1. "What You Need to Know Before Beginning Your Clinical Trial" FDA Breakfast Briefing October 23, 2002 FDA Counsel.com

2. Financial Disclosure – Duties and Strategies for Clinical Studies Michael A. Swit, Esq. Law Offices of Michael A. Swit 539 Samuel Ct. Encinitas, CA 92024 760-815-4762; fax: 760-454-2979 mswit@fdacounsel.com FDA Counsel.com

3. Financial Disclosure – the Basics Goal -- Reduce potential for bias in clinical studies and enhance human subject protection How implemented FDA Rules @ 21 CFR Part 54; Feb. 2, 1998 – published in F.R.; effective 1 year later FDA Guidance: “Financial Disclosure by Clinical Investigators” – March 20, 2001 FDA Counsel.com

4. Basics… Requirements – for any application (NDA, PMA, BLA, etc.) submitted after effective date, applicant must: disclose data on the “financial interest” of “clinical investigators” of “covered clinicals studies; or certify there are NO disclosable interests FDA Counsel.com

5. Basics… “Clinical investigators” – covers: Principal investigators Sub-investigators named in 1572 spouses and dependent children exempted: per March 2001 Guidance -- “nurses, residents, or fellows and office staff who provide ancillary or intermittent care but who do not make direct and significant contribution to the data” FDA Counsel.com

6. Basics… The Five Basic “Financial Interests” subject to disclosure -- Direct payments > $25,000 -- aka “Significant Payments of Other Sorts” or SPOOS excludes costs to conduct the clinical studies includes honoraria, grants to fund ongoing research, compensation for or in the form of equipment or services, or retainers for ongoing consultation disclosure (for all interests) must be made during the “covered” clinical trial and for one year following completion of the trial FDA Counsel.com

7. Basics … The Five “Financial Interests” … Equity interest of more than $50,000 in a publicly traded company Ownership interest, stock, stock option or other financial interest, no matter how small, the value of which cannot be readily determined through reference to public prices (e.g., any privately held company or unlisted equity interests) FDA Counsel.com

8. Basics … The Five “Financial Interests” … Proprietary interest in the investigational product including, but not limited to, patents, copyrights, trade secrets, and licenses Financial arrangements under which the compensation (e.g., money, equity interest, royalty interest) could be higher for a favorable trial outcome than for an unfavorable trial outcome FDA Counsel.com

9. Basics … “Covered Studies” – trials FDA or the sponsor relies on to establish that the tested product is effective; or a study in which a single investigator makes a significant contribution to the demonstration of safety FDA is particularly concerned with Phase II and III trials (efficacy) and bioequivalence studies where results obtained by a single investigator can have a profound statistical effect on trial outcome In general, large open-label studies conducted at multiple sites, treatment protocols, Phase I tolerance studies, pharmacokinetic studies, and most clinical pharmacology studies are not “covered” studies FDA Counsel.com

10. How FDA Addresses Questionable Financial Deals FDA may take "any action it deems necessary to ensure the reliability of the data, including": FDA itself auditing the data from that investigator; Requesting the applicant submit further analyses of data; e.g., to evaluate the effect of that investigator's data on the overall study data; and … FDA Counsel.com

11. How FDA Addresses Questionable Financial Deals … FDA may take "any action it deems necessary” … Requesting sponsor conduct additional independent studies to confirm the results of the questioned study; and Refusing to treat the covered clinical study as providing data that can be the basis for agency action (e.g., an application approval). FDA Counsel.com

12. Addressing Financial Disclosure Before FDA Does Clinical investigator selection process -- make compliance an integral aspect of selection find out early, before clinical protocols are set in stone; allows you to possibly address via study design to minimize bias if present, document per regulations FDA Counsel.com

13. Addressing Financial Disclosure Before FDA Does … Clinical study agreements should “mirror” the regulations – mandate disclosure of Interests or a certification there’s nothing to disclose a constant duty to update if there is any change FDA Counsel.com

14. Addressing Financial Disclosure Before FDA Does … include the right to obtain a one-year post study update regarding interests CRO agreements should obligate the CRO to obtain disclosure/ certification FDA Counsel.com

15. Minimizing Bias In Event of Financial Disclosure Key – take the action early; you will have to describe it later in your marketing application and you also may not be able to address effectively later FDA Counsel.com

16. Minimizing Bias In Event of Financial Disclosure … Possible angles: multiple study sites/investigators blinding objective endpoints randomized assignment of patients to treatment v. control groups have someone other than investigator measure subjective endpoints FDA Counsel.com

17. Other Considerations The Jesse Gelsinger scenario -- If an investigator has a significant financial interest, has that been adequately disclosed in the study’s informed consent documents?? Other entities may also impact financial disclosure duties, such as: the investigator’s institution (e.g., university or hospital) may have separate rules; HHS rules may apply as well (e.g., if federally funded). FDA Counsel.com

18. Questions? Call, e-mail, fax or write: Michael A. Swit, Esq. Law Offices of Michael A. Swit 539 Samuel Ct., Suite 229 Encinitas, California 92024 760-815-4762 ♦ 760-454-2979 (fax) mswit@fdacounsel.com http://www.fdacounsel.com FDA Counsel.com

19. About the speaker... Michael A. Swit has extensive experience in all aspects of FDA regulation with a particular emphasis on drugs and medical device regulation. In addition to his regulatory law experience, Mr. Swit also served for three and a half years as vice president and general counsel of Pharmaceutical Resources, Inc. (PRI) a prominent generic drug company and, thus, brings an industry and commercial perspective to his representation of FDA-regulated companies. While at PRI from 1990 to late 1993, Mr. Swit spearheaded the company’s defense of multiple grand jury investigations, other federal and state proceedings, and securities litigation stemming from the acts of prior management. Mr. Swit then served from 1994 to 1998 as CEO of Washington Business Information, Inc. (WBII) a premier publisher of FDA regulatory newsletters and other specialty information products for the FDA publishing company. Before starting FDACounsel.com, he was with Heller Ehrman from May 2001 to May 2003, and also twice in private practice with McKenna & Cuneo, from 1988 to 1990 and, most recently, from 1999 to 2001, first in that firm’s D.C. office and most recently, in its San Diego office. He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius from 1984 to 1988. Mr. Swit has taught and written on a wide variety of subjects relating to FDA law including, since 1989, co-directing a three-day intensive course on the generic drug approval process, serving on the Editorial Board of the Food & Drug Law Journal, and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved, published by WBII. Mr. Swit holds an A.B., magna cum laude, with high honors in history, in 1979, from Bowdoin College, and earned his law degree from Emory University in 1982. He is a member of the California, Virginia and District of Columbia bars. FDA Counsel.com