Putting the “Informed” in Informed Consent
“Informed consent is not a signed piece of paper bur, rather, the fluid, continuous process by which a researcher informs the subject in detail of what he or she proposes to do, why it is being proposed, and what possible consequences the experiment carries.” -Harriet Washington, Medical Aparthaid
History of Informed Consent
Up until the end of World War II, physicians and scientists were able to conduct research on patients without their permission, and sometimes even without their knowledge. Horrific medical experiments performed by researchers under the Nazi regime during World War II were captured and tried for their crimes during the Nuremberg Trials. The judges and doctors representing the prosecution produced the Nuremberg Code, a set of research ethics principles for human experimentation, which was adopted by the United Nations in 1948. The first of its kind, this document laid out the essential components of research involving human subjects, with its first point being “voluntary consent.”
While the Nuremberg Code was a step in the right direction, it was never put into law or made a regulation by governing bodies, and unfortunately, this allowed some of the most infamous cases of research, without the consent of patients, to make their way into the history of clinical research. Researchers continued to escape punishment for their unethical research practices during this time by using marginalized groups such as African Americans, orphans, developmentally disabled individuals, mentally ill patients, and those in a class having the lowest social rank or standing due to low income, lack of skills or education. The people in these groups were often unable to decide whether they wanted to participate in certain “research trials”, and researchers justified their unethical behavior citing the work would be for the greater good of society. Additionally, people of a higher status and/or position of power generally did not care about these groups of people. Since the Nuremberg Code did not have legal authority, these individuals had no protections in place that are commonplace today.
Image: Researcher and participants in the Tuskegee Syphilis Study, Wikipedia
A Worst Case Scenario
One of the most famous cases of clinical research, the Tuskegee syphilis study, actually began before the Nuremberg Code was published, and continued into 1972. This study recruited hundreds of African American men with syphilis, though they were not aware that what they had was syphilis. Indeed, they were told they had “bad blood.” The goal of the study was to study the progression of the disease without treatment, which was not very effective until the mid-1940s when penicillin became available. However, even when penicillin was promoted as the best-known treatment for syphilis, the researchers opted to continue to passively observe these men rather than treating them, which resulted in many men dying, going blind, or developing other health problems as their disease progressed.
Had informed consent been a common and required practice for clinical research, these men would have been informed of their syphilis infection, saving their wives from contracting it and their children from being born with congenital syphilis. The researchers would also have been required to inform them that they now had a treatment, penicillin, sparing them from the agony of the disease progression. The study was finally shut down in 1972 after a journalist published an article about the study, prompting an advisory panel to look into it and deemed it “ethically unjustified.”
Image: Flowchart of the informed consent process, PMID: 23533976
Since then, the Belmont Report and the International Conference on Harmonization (ICH) have developed guidelines for human subjects research, and federal regulations have been established through the Food and Drug Administration (FDA) and the Department of Health and Human Services (HHS). Researchers now face legal complications and potential loss of
their license to practice medicine and/or perform clinical research if they do not comply with these regulations. These regulations implemented practices such as Institutional Review Boards to oversee study protocols, financial disclosures for those involved in research, and informed consent.
What Does Informed Consent Look Like?
Even if someone has never been in a clinical research study, they have likely encountered the informed consent process during the course of regular medical care, as informed consent is required before undergoing procedures, even minimal risk procedures such as wisdom teeth removal. The consent will outline the procedure, its risks and benefits, and potential side effects. With the exception of emergencies, it is generally required that a patient sign a consent form before undergoing a procedure in the United States.
While consent forms may be rather standardized for well-established medical procedures, consent forms can differ in many ways in the scope of clinical research due to the novel nature of research. For this reason, consent documents go through rigorous scrutiny before making their way into the hands of patients. The consent document itself must contain several points to truly be “informed.” These include describing the nature of the research, potential benefits and risks, alternative treatments, and letting the participant know how the research team will be involved with the patient’s care during the time of the project. Patients are to be given ample time to review a consent document and ask questions or raise concerns to the research team before signing the consent form and enrolling in a research project. For clarity no research procedures, even those as simple as getting a patient’s height and weight, should be performed before the consent is signed.
Though informed consent is standard practice, it can look different depending on a number of factors. For example, someone who is unable to read or write will still be allowed to consent to a study but must have an impartial witness (someone not affiliated with the study or related to the patient) present to read the consent to them. Additionally, researchers and research sponsors have made strides to include demographics in their study that are representative of the overall population. They must include individuals from different racial and ethnic backgrounds, many of whom come from different cultural backgrounds and practices. Most institutions now have medical interpreters trained to assist patients in their medical care and research, but it is also vital to have staff familiar with the cultural factors that may come into play when consenting patients from a different background. This will help ensure that patients are not feeling coerced and that they understand the research being presented to them.
One of the most common considerations in informed consent is whether or not a patient has the capacity to consent, which is an individual’s ability to understand and decide about participation. Capacity to consent can vary due to mental disorders (i.e. schizophrenia, dementia, developmental delays), neurological conditions (Alzheimer’s disease, stroke, head trauma), substance abuse, and even use of certain medications. In instances where researchers believe an individual does not have the capacity to consent, they will go through the informed consent with the patient’s legally authorized representative (LAR), who is someone related to or has a close relationship with the patient and can make decisions that are in the patient’s best interest and that are believed to be what the patient would want. LARs are critical in research, as they allow researchers to include patients who may not have the capacity to consent, so that progress can be made on understanding and/or treating their condition.
Lastly, there exist situational factors that may influence someone’s willingness to participate in a research study. Many clinical trials include compensation that can vary from hundreds to thousands of dollars, and researchers must pay attention to a potential subject’s motive to participate to ensure that people are not just participating for the compensation. Scrutiny must also be given in terms of a patient’s situation and state of mind. For instance, someone who has just been diagnosed with an incurable disease may not be in the best state of mind to think through a consent form and commit to a clinical trial. Researchers must take account of all of these considerations and countless others.
The past injustices resulting from a lack of informed consent from patients have shed light on the value and importance of informed consent . Modern clinical studies still have the same goal of advancing medical science for the benefit of human beings, but clinical researchers and patients are equal stakeholders in these studies. A thorough informed consent process is beneficial not just for patients, but for researchers as well. Patients who understand the research they’re participating in are also less likely to withdraw from the study, as some of the reasons participants withdraw include schedule conflicts, side effects, and a misunderstanding of expectations, which are topics that should be discussed during the informed consent process of a study. When patients understand the study and adhere to what they’re asked to do, the resulting data will likely be useful, clearer and more comprehensive. This in turn, will provide better care for patients and better science for researchers to continue to study disease and develop treatments.
Written by Amanda Wilburn, BA