Contrary to the stated purpose of helping patients make educated decisions concerning research participation, informed consent forms contain provisions that actually hinder clinical trial enrollment, according to findings published online January 12, 2010, ahead of print in Circulation: Cardiovascular Quality and Outcomes.
Researchers led by Kevin P. Weinfurt, PhD, of the Duke Clinical Research Institute (Durham, NC), surveyed 470 CAD patients to elicit their reactions to an informed consent document for a hypothetical cardiovascular medication trial, which was adapted from a previously approved trial at Duke University Medical Center. Interviewers reviewed the consent forms with study participants, all of whom were made aware that the clinical trial was hypothetical.
Comments Indicate Willingness to Participate
Overall, the study subjects made negative (152; 32.6%) comments far more frequently than positive (24; 5.1%) comments concerning different portions of the document, which included:
The area that received the most negative comments was the section regarding financial disclosure (15.8%), followed by patient rights (11.1%), confidentiality (9.8%), risks (8.7%), study purpose/protocol (5.7%), and benefits (4.3%).
Positive comments were most frequently made about the benefits (3.0%) and financial disclosure (2.1%) areas.
On a scale of 1 (“I definitely would not participate”) to 5 (“I definitely would participate”), patients who made at least 1 negative comment had a lower willingness to participate in the hypothetical trial (mean 2.86; SD 1.34) compared with those who did not make any negative comments (mean 3.52; SD 1.21; P < 0.001).
In particular, subjects who expressed at least 1 negative reaction to the patient rights, financial disclosure, or confidentiality portions of the consent form were more likely to “probably” or “definitely” not participate in the hypothetical trial compared with subjects who did not make negative comments about those sections (table 1).
Table 1. Likelihood of Choosing ‘Probably’ or ‘Definitely’ Not to Participate
≥ 1 Negative Comment
No Negative Comment
Subjects making negative comments regarding financial disclosure expressed aversion to the investigator’s financial relationships or thought the researcher might be biased by these arrangements. In terms of patient rights, subjects made negative comments regarding the lack of compensation or free medical care in case of a trial-related injury. Patients also expressed concerns regarding confidentiality and who would have access to their health information, because there was not an absolute guarantee of keeping patient information confidential.
In the study, those subjects who made negative comments were more likely to be older (P = 0.02), to have a higher education level (P = 0.04), to have previously participated in a research study (P = 0.05), and to be less trusting of research (P = 0.004).
Questions Not Very Telling
Contrary to negative comments, questions for clarification or further information expressed by the subjects had little predictive value. A total of 275 patients (58.5%) asked at least 1 question.
The area that generated the most questions (32.8%) was the study purpose/protocol section of the consent form, followed by confidentiality (19.4%), patient rights (18.7%), financial disclosure (15.8%), risks (14.7%), and benefits (9.8%). There was no association between asking a question about a particular section and willingness to participate in the hypothetical trial.
The researchers concluded that identifying particular areas of concern in the informed consent process “may help investigators design clinical research trials and model language in a way that reduces concerns or increases participant understanding, thereby enhancing informed consent for research.”
No Easy Fix
In an e-mail communication with TCTMD, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), indicated that the study pinpoints a key problem with the current practice of clinical research.
“The whole consent process is a real issue, and it is our observation that it is getting progressively more difficult to enroll patients in clinical trials,” he said.
Dr. Kirtane added that there is no easy solution. “The whole consent/enrollment process needs to be transparent, but there is often a fundamental information gap between a patient’s understanding of a clinical situation and how he/she is being treated. This only gets more confusing when a research study is involved,” he said. “It is often unrealistic to expect a patient who is coming in to be treated for a medical condition to understand the nuances of a 5-plus page consent form, but the information in the form is often very important for patients to consider when deciding whether to enroll or not.”
Blaming the Lawyers
In a telephone interview with TCTMD, Deepak L. Bhatt, MD, MPH, of the Brigham and Women’s Hospital (Boston, MA), noted that many of the problems with informed consent documents stem from legal considerations.
“The reality is that most of the informed consent documents out there are more legal documents than anything else,” he said. “I think that the primary purpose they serve in the minds of the lawyers who are largely involved with writing them is preventing or being able to argue against any potential litigation that might come up down the road. It’s unfortunate, but it’s felt to be necessary, and so many times the document fails its primary purpose, which is making sure the patient walks away feeling informed.”
Dr. Bhatt gave an example of an informed consent document with a provision stating that funeral costs would not be covered by the clinical trial. “I can understand if some lawyer thought, ‘If a patient dies in this trial, their family might sue for funeral costs,’” he said. “But really, any normal human being reads that and they’re going to think thrice about enrolling in that clinical trial even if it’s the most benign intervention possible.”
The Death of Clinical Research
But aside from using more common sense and having less hypersensitivity to litigation, making the informed consent process more useful on a nationwide basis requires a broader approach. “It would require a much more fundamental examination of how we do research in this country,” Dr. Bhatt said. “I think it would really involve bringing together different groups—academic research organizations, institutional review boards, NIH, FDA—to decide what the core elements are for the informed consent process and what sort of things could be jettisoned. There should also be some sort of legal immunity for whoever is involved in research—whether it’s investigators, contract research organizations, sponsoring companies, the government—such that they aren’t responsible for any funeral costs, for example, or if they are supposed to be, it’s spelled out, although I know that’s an absurd example.”
The consequences of not addressing this issue, Dr. Bhatt warned, are dire. “Informed consent is certainly part of what is hindering us from enrolling patients in clinical trials in the United States, and the direct consequence will be that clinical research will die in this country. In fact, it’s already died in some areas,” he said, stressing the importance of “trying to streamline the informed consent process in a way that respects patients’ rights and protects patients in terms of clinical research participation but also creates a system that isn’t so onerous for the investigator, sponsors, or whoever is involved with the research machine. I think everybody would win if that were to happen.”