of Practice Patient Safety/Risk Medically indicated nominal risk Score Protocol 5 10 10 8 -10 10 10 5 -10 Follow-up Commitment Follow Complexity 5 5 10 2 10 8 7 5 4 2 Follow-up Field of Practice Enrollment Patient Safety/Risk Screening Pattern 10 10 9 7 5 2 Phase of Study 0 Study Application 2 4 6 8 Scientific Strength 10 12

Financial Burden Sponsor Established, publicly traded LLC Start Company Study Model Blinded by sponsor Blinded by Site Registry Investigational Product Provided Not Provided - discount Not provided - full cost 10 5 2 10 3 0 Lenth of Stay Within the Standard of Care Outside the Standard of Care Inventory Shelf Life >180 days 90 -179 days 45 -89 days <44 days Patient Billing non blinded billing Blinded Billing Investigation Product Oral Infusions Injections Permanent Implant End of life Device Follow-up Local Labs Core Labs Local Diagnostic Complex Diagnostic Coordinator Time Commitment Consent Ratio > 5: 1 Consent Ration 1: 1 Reimbursement None Break Even Yield <10% Yield >10% 10 3 10 8 2 -10 10 3 10 8 8 8 2 10 2 10 10 -50 0 5 10 5 3 10 10 10 Financial Burden Sponsor 12 10 8 6 4 2 0 Reimbursement Coordinator Time Commitment Study Model Investigational Product Series 1 Follow-up Lenth of Stay Investigation Product Inventory Shelf Life Patient Billing 10 Financial Burden 8 Reimbursement 10 Coordinator Time Commitment 10 5 Sponsor 0 2 4 6 8 10 12 Follow-up Study Model Investigational Product Lenth of Stay Investigation Product Inventory Shelf Life Patient Billing

Score Card (Protocol + Financial Burden + Desire) 0 Financial Burden 2 Protocol + 4 Sponsor Reimbursement 6 Principal Investigator Desire Study Model 8 Coordinator Time Commitment 10 Investigational Product 12 Follow-up Commitment Follow Complexity Phase of Study 0 2 4 6 8 10 12 Follow-up Study Application Lenth of Stay Investigation Product Patient Billing Scientific Strength Field of Practice Patient Safety/Risk Enrollment Screening Pattern Inventory Shelf Life + = !00%

Protocol is a go : Script It ! • Start to finish: • Screening/Consenting/Enrollment/Randomization • Procedure Requirements / Data Collection • Detailed Orders for the protocol thru Patient D/C • Letter to Referring Physician with any cautions • Notify Hospital Accounting & Practice of enrollment – Ensure the IDE#/IND# is added to patient billing – CMS (part A & B) and FDA strong Relationship » Success with expediting the process » Expediting Resolution between CMS/FDA/Sponsor

Working Smarter • • Doing “more” with “less” Organization Communication About “Leaving a Trail” – Documentation for • Documentation for Everyone: Hospital, Billing, JCHA, FDA • Screening Consenting Enrollment 20 -10 -1 Rule

Cath Lab 3 Board Keeping the Cath Lab & Doctors informed: Add Ons don’t get “added on” until research clears them 7: 30 Smith, John Cath/poss LAC 7: 30 Doe, John Cath/poss LAC 8: 00 Jones, Mary Cath/poss LAC 8: 00 Miller, John Cath/poss LAC 8: 30 Jackson, Mary Cath/poss LAC 8: 30 Johnson, John Cath/poss LAC 9: 00 Hall, Robert Cath/poss LAC = Screen Failure – Not Consented Patient = Consented Research Patient

Administrators: Research Awesome but show Me Da $$$$ • Hospital Administration • Consider “cost” of research » » » Risk and Benefits to the institution Consider Patient Population Solely Research related Procedures Incentivize, Incentivize for the right things Research is not 8 AM – 5 PM CVRCNM is FOR PROFIT –we are what we are • Research can be Black rather then RED • • Cover solely research related costs Provide reimbursement at FMV Work with companies to assist in costs Never compromise your name or ethics

Separate Research Fact from Research Fantasy

Summary of CV Research Benefits Physicians Hospital • Strategic connections • Research Expertise • Site Management Sponsor • Increased National Recognition • Keep Physicians Engaged • Community Awareness • Decreased Device Costs • Increased Research Fees • Procedure Volume & f/up • Legal Risk with Central IRB • Operationalize and IRB vs MRC • Media and Market • Nationalize Reputation • Academic Strength • Research Drag Along • Integrate System collaboration • Recruit and Retain Quality • Alternate revenue Sources Contract Negotiations Regulatory Compliance Trial Management Recruitment Plan • Co-Manage the Business • Stay up to date • Collaborate • Time Away from Family • Time Away from Practice • Mtg attendance • Networking • Publish • Editorial Boards • Partnership of Expertise • Simplified Regulatory with Central IRB, ↓ Risk • Quick Start-Up • Institutional Commitment • 30 Days (CDA to 1 st Enroll) • Compliance • Organization • ↓Monitoring Time • ↓Protocol Deviations • Audit Ready • ↓ Sponsor “out-of-pocket” cost • “Strategic Vendor Relationship”

Monitoring • Query resolutions is the best “Barometer” for determining if your site is on track • Post Monitoring Visit – I always re-group with the staff » What we need to adjust in the enrollment plan: over screening, under-screening, consent “mantra” revision » What we are doing right » Where are we exposed » What we can we do better

It is Going to Take Lots of Work and Partnerships Important Hospital Admin Mtgs

Thank You Thank you

Research is a Team Effort: Lay down a strong foundation and give your sites “longevity” Thank you

People / Team Drives Research High Quality, Board Certified, Multi-disciplinary Relationships : ACRP, NIH, Haz. Mat, CCRI, DCRI, HCRI Commitment & Longevity & Passion Physicians that will Disrupted Silos for Research Physician Dedication to off hours (No Fellows) Staff Dedication (PK Studies) Flexible Hotels, travel, blood draws etc…

Research Driven By Quality • Internationally Acclaimed Cardio. Vascular • Providing Cutting-Edge Therapy • No Fellows Advancing Medicine with Science • FDA confirmation of Quality : 7 Audits • Widespread commitment to research • Lectured WORLD Wide even CRT • $ Millions in Profit for our System • Hundreds and Hundreds of Publications Hospital is <200 Beds