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For those conducting clinical trials, strict adherence to state regulatory requirements makes sound business sense.
The regulatory framework for conducting clinical trials in the United States is set forth under Title 21 of the Code of Federal Regulations, which addresses the protection of human subjects, institutional review boards (IRBs), and financial relationships, as well as other significant regulatory issues in the conduct of clinical trials. While Title 21 sets forth regulations that need to be complied with, the clinical trial professional must understand that there are specific state laws and regulations that impact clinical trials (e.g., those related to informed consent, age of consent, legal representatives, and government notification).1
Although it is important that clinical trial sponsors and investigators focus on complying with FDA regulations, these FDA regulations do not preclude states from imposing their own requirements.2 Clinical trial professionals must remember that FDA's informed consent regulation specifies that the states are not preempted from establishing additional requirements. Failure to comply with state laws and regulations in areas such as informed consent can expose sponsors and investigators to significant liability risks. Lawyers, who specialize in injury claims caused by medical treatment, are becoming particularly creative in their attempts to file suits against individuals and companies sponsoring and conducting clinical trials. Negligence, informed consent, battery, wrongful death, and conflicts of interest are state law theories utilized by plaintiffs' counsels to allege liability of parties conducting clinical trials.
Most recently, significant verdicts and settlements in favor of clinical trial participants over the last few years have contributed to the increase in clinical trial lawsuits.3 Various theories of tort liability may be brought on behalf of clinical trial participants, but it is important to understand that these causes of action typically involve both federal and state law-based claims. Compliance with state informed consent requirements (e.g., age and legal capacity of the clinical trial subject to consent) will significantly impact the ability of a plaintiff's counsel to raise these various theories of tort liability.
It is important for the clinical trial professional to understand that cases citing negligence based on a failure to provide informed consent, or inadequate informed consent, often depend on state interpretation. Failure to comply with state consent requirements can be used by a plaintiff's counsel to assert negligence-based claims, and in some jurisdictions may be used as evidence of negligence per se, which exposes the clinical trial professional to increased risks. Failure to adhere to state law requirements may cause clinical investigators to improperly give consent human subjects. Those who have the legal capacity to give consent on behalf of minors or incompetent patients, also may not properly obtain it. This increases exposure to lack of informed consent-based claims.
Traditionally, injured clinical trial subjects have brought claims against pharmaceutical manufacturers based on theories of products liability, negligence, and other legal causes of action. In recent years, however, an increasing number of cases have included claims against clinical trial investigators, professionals assisting investigators in conducting trials, and IRBs of the institutions where the trials are being conducted.
A widely-publicized case that raised awareness of clinical trial liability involved the death of a healthy teenager who had participated in a gene therapy experiment.4 The estate of the deceased teenager sued the physician, the founder of the sponsor company, the sponsor company, and the university trustees. The suit was filed in state court and alleged state claims that included wrongful death, intentional assault and battery, lack of informed consent, intentional and negligent infliction of emotional distress, common law fraud and misrepresentation, and products liability. Another lawsuit regarding this gene therapy trial subsequently was filed on behalf of another participant with similar allegations.5 The lawsuit involving the teenager ended in a multimillion dollar settlement; however, had it proceeded to trial, state statutes and regulations regarding informed consent would have been central to the plaintiff's case.
