Informed consent is a process, not just a form signed by prospective study subjects. Documents such as the Code of Federal Regulations describe the elements of informed consent, but lack substantive direction on the process of obtaining consent.1-2 The purpose of this article is to provide guidelines for obtaining informed consent. This guide can be useful to anyone involved in clinical research, particularly newcomers to the industry.
The process of obtaining informed consent from subjects is a critical point of entry for research participants. Although the basic principles of obtaining informed consent transcend therapeutic areas and vulnerable patient populations, significant differences must be considered when research designs include individuals at increased risk. Special attention must be given to meeting the needs of vulnerable populations such as children, the critically ill, or the mentally impaired. The atmosphere for the family of a trauma patient during the first few critical hours of admission is far removed from the unhurried pace of the outpatient clinic. The focus of this article, however, is the process of obtaining consent from a population of patients who are not under duress at the time of consent.
Typically, the introduction of a potential subject to a clinical trial occurs in one of the following ways:
Although there are several ways that patients learn about clinical trial "little is known about the factors that influence decisions to participate in scientific research."3 Kuczewski and Marshall recommend adopting the approach that consent is an interactive and dynamic process and many factors can influence the study participant's willingness to sign the document. These factors include socioeconomic background, cultural traditions, literacy and language ability, and interactions with physicians and other healthcare professionals.
Bosk found "what, how, and when information is presented does make a difference to a subject's understanding of research and to subsequent enrollment."4 The investigator should carefully weigh the consequences of trying to obtain consent after the patient has just been diagnosed with a life-threatening illness. A subject's ability to make decisions may also be affected by his/her emotional state.5 Emotional stress can be a cause of failure to consent. It is recommended that the subject be given a week to accept her diagnosis before discussing enrollment in the study.
Trechan found that risk levels influence a subject's willingness to participate in clinical research.6 Furthermore, negative media attention, such as Ellen Roche's death at Johns Hopkins, may adversely affect decisions to participate.7 Getz suggests that subjects who successfully complete other clinical trials are more likely to consent again.8
Problems with the consent process The informed consent process presents some major challenges for study participants and research staff. Several papers have addressed problems with the current process. Among them, Brady identifies the following issues:9
Additionally, a survey of 1600 respondents performed by CenterWatch in 2002 found that 14% of subjects did not read the consent before signing, and a high percentage of volunteers admitted to not fully understanding the risks and not knowing what questions to ask. The concept of "therapeutic misconception" in research is another problem that has received much attention in both legal and bioethics literature. Generally, it is important that potential subjects are aware that research is not the only therapeutic alternative for them.10-12 Lack of subject understanding and comprehension is possibly compounded by the increasing regulations that govern the performance of study personnel and the cost pressures, meaning that there is ever-decreasing time available for study personnel to spend reviewing the consent with the subject.
Setting The informed consent process begins when a potential subject is first approached to participate in a clinical trial. Whether informed consent is obtained over the phone (remember-there may be a specific protocol for doing this at your institution), or in a doctor's office or hospital, the setting should be the same. It should be an unhurried, private atmosphere where the subject has time to review the document and ask questions. The subject should be approached in a respectful manner and the person obtaining consent should introduce themselves by name and role, stating the purpose of their communication. As already indicated, the timing of this process is very important.
The person obtaining consent must have appropriate credentials and be qualified to do so. She/he should have experience in the field of study-otherwise, how will she answer questions posed by the subject? Additionally, this person should be familiar with good clinical practice guidelines for informed consent and with his/her own institutional review board's requirements for the process.
The researcher should determine the ability of the potential subject to understand the information and give consent before proceeding further. If the subject does not read or speak English adequately, an assessment should be performed to determine the subject's needs. The researcher should then make the decision to call in an interpreter. Kuczewski and Marshall suggest that misunderstandings are more likely to occur when investigators (or coordinators) and participants speak different languages, especially when "there are no equivalent expressions for particular biomedical concepts or when the notion of informed consent is unfamiliar." They offer strategies to help minimize language barriers:
Use an effective process of translation and back-translation when an informed consent document must be translated from one language to another. This process must include adequate pretesting of the consent document to determine that it is comprehensible to individuals who will be recruited for a research project.
Enlist the help of individuals who can act as "cultural experts" on ways in which to communicate difficult scientific concepts for study populations who may be unfamiliar with the biomedical problem being investigated.
Keep the consent document as short as possible, using simple language and a format that is clear and understandable for potential research participants.
The issue of using family members when there is a language barrier is a gray area. Most subjects feel more comfortable if one or more family members are available to help them with decision-making, though this is not always the case. Additionally, excluding family or friends from the discussion may eliminate bias for or against participation; however, this must be balanced with the subject's wishes. Tailor the discussion to the subject's needs.