Informed Consent in Clinical Trials: What Is It and How It’s Obtained

Clinical trials are a critical part of the wider medical research landscape, and there are many reasons why someone might decide to participate in one. Some people get involved to advance scientific research, while others may see it as their best or only option for the treatment of a condition.

Regardless of why someone participates in a clinical trial, their involvement is always voluntary and they can choose to opt out at any time. Since clinical trial participation is voluntary, every participant needs to go through what is known as an informed consent process on a consistent basis.

What is informed consent in clinical trials?

Informed consent in a clinical trial is the process of participants confirming their willingness to participate in a particular study. During the informed consent process, participants will be informed of all aspects of the study, ensuring they fully understand it before agreeing to take part or continue with it.

As new drugs, treatments, and devices are developed, no one knows for sure how well they will work or what risks will be found. This is why it’s important for people participating in a clinical trial to understand their role as a ‘subject of research’ and not a patient of a known medical treatment.

The Informed Consent Form (ICF) is the main source of information for people thinking about getting involved in clinical research. This form is used by researchers to document a participant’s informed consent both at the beginning of the trial and throughout.

What are the four pillars of informed consent?

Many researchers in the clinical trial landscape abide by what is known as the ‘four pillars of informed consent’. This ensures the informed consent process is carried out as per best practice so it can be completely effective for both participants and research teams. It includes:

• Information: Research professionals should provide relevant details of the study, including its purpose, procedures, risks, benefits, and alternative treatments that may be available. Participants can use this information to inform their decision on whether to participate.
• Voluntariness: Researchers must ensure participation in a trial is always entirely voluntary, without methods of coercion or undue influence used at any stage of the study.
• Comprehension: As part of the process, researchers should ensure all participants understand the information that is provided to them. They should also give participants the opportunity to ask questions about the trial and clarify any queries they have before agreeing to participate.
• Competence: Researchers must assess and confirm all participants understand the information provided to them so they can ensure their willingness to participate is fully informed and voluntary.

Why is informed consent important in clinical trials?

Once informed consent is obtained, researchers can be sure that the participant knows every aspect and detail of their participation in the trial. This includes what procedures or treatments will be given, how they will be performed, and any potential outcomes, including the benefits and risks of the trial.

There are several key reasons why informed consent is so important:

• Informed consent protects patient autonomy and human rights by ensuring participants are free to make their own decisions.
• It ensures patients are fully informed with all the information they need to make informed decisions about their care, including details about potential risks, benefits, alternatives, and consequences.
• It is a fundamental part of good medical practice that ensures patients are listened to and that they can make the right decisions for their personal circumstances.
• Informed consent protects health professionals by providing them with a defense against claims or assault, while also supporting them in making ethical decisions.
• It ensures participants in research or medical treatment give their consent voluntarily, without coercion or pressure.
• Obtaining informed consent aligns with ethical principles by promoting transparency, honesty, and respect for the decisions made by participants, ensuring the welfare of participants is prioritized over societal interests.
• Informed consent gives individuals the opportunity to be involved in their own healthcare decisions. By having all the information about the trial, participants can make informed choices that align with their values and preferences.
• Informed consent allows participants to consider the potential risks and benefits of taking part, letting them assess whether the research aligns with their circumstances and expectations.
• The FDA, and other regulatory bodies, require researchers to obtain informed consent to ensure compliance with ethical and legal standards. Non-compliance can lead to serious consequences, including invalidation of the study results or legal ramifications.

When is informed consent obtained?

Informed consent should be obtained before any research procedures start, and is the first step in a clinical trial after suitable candidates have been found. Researchers must also ensure informed consent is obtained consistently throughout the trial, especially if treatments or other circumstances change. The only time informed consent is waived is during emergency situations when it might be unfeasible to gain informed consent from the participant, for example, if they are critically ill.

How is informed consent documented?

Informed consent is usually documented in two ways, on paper and electronically. Both verbal and written consent from participants must involve the informed consent process, but obtaining written consent is more than just signing a form.

Documentation involves using a written consent form that includes all the information to be disclosed to participants and should be signed by the participant or their legally authorized representative (LAR). Use of a LAR when gathering consent from minors or those who are cognitively or medically impaired requires prior institutional review board (IRB) approval.

Informed consent in a virtual clinical trial

As virtual clinical trials become more commonplace, informed consent must adapt accordingly. In virtual clinical trials, informed consent is usually obtained via electronic consent (e-consent), which involves a discussion between the participant and a research professional via video link or telephone. This is usually followed by written confirmation of consent.

As with regular informed consent, participants are given ample opportunities to read the written information about the trial and ask questions. They can then discuss the trial in more detail with the researcher and ensure they fully understand everything they need to know before agreeing to take part. In most cases, participants can provide informed consent by email, letter, or verbally during a recorded telephone or video call. After this, the researcher will document the consent by recording and retaining evidence of it.

Informed consent in a decentralized clinical trial (DCT)

Decentralized clinical trials (DCTs) use a combination of virtual and face-to-face elements, but informed consent is still a necessity, as it is for all types of trials. Informed consent in DCTs is obtained through a variety of methods, including electronic, video consultation, online identity verification, e-signatures, and smartphone apps.

Informed consent in trials involving minors

Informed consent for minors in pediatric clinical trials involves multiple steps that set it apart from the regular informed consent process. Firstly, the regulatory agency of the trial decides who can give consent based on any potential risks of the study. In the US, minors under 18 cannot give informed consent, which means researchers must obtain assent from the minor and permission from their parents or guardians. This is the minor’s affirmative agreement to take part.