In another case involving injured clinical trial participants, which had theories of liability based upon state law, plaintiffs receiving intraocular lenses under clinical investigation sued the hospital where the trial was being conducted, the investigator performing the procedure, and the product manufacturer on theories of negligence based on lack of informed consent, failure to respond to product recalls, and medical battery.6 Likewise, in 2000, a U.S. District Court in Florida approved a consent decree entered into between a certified class of pregnant women participating in research at Tampa General Hospital and the hospital.7 The decree, among other things, mandated the establishment of a multimillion dollar settlement fund, the development and implementation of research protocols designed specifically to address research involving pregnant participants, and the use of informed consent forms readable by participants.8 Similarly, in 2001, minor clinical trial subjects in a research program involving lead paint dust levels sued the Kennedy Kreiger Institute, Inc. (a Johns Hopkins-related research facility) and the IRB where the trial was conducted.9
Plaintiffs' counsels have also recently targeted IRBs overseeing clinical trials. In 2002, a number of individuals who had participated in a melanoma research study sued multiple defendants involved in the study. Specifically, the plaintiffs who had participated in the study at the University of Oklahoma sued the university, the investigator, the sponsor, the associated medical centers, each IRB member individually, the dean of the university's Department of Medicine, and the Chair of the Department of Surgery.10 Although this particular suit was dismissed, the plaintiffs' law firm subsequently filed additional lawsuits naming similar defendants at other clinical sites across the country that were involved in conducting this trial.12
In another case involving clinical trials, a complaint was filed in the U.S. District Court for the Southern District of Ohio against the Board of Regents of Ohio State University, the Ohio State University Board of Trustees, and the Ohio State Medical Center as related to the conduct of a nerve regeneration clinical trial. A clinical trial participant who had undergone a nerve biopsy as part of the defendants' study allegedly suffered injuries and damages (including sensory deficits, foot pain, altered balance, emotional distress, loss of enjoyment of life, and extreme postsurgical pain). The theories of liability within the filed complaint included inadequate informed consent and violations of the right to be treated with dignity. In addition, the plaintiff brought state civil rights claims stemming from Ohio State University's involvement. The case is pending and ultimately will be litigated on whether state and federal law requirements regarding informed consent were met.
These above cases demonstrate that all participants in clinical trials are at risk of liability and that failure to be aware of all regulations that apply to clinical trials can increase this risk of liability. While sponsors and institutions overseeing clinical trials often are primary targets for lawsuits, individual investigators and associated parties should be aware of the critical importance of complying with federal and state regulations in an effort to ensure that they minimize potential exposure to liability. The clinical trial professional needs to be fully aware that individual states have an important role in determining whether a patient has properly consented to a clinical trial investigating experimental new therapies.
The following are some of the areas of clinical trial that are impacted by state laws.
A number of states have adopted informed consent standards in addition to FDA's informed consent requirements. Although many of these state standards are similar to FDA's regulations, some distinct important differences occasionally arise. For example, California clinical trial subjects, as part of the consenting process, must receive a copy of California's Experimental Subject's Bill of Rights.12
In addition, some states have created prohibitions against obtaining consent from individuals in mental health facilities except under certain circumstances.13 In some states it is specifically spelled out within state regulations as to who can consent for a patient with impaired cognitive function. In Montana, if a human subject is a resident of a mental health facility, the researcher must, at least ten days before the research is to begin, send a "notice of intent" to enroll the patient as a subject to the patient, the patient's next of kin, and the patient's legal guardian among others.14 Likewise, some states require court review and approval before a patient, unable to consent on their own behalf, is enrolled in an experimental clinical trial. Under some state laws, executed consent forms are effective only for a specific period of time.15
Therefore, clinical trial professionals must be aware of these time limits, and must be prepared to re-consent subjects who participate in studies that extend beyond the effective date of the informed consent.
In all states, state statutes specify the age at which individuals generally are able to consent to medical treatment.16 State law also controls requirements governing legal representation of minors and incompetent adults. Some states require the consent of both parents of a minor child, while other states only allow a custodial parent to consent to any such treatment. Many states allow emancipated minors to consent to their own medical treatment. The ability of these emancipated minors to consent may vary according to state statue and require as much as a court decree and as little as living apart from a parent or guardian for a period of time.17 These state regulated consenting requirements are crucial to any clinical trial's informed consent process because they will dictate whether consent obtained from certain classes of individuals is valid with or without representative participation. Additionally, some states such as Illinois require that adequate provision must be made for the voluntary assent of "minors who are capable" in research involving children and their families.18 Failure to comply with age of consent and legal representative requirements may result in invalid consent exposing sponsors, investigators, etc. to liability.
