Be Informed About Informed Consent
Contrary to popular belief, informed consent defines a process, not a form. The purpose of the informed consent process is to protect the health and well-being of research subjects by providing them access to the information that will allow them to make an informed choice regarding participation in a clinical trial. The process also serves to inform participants about their rights as research subjects. This chapter will explain the process of informed consent.
The History of Informed Consent
The protection of subjects was not always at the forefront of medical research endeavors. It has only been since the last half of the past century that the United States and international medical communities have formally taken steps to protect people who participate in clinical studies. The Nuremberg Code first provided guidance on research ethics and made voluntary consent a requirement of clinical research. Consent was defined as voluntary if participants were able to consent, were free from coercion, and understood the risks and benefits involved. The Code also stipulated that studies should minimize risks and ensure that potential risks not outweigh potential benefits. The Declaration of Helsinki that built on the foundation of the Nuremberg Code defined 12 principles on ethical considerations related to biomedical research, and distinguished between medical care that directly benefits the patient and research that may or may not provide direct benefit. The basis for the creation of institutional review boards (IRBs) and research ethics committees (RECs) can be found in the Declaration.
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) first issued the Good Clinical Practice guidelines in 1996. These guidelines describe the responsibilities and expectations of all participants involved in the conduct of clinical trials and outlines proper informed consent requirements.
The Informed Consent Form
The informed consent form is the foundation of the informed consent process, is a legal document, and is the most important component of study enrollment. However, meeting the intent of informed consent has become difficult in these litigious times because the forms have become cumbersome and difficult for the nonscientific community to interpret. The United States Food and Drug Administration (FDA) mandates certain components that should be included on the informed consent document, including the purpose of the study, the potential risks and benefits, and that participation in the study is voluntary (Table 1). However, the FDA allows a short form to be used instead of the complete informed consent document. The short form simply states that all of the elements of informed consent have been presented orally; a witness to the oral explanation is required. Other countries require similar information.
The United States federal government has suggested several additional elements that may be appropriate to include on the form, or in the oral explanation, depending on the nature of the study and the participants, including termination or withdrawal procedures, any costs, and the number of expected subjects (Table 2). In addition, individual states or institutions may have other requirements for informed consent. Your IRB/REC should be able to assist you with any questions you may have about the requirements of the informed consent form at your facility. Also, even if an informed consent form was supplied by the sponsor, your IRB/REC will have to approve it.
Considerations in Crafting the Informed Consent Document
Having a well-written informed consent form means more than including everything about the trial on a piece of paper. The form must be easy to read and understand and should be written in a language and at a reading level that the majority of potential subjects can understand. Therefore, if the majority of the potential subjects speak a language other than English, the form should be in the language of the participants. However, if only a few subjects will be non-English speakers, you can use the short form with an in-depth explanation of the study in the language spoken by the subject.
Whatever the language of the informed consent form, it should be written so that it is easily understandable by the average person; an eighth-grade reading level or lower is recommended. Technical information should be adequately explained. However, if the form is too long, the potential subjects may not absorb all of the information. Because you will be discussing the content of the form with the subject, it may be more appropriate to provide highlights of the information on the form to complement your conversation. Supplemental information can also be contained in an appendix.
Because a consent form cannot contain all of the information about the disease or the drug, you must direct subjects to additional sources of information. These resources may include Web sites about the disease or the investigational compound, or easily accessible books and periodicals. You may also want to have important journal articles and other information related to clinical trials in general (ie, the process of randomization), and the study in particular, available in your office for those who may want to learn more.
The most important element of obtaining informed consent is knowing that the patient understood the information presented to him or her. Below are some questions that may be included at the end of the informed consent form. These questions should not replace a direct conversation with the potential subject but serve as a record that the subject was provided with the proper information.
The Process of Informed Consent
Deciding to participate in a clinical study is a decision that is often taken very seriously by the potential participants. It is essential that the potential participants have adequate information and the time to make their decisions. Informed consent should first be obtained before you perform any procedures, assessments, measurements, or anything else related to the study on the subject. You should never rush the informed consent process. It is unacceptable for you to hand the informed consent form to the potential subject and demand that he or she make a decision right away. Potential subjects may wish to discuss the study with family, close friends, or religious advisors, or they may want to research the topic of study. Deciding to participate in a clinical study may be particularly difficult if the disease is complex, serious, or life-threatening. You should give the person enough time to digest the information and have any questions answered. He or she should never feel coerced or that there are no other options for care.
Informed consent does not end when the patient agrees to participate and signs the form. Ongoing interaction is essential. If any new information becomes available, such as when a new adverse event is identified, you must inform the participant of the implications of this new information. Also, if any additional tests or procedures are deemed necessary in the course of conducting the study, complete information about the new tests or procedures needs to be provided to the subject, and a new informed consent form may need to be signed.
Consequences of Not Obtaining Informed Consent
Informed consent is the legal embodiment of the concept that individuals have the right to make their own decisions regarding their health and well-being. Legal action can be taken against sponsors, principal investigators, and others involved in the study by subjects who did not freely give informed consent. The basis for these litigations could be negligence, as, for example, in the case of failing to warn subjects about potential risks, or possibly battery for conducting procedures on patients that they did not fully understand. Other laws may also apply and will be discussed in detail in a later chapter. Regardless of the legal ramifications, failure to obtain informed consent should be a moral imperative for everyone involved in the study, and failure to obtain proper informed consent should weigh heavy on the consciences of those involved.
A Note About Prescreening Consent
A prescreening consent form allows investigators to give potential subjects a limited examination and to gather information to see if the person would qualify for a particular study. Significant time for both the potential subject and staff can be saved by using a prescreening consent form instead of undergoing the full consent process. For example, the protocol requires subjects to have a performance status (PS) of 0; a potential subject arrives in the waiting room and signs the short, prescreening consent form; you ask a few simple questions and conduct a brief physical examination, where it is determined that the patient has contact dermatitis (not a PS of 0) and is sent home. Without prescreening consent, valuable time (and money) would have been wasted on obtaining full consent for a person who, on first appearance, met the entry criteria but who was actually ineligible to participate in the study. Like the full consent form, the prescreening consent form and process will need to be approved by your IRB/REC.
Summary
The process of informed consent is one of the most important elements of human research. It has been created for the protection of subjects and the integrity of the research. Having the subject sign the informed consent form is not enough. Subjects must comprehend the potential risks and benefits of participation and what is expected of them during the conduct of the study. Ongoing communication with the subject is essential, especially if any new information about the investigational compound or procedures arise. Remember that research subjects are volunteers, and their best interests should always be kept at the forefront of any research efforts.
Resources
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Good Clinical Practice: Consolidated Guideline. Available at: www.ich.org. Accessed May 15, 2007.
National Cancer Institute. A Guide to Understanding Informed Consent. Available at: www.cancer.gov. Accessed May 15, 2007.
National Institutes of Health. ClinicalTrials.gov. Available at: www.clinicaltrials.gov. Accessed on November 27, 2007.
United States Food and Drug Administration. Code of Federal Register 21 CFR 50.25. Available at: www.accessdata.fda.gov. Accessed May 15, 2007.