Some Exceptions to Informed Consent
Madeleine M. Jester, RN, JD

Abstract

Generally, no investigator may involve a human subject in research regulated by the federal government unless that subject or the subject's legal representative has given informed consent. The Food, Drug and Cosmetic Act requires that investigators obtain this consent except where it is not feasible, or in the investigator's judgement, contrary to the best interests of the study subject.

This article discusses three situations in which there has been a deviation from the normal procedures usually followed in obtaining informed consent to the use of investigational test articles. One is a wartime scenario, one involves patients who present for emergency treatment and are unable to give consent for themselves, and one involves enrolling children in clinical studies. In situations such as these narrow exceptions to the normal requirements, it is extremely important to be aware of the rights of potential study subjects to be protected from unnecessary risks.

The FDA Grants a Wartime Exemption

During the recent gulf war, the Department of Defense(DOD) believed military personnel serving in the gulf region could be exposed to chemical or biological weapons. Given this belief, the DOD requested an exemption from the FDA to use certain investigational products that were thought to be the best preventive or therapeutic treatment for this exposure. The exemption was requested for certain battlefield situations where it would not be possible to obtain consent. Subsequently, the FDA published an interim regulation allowing a waiver to be granted from the requirement to obtain consent in situations that would facilitate accomplishing the military mission, where using the drugs would preserve the health of the recipient and the safety of other personnel, and where no other satisfactory alternative therapy was available.¹

The FDA agreed with the DOD's judgment that obtaining consent from military personnel would not be possible and withholding treatment would be contrary to the best interests of the personnel involved. This was a narrow expansion of the circumstances under which the FDA Commissioner may determine that informed consent is not feasible.²

Two experimental drugs were given to combat troops during Operation Desert Storm under this waiver. There was tremendous dissatisfaction with the handling of this situation on the part of military personnel, who felt that they received inadequate information about the possible side effects of the investigational drugs they were given.³ The Presidential Advisory Committee on Gulf War Veterans' Illnesses' final report recommended that if the interim rule granting the waiver were to be made final, certain areas would have to be addressed. These included adequacy of disclosure to service personnel and of recordkeeping, long term follow-up of drug recipients, review by an independent IRB, and additional procedures to enhance understanding, oversight and accountability.⁴ The situation served to emphasize the problems that can result when normal procedures for obtaining consent are not followed. Because of this the FDA requested comments from the public in the fall of 1997 (the comment period closed October 29,1997) as to whether or not this interim regulation should be modified or repealed.

Enrolling Children in Clinical Studies

Children may be vulnerable and subject to undue influence. The regulations regarding participation in clinical studies do not specifically mention children as a group from whom consent must be obtained. The regulations only require consent to be obtained from the study subject or legally authorized representative. However, obtaining consent from children before using them in clinical trials can help minimize your risk exposures. The FDA suggests, but does not require, that the institutional review boards (IRBs) reviewing research studies and consent forms consider requiring the approval of older children before they are enrolled in clinical studies. Some IRBs already require that two consents be signed, one for the parent or guardian, and one, written in simplified language, for children who possess the emotional and intellectual maturity to understand the concepts involved.⁵

The FDA Modernization Act signed into law on November 21, 1997, will present some new challenges in this area, since the Act provides an additional six months of market exclusivity for companies doing additional studies on use of their drugs in pediatric patients.⁶ This law may heighten companies' awareness of the rights of pediatric patients participating in clinical trials.

Research on Subjects With Life-Threatening Conditions

In October of 1996, the FDA amended its current informed consent regulations to facilitate emergency care research. The amended regulation permits certain clinical studies to be conducted that would involve subjects confronted by life-threatening situations rendering them unable to give informed consent. In these studies, the subjects would have access to life-saving therapies used in emergency situations.

Use of this exception to the normal process of informed consent must meet certain requirements. According to the regulations, the human subject must be confronted by a life-threatening situation in which there is no other comparable treatment available likely to save the subject's life. Also, there must be no way to obtain legally informed consent from the subject or timely consent from the subject's legal representative. Within 5 days of use of the test article a physician not involved with the clinical trial must review the clinical investigator's decision to use the test article, and documentation must be submitted to the IRB. Additionally, the new rule requires that the community where the research is being done be consulted and given information about the scope of the research.⁷

Since these new regulations were issued last year, two clinical trials have been successfully started using this exception. One is studying the use of an oxygen-carrying drug in the treatment of patients with hemorrhagic shock, and the other is testing a device for managing cardiac arrest.⁸

Generally, although this exception to the requirement for informed consent seems to be working reasonably well, there are some areas of ambiguity that could be problematic. The regulation does not make clear what constitutes adequate community consultation and disclosure, nor does it detail what procedures would be considered sufficient in trying to locate a representative of the patient who can give consent. In response to these concerns, the FDA will be issuing a guidance document in the future that should help to resolve some of these ambiguities.⁹

Conclusion

The situations described above are narrow exceptions to the normal requirements for obtaining informed consent. To be protected from unnecessary risk exposures, it is extremely important for investigators to remember that waiving these requirements is usually allowed only in situations where obtaining consent is not feasible, or is contrary to the subject's best interest. Investigators must proceed very carefully when deviating from the standard procedures for obtaining informed consent, to protect potential study subjects from unnecessary risks.

See also The Basic Requirements of Informed Consent, A History of Informed Consent, A Case Study on Informed Consent

References

1. Federal Register, Vol. 55 No. 246 Friday, December 21, 1990, Rules and Regulations p 52816, amending 21 CFR part 50, Protection of Human Subjects

2. Id., p 52815

3. 21 CFR Part 50, Docket No. 90N - 0302, Accessibility to New Drugs for Use in Military and Civilian Exigencies When Traditional Human Efficacy Studies Are Not Feasible; Determination Under the Interim Rule That Informed Consent Is Not Feasible for Military Exigencies; Request for Comments, Federal Register at http://www.fda.gov

4. Id.

5. FDA Document, Frequently Asked Questions, II. Informed Consent Regulations, p7, internet at http://www.fda.gov

6. FDA Modernization Act of 1997, section 505A(a)

7. 21 CFR Part 50, section 50.23

8. Marwick, Assessment of Exception to Informed Consent, Journal of the American Medical Association, November 5, 1997 Vol 278, No. 17 p 1393

9. Id.

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