Many states have regulations for the conduct and make-up of IRBs. For example, Massachusetts requires IRBs to be made up of no fewer than five individuals from varying backgrounds, and to document the committee members' backgrounds.19 Additionally, some states require that IRBs evaluate specific issues prior to their approval of clinical trials. As an example, Florida requires, among other things, that IRBs specifically determine: that the subject population is appropriate in terms of characteristics and size; that subjects are recruited without coercion; that the potential benefits of the research are maximized; and that the form of consent is ethically sound.20 An IRB's failure to comply with state requirements may create risk to exposure of claims that could be based upon their approval of clinical trials, without having a proper IRB in place.
With the enactment of the Health Insurance Portability and Accountability Act (HIPPA), the clinical trial professional may wrongly assume that compliance with HIPPA addresses all privacy issues. Unfortunately, states continue to regulate patient medical data. The clinical trial professional must be aware that HIPPA standards do not preempt state medical privacy laws where the state law is more stringent. State privacy laws regarding various testing, such as genetic testing and HIV testing, need to be complied with if these tests are part of the study's protocol. Many states have specific counseling and consenting requirements involving these two areas of testing.
While state laws and regulations certainly impose additional requirements on clinical trial professionals, there are many state statutes and regulations that are beneficial to sponsors of clinical trials. Understanding various state laws can allow sponsors strategic insight as to where to conduct their clinical trials. Certain state laws contain provisions concerning particular therapeutic classes of experimental drugs. Many states feature provisions specifically related to cancer research and require that specific insurance coverage be provided to encourage trials involving cancer therapeutics. Further, many states offer various incentives for specific research related to serious public health diseases such as AIDS. Georgia, for example, allows for some cancer patients to use marijuana in a therapeutic research program.21
Because clinical trial professionals are increasingly becoming a target for plaintiffs' counsels, sponsors, investigators, IRBs, and institutions must ensure proper regulatory compliance for clinical trials. Compliance with federal FDA requirements should continue with great vigilance, but states' increasing involvement in this area means that no lesser effort should be devoted to ensuring that clinical trials comply with state requirements as well.
John Serio is senior counsel at Brown Rudnick Berlack Israels LLP, One Financial Center, Boston, MA 02111, 617.856.8238, firstname.lastname@example.org
1. See generally STATE-BY-STATE CLINICAL TRIAL REQUIREMENTS REFERENCE GUIDE (Barnett Int'l 2004) (John C. Serio, lead author).
2. 21 CFR § 50.25(c)
3. See generally Alice Dembner, Lawsuits Target Medical Research, B. GLOBE, Aug. 12, 2002,
4. See Gelsinger Complaint (2002), at http://www.sskrplaw.com/links/healthcare2.html (last visited Oct. 20, 2005).
5. See Aderman Complaint (2002), at http://www.sskrplaw.com/gene/aderman.html (last visited Oct. 20, 2005).
6. Kus v. Sherman Hospital, 644 N.E.2d 1214 (Ill. App. Ct. 1995).
7. 2000 WL 1682918 (M.D. Fla. 2000).
8. Id. at 3-4.
9. 782 A.2d 807 (Md. 2001).
10. Robertson v. McGee, 2002 WL 535045 (N.D. Okla. 2002).
11. David B. Resnik, Liability for Institutional Review Boards: From Regulation to Litigation, 25 J. LEG. MED. 131 (2004).
12. See CAL. HEALTH & SAFETY CODE § 24172 (West 2003).
13. See, e.g., DEL. CODE ANN. tit. 16, § 5172(b)(1) (2003).
14. Mont. Code Ann., § 53-21-147(2) (2003)
15. Wis. Adm. Code HFS 94.03(1)(f) (2003)
16. See, e.g., MASS. GEN. LAWS ch. 112, § 12f (2004) (establishing Massachusetts' age of consent as 18, and permitting minors who are married, parents (or pregnant), members of the armed forces, or who are emancipated to consent to medical treatment).
17. 22 M.R.S.A § 1503
18. Ill. Admin. Code Title 89 § 432.6
19. See, e.g., MASS. REGS. CODE tit.105, § 700.009 (2004).
20. See http://www.doh.state.fl.us (last visited August 10, 2005)
21. O.C.G.A. § § 360-12-.01-.05 (2003)
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