1. State Regulation of Clinical Trials 5th National Conference on Managing Legal Risks in Structuring and Conducting Clinical Trials American Conference Institute Boston September 27, 2006 Michael A. Swit, Esq. Vice President, Life Sciences

2. 2 MOST ACTIVE CLINICAL RESEARCH STATES Top 12 States -- Population 1 Top 12 States -- Most Clinical Studies 2 1 CaliforniaMaryland (19) 2 TexasNew York 3 California 4 FloridaTexas 5 IllinoisPennsylvania 6 Ohio 7 Washington (15) 8 Michigan (13)Illinois 9 New Jersey (20)Florida 10 Georgia (19)Massachusetts (13) 11 North Carolina 12 Virginia (18)Missouri (17) 1.http://www.census.gov/population/cen2000/tab04.txthttp://www.census.gov/population/cen2000/tab04.txt 2.Compiled from http://www.clinicaltrials.gov Note: # in parens is rank in other column.http://www.clinicaltrials.gov

3. 3 HOW CAN WE KNOW ALL THE STATES’ LAWS? You can’t (easily) –One general source: State-by-State Clinical Trial Requirements Reference Guide, Sept. 2004, Serio, et al., Editors, Barnett Educational Services Focus on key states -- e.g., see our chart Work with your IRBs – they are required to know local conditions under federal law – thus, protocols and consents should be tailored by them to meet local rules

4. 4 California v. Texas -- Age of Consent CaliforniaTexas Majority – 18 Mental Health Care – 12 Medical Care – 15 or living apart from parents Majority – 18, unless disabilities of minority removed Mental Health Care & Medical Care – 18, unless 16 and independent, then can consent to: ♦ infectious disease treatment ♦ pregnancy treatment (but not an abortion) ♦ substance abuse

5. 5 Consent Process … CaliforniaTexas Written consent required prior to administering an experimental drug (H&S 111525) No similar explicit rule on experimental drugs. But, separate law that hospital patients have right to be informed of experimental or research projects affecting their treatment

6. 6 Consent Process... CaliforniaTexas Informed consent must include all pertinent info, including financial (Moore v. Regents) Experimental Subjects “Bill of Rights” – must be provided to subject and signed before consent to research H&S § 24172. No similar explicit rule on financial disclosure; but, after Gelsinger, little question is an implied obligation to consent process. Not specifically addressed.

7. 7 Consent Process … specifics needed CaliforniaTexas Must: ♦ Sign ♦ Date ♦ Witness ♦ State purpose ♦ State any placebo use ♦ Risks & benefits ♦ Alternatives ♦Recovery time ♦ Withdrawal rights ♦ Name & institution doing study ♦ Sponsor or funding source ♦ Name & address of impartial third-party contact to complain to Detailed requirements not specifically addressed in detail.

8. 8 Consent Process … CaliforniaTexas ♦ Minors – need parental consent; & assent of children seven+ years old Minors – if parent, not available, others can (e.g., grandparents) per Tex. Family Code § 32.001 Old law – minor assent to mental health treatment required; repealed in 2001

9. 9 Consent Process … specifics needed CaliforniaTexas Consent relative to Research on Mentally Ill: ♦ If at state hospitals, more requirements apply: confidentiality statement contact info. For questions, costs & future findings ♦ To review confidential records of developmentally disabled person, researcher must obtain informed consent of subject or LAR ♦ Short form consent is possible (17 CCR 50429) ♦ IRB can authorize waiver of consent in certain limited circumstances (17 CCR 50427) Consent relative to Research on Mentally Ill (25 TAC 414.758) – must meet 45 CFR § 46 requirements, plus: ♦ must include any extension of length of stay at facility ♦ ability to get research drug or device after research over ♦ use of placebo ♦ if research involves using test article known to be ineffective for targeted pop. ♦ risk of deterioration ♦ greater requirements if research involves more than minimal risk: independent professional must assess capacity of individual to consent ♦ consent “must be assessed and enhanced throughout” the research

10. 10 LEGALLY AUTHORIZED REPRESENTATIVE CaliforniaTexas Priority Order: (H&S 24178) ♦ Agent via a health care directive ♦ conservator or guardian ♦ spouse ♦ adult child ♦ custodial parent ♦ adult sibling ♦ adult grandchild ♦ closest available adult kin Note: if two or more of same priority, if any objects, NO CONSENT Note: different order for emergency room use Priority order: (H&S § 313.004) ♦ Spouse ♦ Adult child of patient w/waiver & consent of all other adult children ♦ Majority of reasonably available adult children ♦ Parents ♦ Person last ID’d by patient prior to incapacity ♦ Nearest living relative ♦ Member of clergy Note: majority rules if more than one

11. 11 LEGALLY AUTHORIZED REPRESENTATIVE CaliforniaTexas If LAR involved, informed consent for research can only be for research related to the health of the subject (H&S § 24175) If subject has previously appointed a health care power of attorney, can appoint a “surrogate” by personally informing the supervising health care provider. If so, surrogate controls over POA. (H&S § 24175). Not addressed specifically

