Translational Research : University of Iowa July 22, 2013

1. Translational Research:University of IowaJuly 22, 2013 Bruce Gingles Vice-President Cook Medical, Inc bruce.gingles@cookmedical.com

2. Translational Research “Research that benefits at least one person outside the researcher’s laboratory, and preferably a patient” “Research is scientific, translational research is economic” R01→ROI

3. Succeeding at researchFailing at translation Four phases of translational research*: • T1: Phase I and II clinical trials and observational studies • T2: Phase III clinical trials and observational studies; evidence synthesis and guidelines development • T3: Dissemination research; implementation research; diffusion research; Phase IV trials • T4 Outcomes research * Khoury et al. Genet Med 2007; 9(10): 665-674

4. yh

5. Moore’s law and technologic innovation

6. Moore’s Law and FDA • January-July 1999: 17 PMAs and supplements approved • January-July 2009: 12 approvals, -29% • 1998 full year: 42 approvals • 2008 full year: 24 approvals, -43%

7. Impact on Cook • Innovators have increasingly shifted from being independent to indentured inventors within a changing legal architecture. Manufacturers now frequently negotiate with third parties for property rights. • Dedicated federal, state and institutional funding intended to result in a larger pool of discoveries and disclosures, to which Cook seeks access. • Technologies licensed from AMCs have halo effect.

8. The model for basic research is funded grants, published research, career advancement and properly staffed medical schools competent to perpetuate federal funding, train students and deliver patient care. The benefit to society is a stable academic health system.

9. The model for translational research is invention, patent(s), licensing/royalties (or start-ups), with revenue reinvested in the university. The benefit to society is new cures and advanced medical care. Discoveries must be unitized, monetized, taxed and exported to achieve optimal economic utility and public benefit.

10. Why invent? • Better patient outcomes and improved public health • Extends medical impact on patients globally • Intellectually stimulating • Remunerative • Academic promotion/Institutional benefit through technology transfer process • Legacy

11. Why not invent? • Fear of being fleeced, ignored or corrupted • Loss of academic or professional reputation • Poor understanding of the process

12. Common Expectations of Inventors by Industry • Product design input • Assistance with regulatory applications • Perform/advise clinical evaluation • Publication/presentation in peer-review • Patents/licensing • Patronage

13. Common Expectations of Industry by Inventors • Timely product development cycle • Prompt and honest communication • Financial support of development, research and presentation costs • Strong marketing effort • Upgrade/modify product as needed • Compensation

14. Royalties • Paid for the life of licensed patents, 20 years • May be paid in the absence of patents, for defined periods of time, typically 6-10 year intervals • Customary rates range from 1½-8% of net sales, with an average of 3%. May be paid quarterly or annually

15. Conflicts of Interest • Simply, if you receive royalties, research grants, salary or professional fees (FFS), $COI exists • Misconduct is more important than COI. Presumption of innocence? (PPSA) • Perception is a fallible standard • Royalties not paid on sales to inventor’s hospital • Type I and Type II risk and error

16. Relationships with Industry • Industry possesses resources and expertise indispensible to the development and commercialization of technologic innovation • Technologic innovation depends on close working relationships between inventors and manufacturers • These relationships are ethical, professional and as altruistic as FFS

17. Typical Development Cycle • Idea submitted under non-disclosure • Reviewed for acceptance based on benefit to patients, total economic value, ROI • Coding and reimbursement are issues today • FDA filing fees: 510(k) $4,158 /PMA $281, 600 MDUFMA, 2002. CE mark • IRB→Prototype evaluation • Quality system design review→production • Market release (average 510(k) cycle time: 35m, PMA: 70m)

18. How to Begin • Identify corporate partner: web pages, medical symposia exhibitions, sales representatives, phone corporate product development, referral from colleagues, http://i2iconnect.org. • Resources vs. bureaucracy • Agree on expectations up front

19. Common Expectations by Universities • Technology Transfer*: Royalties typically divided 35% to PI, 15% to PI’s lab, 15% to the department, 30% to the school and 5% to the university. • MIT faculty and alumni alone have founded more than 4,000 companies and these generate more than $230 billion in annual sales, ranking as the 23rd largest economy in the world.ª • * Read, The Research Brass Ring, Patrick A. Gilbert, Hopkins Health, Fall, 2004 • ª Read, As the Future catches You, Juan Enriquez

20. Patents granted by USPTO in 1985 • Argentina 12 • Venezuela 15 • Brazil 30 • Mexico 35 • South Korea 50

21. Patents granted by USPTO in 2003 • Venezuela 20 • Argentina 70 • Mexico 92 • Brazil 180 • South Korea 4,132

22. Real wages in South Korea multiplied ninefold between 1960 and 1990 Real minimum wage in Mexico was unchanged between 1960 and 2000 South Korea’s real economic growth was eight times larger than Mexico’s between 1990 and 1998

23. 2003 • 17 countries generated 95% of all US patents • 188 other countries generated the other 5%

24. The University of California alone spends 21 percent more on R&D than the entire country of Mexico…… • ……and generates six times as many US patents • In 2004, Pfizer spent over $7.4B on R&D

25. Three essential elements of innovation: • Invention: Concept, prototype, validation (including research), regulation, production • Education: Understand indications, contraindications, potential complications, patient selection, interactions, timing, technique, references, etc. CME • Commercialization: Innovation must be accessible to be useful. Adoption

26. “Invention-driven research is vastly superior to research-driven invention”

27. Why medical devices? • Shorter time to market than drugs • Longer patent life and royalties than drugs • Requires fewer capital resources than drugs • High direct involvement by the inventor, throughout the product lifecycle • Rich EBM, CER and research opportunities* * RO Darouiche et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999;340:1-8

28. Industry-sponsored research funding • Early-stage product R&D • Clinical research funding • Physician training and education • HTA, CER and economic research- priority • Intake forms and compliance •  Inter-organizational familiarity→  projects

29. Two whopping barriers to device innovation • (FDA-cleared/approved) clinical prototype evaluation, performed by the inventor • Commercial adoption at the inventor’s hospital

30. “The best way to predict the future is to invent it” -Alan Kay, 1971