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For truly informed consent, methods should gauge a subject's real grasp of a clinical trial's complexities.
The concept of informed consent has evolved over the past century. More than just a document, informed consent (IC) has been acknowledged as a process. It conveys information to the potential subjects with—ideally—active discourse between the subject and principal investigator or designee in order to obtain the potential subject's agreement to participate in a clinical trial. But once the form is signed, indicating IC was obtained, can the study team truly assert that the subject has an adequate grasp of the complexities participation in a clinical trial entails?
Established by the enactment of the National Research Act in 1974 in response to the growing ethical concerns surrounding clinical trials, institutional review boards (IRBs) carefully review clinical trials to assure that the rights and welfare of human subjects are protected. As part of the review, the IRB examines consent forms to ensure that required elements are contained in explicit fashion, as dictated by Title 45 of the Code of Federal Regulations Part 46.1,2 Adequate explanations of study procedures and fair representation of risk and benefit must be reviewed and approved, plus the consent language must meet a level of readability—usually an eighth-grade reading level.
Approval of the form by the IRB is the first step to beginning the IC process. Although the regulatory references, including the ICH GCP guidelines, 45 CFR 46.117a and 21 CFR 50.27, state that an approved written consent form is required to indicate consent, the form does not represent the process nor does the process end with the subject's signature.3 Furthermore, 45 CFR 46.111(a) requires the IRBs to assure that the IC process is taking place in addition to providing adequate documentation. However, responsibility lies with each investigator.
Given then that the process is ongoing, how is the study team to ensure that the subject is fully informed? First, one must assess the document for adequacy both before and after IRB review. Is the consent form truly readable? According to Golec,
lengthy consent forms and low readability contribute to poor comprehension. Golec further postulates that IC forms containing recitation of innumerable risks, no matter how minute the incidence, can be as harmful as too little information. Additionally, pages and pages of pure text can be intimidating and overwhelming to the potential subject.
Moving beyond the form, it is incumbent upon the study team to evaluate IC practices. In the traditional setting, the subject is presented with a lengthy legal document to read. An oral explanation of the study procedures follows, along with, presumably, an active conversation with the potential subject to address concerns and to assess understanding. Naturally, presentation styles will vary from person to person and situational influences such as daily workload, the presenter's or the subject's mood that day, or language or cultural barriers can influence how the information is conveyed.4 The end result is that the presentation of the clinical trial is inconsistent and may be inadequate.
Next, subject attitudes and perceptions will influence the IC process. If your subject does not ask questions, does that signify full comprehension or utter confusion? Mark Hochhauser,5 a renowned readability consultant, contends that a significant factor in comprehension is "omission neglect," when a subject is unaware of what they do not know. Considering the technicality and complexity of medicine, it is not reasonable to expect the potential subject to be fully cognizant of either their medical condition or to fully understand the procedures that will be involved in the clinical trial. Potential subjects may be intimidated by the situation, may not want to risk embarrassment by asking for clarification or may simply think that participating will appease their doctor.4 All are attitudes and beliefs that lead to "uninformed consent." Conversely, refusal to participate does not indicate full understanding either. Regardless of the subject's decision, full comprehension must be assessed in some manner after the trial is explained to ensure that the subject is making an informed decision.
Several methods can be employed to foster understanding. Much has been written recently on the use of technology to complement the IC process. Educational materials including DVDs, brochures, and Web sites, all requiring IRB approval, can be used to supplement the informed consent form and assist in conveying complex ideas in a medium that may be more easily understood by the potential subject. In fact, the Office of the Inspector General issued a report in 2002 suggesting that clinical trial Web sites, with proper regulation, may be a promising tool to enhance the IC process.
Not all supplemental material must come from the sponsor. Academic institutions are taking on a more active role in educating the public. The University of North Carolina at Chapel Hill has published a brochure entitled "Should You Volunteer?" that is available in Spanish and English.
The brochure provides basic information about clinical trials in general and suggests questions that interested participants may elect to ask during the course of consenting. An accompanying video is also available that further discusses participating in clinical trials. Using multimedia to convey information may increase comprehension for those who have difficulty with the written word.
Accurately assessing a subject's grasp of the clinical trial may be difficult, but steps can be taken to ensure that a reasonable understanding is present. Quite often, the person obtaining the consent relies on verbal assurance from the subject; however, as stated previously, this may not reflect the actuality. Therefore, a brief post-test may reveal any misunderstandings. Subjects may be asked to describe the study procedures or answer simple open-ended questions that elicit a narrative response to evaluate comprehension. Documentation of the answers will provide verification that a truly informed consent was obtained. Alternatively, a trusted third party not related to the study team, like a clinic nurse, might question the potential subject to further assess understanding. Once again, documentation of the subject's response is recommended. It is important to remember that IRB approval must be obtained for any post-test questioning.
In May of 2000, amid a spate of highly publicized ethical violations in research, Health and Human Services Secretary Donna Shalala took clinical trial professionals—including leaders of universities and academic health centers—to task, emphasizing the responsibility they carry to ensure the protection of human participants in clinical trials.8 Ultimately, it is the responsibility of the principal investigator to ensure fully informed consent exists, despite the fact that a designee may have obtained the IC. It is incumbent upon all study staff to take whatever measures are necessary to ensure that the informed consent form represents true understanding and not just a signed form.
1. Code of Federal Regulations, Title 45, Part 46 Protection of Human Subjects. U.S. Government Printing Office, Washington, DC.
2. Food and Drug Administration. Information sheet: Guidance for Institutional Review Boards and Clinical Investigators 1998 update. A Guide to Informed Consent (FDA, Rockville, MD, 1998).
3. L. Golec, "Are You Truly Informed about Informed Consent?" The Monitor, 18 (3) 15–23 (Fall 2004).
4. J.S. Brady, "Multimedia Delivery Can Enhance the Consent Process," Applied Clinical Trials, 12 (1) 36–42 (January 2003).
5. M. Hochhauser, "Subject Recruitment and Informed Consent," Applied Clinical Trials–Subject Recruitment Supplement, 12 (11) 10–13 (2003).
6. Department of Health and Human Services, Office of Inspector General, "Clinical Trial Websites: A Promising Tool to Foster Informed Consent," (DHHS, Washington, DC, May, 2002). Retrieved September 21, 2004, from http://oig.hhs.gov/oei/reports/oei-01-97-00198.pdf).
7. Office of Human Research Ethics. "Should You Volunteer?" (University of North Carolina at Chapel Hill, Chapel Hill, NC, 2004).
8. HHS News, "Secretary Shalala Bolsters Protections for Human Research Subjects" (DHHS, Washington, DC, 23 May 2000).
Tammi Jaynes, RN, CCRC, is a global training specialist with INC Research, Raleigh, NC, email: firstname.lastname@example.org. Prior to joining INC Research, she was project manager in the Office of Clinical Trials at the University of North Carolina at Chapel Hill.