State Regulation of Clinical Trials

Society for Quality AssuranceAnnual Meeting

Washington, D.C.October 16, 2003

Michael A. Swit, Esq.Michael A. Swit, Esq.

Law Offices of Michael A. Switmswit@fdacounsel.comFDACounsel.com

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FEDERALISM – Or Why State Laws Matter

U.S. Constitutional legal system – The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people. (10th Amendment)

States – broad powers – to “police” conduct, particularly on health issues

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Why State Laws Matter …

But, if FDA, HHS, etc., already regulate clinical studies, why can’t we just follow the federal rules?

“Preemption” – where federal and state law coexist, it is possible that federal law will “preempt” – or trump – state law.

But, not always …

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FEDERAL PREEMPTION – When Does Uncle Sam Win? Not all time!! In some cases, preemption may

be explicit under the federal statute – see medical device laws

In other cases, if not explicit, the federal scheme

must completely occupy the “field” to preempt; or

If irreconcilable conflict between federal and state; or

Using state standard would frustrate the goals of the federal law

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PREEMPTION – Supreme Court Cases No case in the clinical research arena;

however, guidance exists in other cases, including FDA-related

Silkwood v. Kerr-McGee – 1984 company claimed punitive damages awarded

preempted by federal laws on nuclear handling Supreme Court – explicit preemption under Atomic

Energy Act did not extend to state punitive damages awards in a claim relating to nuclear safety

Medtronic v. Lohr – 1996 -- Supreme Ct. ruled state tort law claims not preempted by FDA 510(k) device clearance process

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PREEMPTION – Supreme Court Cases … Buckman – 2001 – Supreme Ct. rules FDA’s more detailed premarket

approval process did preempt certain state tort claims

Courts did not fully decide the question of whether general state tort duties were preempted by the MDA; some language suggests they would.

NOTE: the medical device cases rely on a specific provision of device statutes – 21 USC §360k(a) – that precludes a state from establishing (or continuing) a requirement that differs or adds to those in the Medical Device Amendments (“MDA”) of 1976.

No such explicit statutory provision vis-a-vis federal clinical research law. Thus, assume that the courts would not regard the federal scheme as so pervasively regulating as to preempt.

Courts -- might not set aside on preemption basis state laws on clinical research – if they set forth more detailed requirements – reluctance to relax standards of care relative to patient safety

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WHICH STATES ARE MOST ACTIVE IN CLINICAL RESEARCH?

Population Rank1 # Clinical Studies Rank2

1 California Maryland (19)

2 Texas New York

3 New York California

4 Florida Texas

5 Illinois Pennsylvania

6 Pennsylvania Ohio

7 Ohio Washington (15)

8 Michigan (13) Illinois

9 New Jersey (20) Florida

10 Georgia (19) Massachusetts (13)

11 North Carolina North Carolina

12 Virginia (18) Missouri (17)

1. http://www.census.gov/population/cen2000/tab04.txt2. Compiled from http://www.clinicaltrials.gov Note: # in parens is rank

in other column.

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HOW CAN WE KNOW ALL THE STATES’ LAWS?

You can’t (easily) One general source: ClinLawSM

http://www.clinlaw.com – overview of state requirements with citations (but, lacks full text)

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

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California v. Texas -- Age of Consent

California Texas

Majority – 18Mental Health Care – 12

Medical Care – 15 or living apart from parents

Majority – 18, unless disabilities of minority

removedMental Health Care &

Medical Care – 18, unless 16 and independent, then can consent to:♦ infectious disease

treatment♦ pregnancy treatment (but not an abortion)♦ substance abuse

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Consent Process …

California TexasWritten 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

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Consent Process

California TexasInformed 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.

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Consent Process …specifics needed

California TexasMust:

♦ 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.

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Consent Process …

California Texas

♦ 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

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Consent Process …specifics needed

California Texas

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

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LEGALLY AUTHORIZED REPRESENTATIVE

California TexasPriority 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 childre

♦ 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

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LEGALLY AUTHORIZED REPRESENTATIVE

California TexasIf 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

Not addressed specifically

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IRBSCalifornia Texas

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)

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RECORDS REQUIREMENTS

California Texas

♦ 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

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RECORDS REQUIREMENTS

California Texas

♦ 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

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RECORDS REQUIREMENTS

California Texas

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.

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STATE I.N.D. RULES

California TexasNone 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

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EMERGENCY EXPERIMENTATION

California Texas

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.

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STUDIES ON MENTALLY ILL OR DEVELOPMENTALLY

DISABLED

California Texas♦ 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)

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MENTALLY ILL OR DEVELOP-MENTALLY DISABLED …

California TexasNo 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

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Research on Prisoners

California TexasInmates 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.

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PRACTICAL CONSIDERATIONS

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)

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PRACTICAL CONSIDERATIONS … 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

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Questions?

Michael A. SwitAttorney at Law

Law Offices of Michael A. Swit539 Samuel Ct. , Suite 229 ♦ Encinitas, CA 92024

Office: 760-815-4762 ♦ O-Fax: 760-454-2979mswit@fdacounsel.com

Also Admitted In Virginia and D.C..

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About your presenter …

Michael A. Swit has over 19 years of experience addressing critical FDA legal and regulatory issues. His vast and varied experience, which he is now providing as a solo practitioner, includes serving 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-regulated community. From May 2001 to to May 2002, Mr. Swit was special counsel in the FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe. Before that, he was 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 and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. He is a member of the California, Virginia and District of Columbia bars.

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