Improving quality of informed consent in clinical research.

Informed consent is a vital ethical and regulatory requirement for the conduct of clinical research and is one of the most important benchmarks of ethical clinical research.[1] The process of informed consent requires that the clinical research participant voluntarily confirm his or her willingness to participate in a clinical trial. Several concepts are vital in obtaining valid informed consent: Disclosure, understanding, capacity, and voluntariness.[2] Disclosure means that the research participants are given all relevant information accurately about the nature, purpose, methods, risks, potential benefits, and alternatives available. Understanding denotes the research participants’ ability to comprehend the information provided and its relevance to their personal clinical situation. Capacity means a participant's ability to make decisions after understanding the information provided. Voluntariness denotes that a research participant's decision to participate in clinical research is made without coercion. The quality of informed consent depends on the type and amount of information disclosed, adequate capacity and understanding of information, and a voluntary decision to participate in a clinical trial.[23] Many potential research participants in developing countries are of low socioeconomic status, do not have adequate formal education, and have limited access to medical care. Hence, it is commonly assumed that it would be more difficult for them to comprehend study information and provide voluntary informed consent than for research participants from developed countries.[3] However, the question is: Is there any evidence to support the assumption that quality of informed consent from participants from developing countries is worse than the quality of informed consent from participants in developed countries?

In this issue of the journal, Thaker et al.[4] in a study have assessed the number of consent refusals in 10 clinical research studies to evaluate the quality of the informed consent process. Four studies (two interventional and two observational) had no consent refusals. In the remaining six studies (five interventional and one observational), the overall consent refusal rate was 23.8% among 680 patient participants and 14.9% among 296 healthy volunteers. The consent refusal rate was higher in interventional studies than in observational studies, and in pharmaceutical industry-sponsored studies compared to investigator-initiated studies. The authors ranked the studies relative to one another on a risk scale with 1 representing minimal risk and 10 representing the highest risk, using their own classification based on available knowledge of the intervention being studied, published literature on the intervention, and the patients’ disease condition. The consent refusal rate was 33.6% in seven more-than-minimal–risk studies and 7.5% in three no-more-than-minimal–risk studies with greater risk.

The relationship between the risk profile of clinical research studies and the consent refusal rate could help the clinical researcher in planning, screening and enrolment of study participants. However, the consent refusal rate by itself cannot serve as a metric of quality of consent unless we know why the patients refused consent. The study revealed that the most common reasons for consent refusals were unwillingness to undergo hospital admission, multiple blood collections, inability to comply with the study protocol, and the risks involved. However, out of 976 subjects, only a small number [40 participants (4.1%)] declined participation because of the likely risks of the study. Did the remaining 96% of subject really understand the risks? In addition, in the studies that had no consent refusals, did the participants consent having understood the risks or because they did not understand the risks? The authors of the present audit were limited by the retrospective nature of the study, and these questions can be answered only if studies of the quality of informed consent review the whole process of consent prospectively, focusing on addressing all elements.

Mandava et al. studied the quality of informed consent by reviewing 49 published studies (31 from developed countries and 18 from developing countries) that assessed participant comprehension and voluntariness.[3] They included studies that assessed at least one of two domains critical to measuring the quality of informed consent: Comprehension of study information and voluntariness of consent. The study found that comprehension of study information varied among clinical trial subjects in both developed and developing countries and that comprehension of randomization and placebo-controlled designs was generally lower than comprehension of other aspects of a clinical trial. For the trial participants, there were different sources of pressure to enlist in a trial. The participants from developing countries were less likely than those from developed countries to say that they could refuse to join or withdraw from a trial and were more likely to be concerned about the consequences of refusal or withdrawal.[3] One of the worries of the participants from developing countries was decreased access to health care. Mandava et al. stated that innovative strategies are required to facilitate improvement in the quality of informed consent.[3] This would need understanding of each patient's perception about clinical trials and informed consent.

The European Patients’ Academy on Therapeutic Innovation (EUPATI) survey of 6931 members of the European public showed that 84% had no or less than good knowledge of medicine research and development (R&D), and 78% had no or less than good knowledge of clinical trials.[5] According to a Center for Information and Study on Clinical Research Participation (CISCRP) global survey, among Asia Pacific respondents 29% reported that they did not understand or were unsure about what clinical research meant, 69% felt that informed consent forms were somewhat difficult or very difficult to understand, and only 25% were very willing to participate in a clinical research study.[5] In a study in Bangalore, the respondents perceived that signing the consent meant waiving of the participant's right to prosecute and that consent gave more protection to the doctor/researcher and hospital than to the participant.[6] Lack of awareness of clinical research would make the participant vulnerable and would impact the quality and effectiveness of the informed consent process. Hence, creating awareness and providing education about clinical research is vital to support patients in making informed decisions.

It would be desirable to emulate EUPATI, a European consortium of patient organizations, academic institutions, and pharmaceutical companies.[5] EUPATI aims to increase public knowledge and understanding of medicine R&D by developing a training course, a toolkit, and an online library of medicine R&D information for the public. To improve and ensure public trust in research, there is a need for greater transparency, honesty, and disclosure on the part of the researcher/doctor and a need for better monitoring of research.[7] The government should support such efforts and actively communicate to the public about the clinical research process, its value in improving public health, and regulatory measures for human subject protection and compliance enforcement actions.[8] The clinical research investigator and the sponsor should focus on interventions to improve research participants’ understanding of information disclosed in the informed consent process. There is evidence to suggest that use of multimedia and enhanced consent forms would have only limited success in improving the comprehension of clinical research participants. The most effective approach to improve understanding of patients/participants is extended person-to-person interaction by a study team member or an external educator.[9] Creating awareness about clinical research in society and educating clinical trial participants is critical in improving the quality of informed consent and fostering informed choice regarding participation in clinical research.