In a clinical trial, the Informed Consent Form (ICF) is the main source of information for those considering participating and serves as a legal document to ensure that, as a participant, you have enough information about the study to fully understand what it entails and agree to participate in it.
Many of us have had some medical procedure that required giving written consent, and it generally seems like a simple exercise: be handed a document with information, have the doctor explain the procedure and risks, and if you consent to the procedure, sign the document. In the case of clinical trials, the process of giving informed consent is similar, but more extensive and heavily regulated.
While a signed form from the patient or participant sounds like a straightforward process, it is not always the case. Can minors give consent by themselves? What happens if the person giving consent cannot read? What if they have dementia or are in a coma? Can these people even participate in clinical trials? Let us explain.
Informed consent in research: a fundamental patient right
In clinical research, Informed Consent involves a lot more than just acquiring a participant’s signature on a document. It requires a dialogue between the researcher and the participant to ensure that they are aware and comprehend the nature of the study, its objectives, potential risks, and benefits. Before agreeing to joining any study, as a potential participant, you must be given the chance to ask questions and have them answered, as well as having the time to really wrap your head around all the information.
Moreover, regulatory authorities such as The Food and Drug Administration (FDA), and ethical committees like Institutional Review Boards (IRBs) play a critical role in overseeing the informed consent process. These institutions establish rigorous standards and before approving any clinical trial, they review the documents that will be later shared with participants, to ensure the process is conducted ethically and their rights are protected.
With that said, everyone is different, and the process of giving informed consent will sometimes have to be adapted to a person’s needs. Guidelines for these adjustments and changes to the “standard procedure” are provided by the regulatory authority. As with the standard ICF, these alternative procedures need to be reviewed and approved by both the ethics committee and the regulatory authority before they can be used in a study.
Adaptations of Informed Consent in research
There are many different circumstances in which an adult may not be capable of giving consent.
To be considered informed consent, the person consenting must be able to understand the relevant information presented to them, weigh the risks and benefits of participating in a study, appreciate available alternatives, and communicate their decision. When this is not the case, the person is considered to have an impaired consent capacity.
Third-Party consent
There are many disorders and conditions that can affect a person’s capacity to consent: intellectual and developmental disabilities, stroke, traumatic brain injuries, serious mental illness, intoxication, dementia, Alzheimer’s disease, and delirium.
In situations where a person’s capacity is impaired to the point that they cannot give consent, their Legally Authorized Representative or LAR can do so on their behalf. This is known as third-party consent or consent by proxy. The role of the LAR is to give ongoing support and assume decision-making responsibilities and act in the represented person’s best interest.
A lot of thought and planning goes into deciding whether to allow someone with impaired consent capacity to join a clinical trial. There are steps that are taken to ensure that the participant’s rights are protected, and that the consent process is ethically acceptable. For example, the consent process can include an assessment of the participant’s capacity by an independent, qualified professional, before allowing a proxy to consent on their behalf.
With Alzheimer’s or dementia patients, because it is a progressive disease, it is possible for them to sign up to a research study before their capacity is impaired. However, it is likely that their capacity will become impaired over time. In these cases, the participant can start involving their LAR early in the decision-making process, so that once they are unable to consent for themselves, the LAR can step in.
The role of oral agreements and witnesses in the consent process
There may be situations where a person is unable to provide written consent because they cannot read the form, due to some physical or sensory disability, and the process of giving consent must be adapted to their specific needs.
It is easy to think that the easiest option would be to have a Legally Authorized Representative to sign a third-party consent. While this is a viable option, it is important to bear in mind that people who fall under this category are mentally able to give consent, but not physically able to do so in writing. Therefore, it is not always necessary to involve a LAR, and alternative solutions can be found.
For example, an illiterate person cannot be expected to read and fully understand the consent form. In this scenario, the information on the form can be presented to them orally, and if they agree, they can “make their mark” on the form (equivalent to a signature). It may be necessary to have an impartial witness present during the process, who can certify that the person consents, and can also sign the form. The same can be done for people who are blind or visually impaired.
Informed Consent and minors
Children and minors are considered a vulnerable group in research, due to their lack of autonomy and understanding of what participating in a clinical trial entail, which means that additional safeguards need to be implemented.
In cases where the participant is a minor, it is the parents or guardians that need to give consent for them. Whether one or both parents need to consent is decided by the regulatory agency based on the potential risk of the study. However, even in studies requiring both parents’ consent, there are some exceptions that allow for only one parent to give consent.
Does the child have a say in the decision? In some cases, the minor’s assent is needed as well as the parent’s consent. “Assent” entails a child’s affirmative agreement to take part in the clinical investigation, not just the absence of objection. This is usually done using an ICF that has been adapted so it is easily understood by the minor. Whether or not the minor’s assent is necessary is decided by the regulatory authority, which considers the ages, maturity, and psychological state of the minors that will be involved in the study.
What about minors that become of age while in a clinical study? This situation is more common than you might think. If the child was underage at the time of enrollment, parental consent would have been needed. If a child reaches the legal age while the trial is still ongoing, to continue to participate, he or she would have to consent again by signing an ICF.
Consent form for pregnant participants
Pregnancy is a very specific and complex period in a woman’s life, and while it is not a disease, it can cause symptoms and complications that may require treatment either for the mother, or for the baby.
When a pregnant woman decides to join a study, evidently it could have an impact on the baby as well. Because of this, the process of Informed Consent is far more intricate and heavily regulated. The rules vary depending on the risks involved and potential benefits to both the mother and the baby.
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Clinical trials testing treatment options for a condition specific to the mother
Future mothers are not exempt from medical conditions and might want to join a research trial testing a new medication to treat it while pregnant. In these scenarios, it is likely that the trial’s benefits will only apply to the mother.
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Clinical trials addressing pregnancy-related complications
But there are other situations, in which joining a clinical study can be helpful for both mother and baby. For example, trials that aim to treat pregnancy complications. For these, only the mother’s consent is necessary. However, if the trial is designed to benefit only the baby, both parents would have to sign the Informed Consent Form.
What happens if a woman gets pregnant while participating in research study?
Although, many research studies do not allow pregnant women to participate, and even encourage safety measures to avoid pregnancies during the trial, sometimes women participating do get pregnant. When this happens, the woman will usually stop taking the medication being tested, and the researchers will have to verify if the fetus has been exposed to the study drug or placebo, and for how long.
If it is confirmed that the baby has been exposed to the study drug, the newly pregnant woman will be asked if she consents to having the research team follow up on her pregnancy and baby until birth, or even up to a year after birth.
In some cases, women can be given the option to continue in the study but will have to sign a new consent form that includes the risk to the baby, and any additional risks that may occur due to the pregnancy. They will also be asked if they consent to follow-ups. Collecting this information is important to improve our understanding of the effect of the drug on the pregnancy and the baby.
Ultimately, informed consent is the cornerstone of ethical clinical research, as it ensures that participants understand the study in which they are participating. It protects patient autonomy and the research’s integrity by detailing the study’s risks and benefits. Modifying this process to specific needs of participant is vital, and although the regulatory requirements may seem extensive, they are critical to safeguarding both participants and investigators in clinical studies.