12. 12 IRBS CaliforniaTexas State Dept. of Health Services must “accept” the IRB; however, if you’re under a federal assurance, you’re deemed accepted (H&S § 111540) Studies on Developmentally Disabled: IRB must meet 17 CCR 50401: ♦ 5 members 1 lay member 1 member focused on rights of subjects 1 member not affiliated w/facility ♦ Must review protocols within 31 days of receipt Not specifically addressed; but see below Studies on Developmentally Disabled: IRB must meet 25 TAC 414.755(d): ♦ 3 members must know the mental disorders: one professional 2 must have been mentally ill or retarded, or a family member of such, or an advocate ♦ Facility IRB must be approved by Texas Dept. of Mental Health’s Office of Research Admin. (ORA)

13. 13 RECORDS REQUIREMENTS CaliforniaTexas ♦ Illegal to disclose medical information unless compelled by court, law enforcement agency or patient. ♦ Disclosure is OK to a P.I. or research organization for research purposes if patient ID protected ♦ Similar ♦ Similar, but also, Covered Entity must: document consent document waiver OK’d by an IRB or privacy board, that says: ◘ use of PHI is minimal risk to person ◘ privacy rights will not be adversely affected ◘ privacy risks are reasonable relative to anticipated research benefits ◘ adequate plan to keep identifiers from being improperly used ◘ plan to destroy identifiers later ◘ written assurances PHI will not be reused or disclosed

14. 14 RECORDS REQUIREMENTS CaliforniaTexas ♦ Records release forms must be at least 8 point type and include: specific uses name of provider name of info recipient expiry date ♦ Disclosure of lab results via electronic means is barred ♦ Federal HIPAA overrides state law (H&S § 130311, as of 9/02) Similar rule – Occupations Code § 159.005(b); consent must specify: records to be released reasons for release recipient Not specifically addressed ♦ HIPAA rules essentially apply (H&S § 181.101

15. 15 RECORDS REQUIREMENTS CaliforniaTexas Pharmaceutical companies (but not medical device firms) barred: ♦ from disclosing medical information about a patient without consent. ♦ conditioning receipt of drugs on patient waiving those rights, except vis-à-vis enrollment in a clinical study Developmentally disabled research: ♦ to get access, researcher must sign confidentiality pledge per 17 CCR 50421 Not specifically addressed Not specifically addressed in this detail.

16. 16 STATE IND RULES CaliforniaTexas None explicit. BUT, cancer research – if not under a federal IND, must meet several requirements under H&S § 109325, including a written statement filed with state None explicit. BUT, to use approved drug for research, sponsor must submit a copy of FDA approval letter to Texas Commissioner of Health

17. 17 EMERGENCY EXPERIMENTATION CaliforniaTexas Need for consent for experimental treatment is exempted if a life- threatening situation (assumes incapacity to consent) Not addressed specifically, except a psychoactive drug can be administered without consent to a resident who is having a medication-related emergency.

18. 18 MENTALLY ILL OR DEVELOPMENTALLY DISABLED STUDIES CaliforniaTexas ♦ Executive director of state hospital also must OK research ♦ Other Detailed Requirements: researcher duties (17 CCR 50413) IRB SAME – 25 TAC 414.754(k) Detailed requirements (25 TAC 414.751 et seq.) ♦ adopts Belmont Report ♦ must be a court order for mental health services in effect before can approach individual in protective custody on being involved in research (25 TAC 414.754(f)

19. 19 MENTALLY ILL OR DEVELOP- MENTALLY DISABLED … CaliforniaTexas No similar requirement relative to involuntary commitment, but I.C. rules in H&S § 24170 are similar. If involuntarily committed: ♦ no placebos ♦ no ineffective doses or medications ♦ if prior studies with 100 or fewer patients have found minimal or no proof of safety & effectiveness

20. 20 Research on Prisoners CaliforniaTexas Inmates have right to choose; I.C. must include all (from prior slide), and: ♦ right to withdraw ♦ remuneration NOTE: only applies to behavioral research Penal Code § 3502 – bars biomedical research on prisoners Not addressed specifically.

21. 21 PRACTICAL ADVICE Retain clinical investigators with sophistication in clinical research; much of state law relates to practice of medicine Start early – requirements are detailed FDA (arguably) can cite you for missing a state requirement – will cite a federal violation (e.g., failure to monitor; inadequate consent; IRB not observing local conditions)

22. 22 PRACTICAL ADVICE … If using a CRO, consider those that have local offices in states you have clinical When in doubt, get local counsel!! Disclaimer: I am not admitted in Texas

23. The End

24. 24 About the speaker … Michael A. Swit, Esq., who is Vice President, Life Sciences at THE WEINBERG GROUP INC., has extensive experience in all aspects of FDA regulation with a particular emphasis on drugs and medical device regulation. In addition to his private legal and consulting 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 joining THE WEINBERG GROUP, he served in the FDA Regulatory Law Practices at both Heller Ehrman and McKenna & Cuneo, first in that firm’s D.C. office and then 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.

25. 25 Call, e-mail, fax or write: Michael A. Swit, Esq. Vice President, Life Sciences THE WEINBERG GROUP INC. 336 North Coast Hwy. 101 Suite C Encinitas, CA 92024 Phone 760.633.3343 Fax 760.633.3501 Cell 760.815.4762 D.C. Office 202.730.4123 michael.swit@weinberggroup.com www.weinberggroup.com Questions?

26. 26 For more than twenty years, leading companies have depended on THE WEINBERG GROUP when their products are at risk. Our technical, scientific and regulatory experts deliver the crucial results that get products to market and keep them there. Washington, D.C. ♦ San Francisco ♦ Brussels