The method for obtaining consent from a minor must also be appropriate for the minor’s communication abilities. For example, a minor might sign, circle an emoji, or add a sticker to their documentation. Likewise, the consent form should be adapted so minors can easily understand it in a way that makes sense to them.

Another factor for consideration is whether minors will reach legal age while participating in the trial, especially as many clinical trials can progress over the years. If this happens, the minor must consent to continue participating in the trial when they reach this age.

Informed consent in trials involving incapacitated adults

In some cases, adults who are incapacitated either physically or mentally may not be able to provide informed consent. In the US, informed consent for incapacitated adults must be obtained from a legally acceptable representative (LAR). The LAR is an individual or legal body authorized to provide consent on behalf of the participant. They should be appropriately qualified and not subject to potential conflicts of interest, and they must also be properly acquainted with the patient and available during the trial.

In these cases, the investigator must make sure the potential participant understands the research and the potential risks or benefits involved. They should ask open-ended questions to help the participant think more carefully about the study and what is required of them, while also giving them the opportunity to raise any questions.

If the participant or LAR is unable to read or write, researchers must ensure an impartial witness is present during the informed consent process so they can sign the form on their behalf. In rare cases, a participant may be allowed to take part in the trial without informed consent. Common reasons for this are if the study has been approved by a research ethics committee, it is necessary to act urgently, or it is not reasonably practicable to obtain informed consent before starting the study.

When is a witness signature required?

For some participants or specific clinical trials, a witness signature may be required. This is often the case for participants who are not able to make decisions by themselves, for example, minors or incapacitated adults. The witness must be an adult and impartial, which means they are not a family member of the participant, a trial participant, or a member of the research team.

The most common circumstances for witness signatures being required include using an IRB-approved foreign language short form process for participants who do not speak the local language, or when obtaining informed consent from a participant who is physically unable to read, write, talk, or is blind.

The informed consent process

There are several steps involved in the informed consent process for clinical trials, and researchers need to ensure they are all carried out to obtain informed consent as per best practice.

• Study explanation: Participants selected as suitable for the trial should be informed that the clinical trial involves research. They must be given a clear description of the trial's purpose, procedures, expected duration, and experimental interventions like medication, devices, or treatments.
• Risks and benefits: Researchers must outline any potential risks, discomforts, or side effects associated with the study before a participant agrees to take part. They should also explain any expected benefits or advancements in medical knowledge that may arise from the research.
• Alternative treatments: Participants must be given information about the alternative treatment options available, if any, and the potential benefits or risks associated with them.
• Confidentiality and privacy: Researchers need to explain how they will protect the confidentiality of participant information and how they will use any collected data. They may also inform participants that regulatory inspections may occur during the study.
• Compensation and medical treatments: If the study involves compensation, researchers should clearly explain all the details. This must include the extent of any compensation, whether participants will be reimbursed for expenses like transportation, and the availability of medical treatments outside the study.
• Contact information: A list of who to contact if a potential participant has more questions or needs to understand more about their rights must be provided by researchers. This should also detail who to contact if a research-related injury were to occur.
• Voluntary participation: Participants should be informed that their participation in the trial is completely voluntary and they have the right to decline or withdraw from the study at any time without penalty or loss of any entitled benefits. This information must also outline whether there are possible consequences of leaving a trial before it is completed. For example, the investigational therapy may require a slow tapering of dosage to avoid withdrawal symptoms.
• Understanding and questions: Researchers should ensure participants completely understand the information provided to them by asking questions and encouraging them to seek further clarification.
• Documentation: Once the participant has understood the study and its implications, they will need to sign a written consent form. This document confirms their voluntary agreement to participate and becomes a record of the informed consent process.
• Ongoing communication: Throughout the study, researchers should maintain open lines of communication with all participants. They should provide updates on the progress of the research, address any emerging issues, and quickly inform participants of any relevant changes to the study protocol or potential risks.

How can informed consent best practices be ensured in clinical trials?

While researchers must ensure they have provided all the information participants need to make an informed decision, they must also ensure the entire informed consent process is carried out to best practices. There are a number of steps they can take to ensure this.

Firstly, researchers must receive adequate training on GCP principles and procedures for obtaining informed consent. This must happen before any participants go through the informed consent process to ensure researchers can communicate effectively with a range of people, understand cultural sensitivities, and address any potential challenges.

Researchers must ensure they avoid technical jargon and complex terminology, instead using language that participants from a range of educational backgrounds and cultures can understand. Research teams should also make sure the informed consent process takes place in a private but comfortable setting, giving participants the opportunity to ask questions and express any concerns they may have about the study.

When filling in the consent form, researchers must write them in clear and concise language that the participants will understand. Their documents should contain all the information about the study including its risks, benefits, confidentiality, compensation, and research team contact details.

Throughout the study, regulatory bodies and ethics committees should conduct regular monitoring and auditing to make sure the study is compliant with the informed consent requirements. This is an important step in maintaining the integrity of the research process while protecting participant well-being and human rights.

When is informed consent not necessary?

Informed consent is mandatory in all clinical trials for all participants after the institutional review board (IRB) or ethics committee has approved the study to go ahead. However, there are a small handful of occasions where informed consent is not required. These include:

• In studies where participants have been deemed incompetent to give consent, researchers may not need to obtain it.
• Research using anonymized tissue samples.
• Studies that involve the use of imported tissues or tissues collected before September 1st, 2006.
• Studies using an intervention that involves the entire target community, and therefore single subjects cannot refuse it.
• Emergency situations when a person is unconscious or otherwise unable to make a decision. In cases where a person needs emergency treatment to save their life, obtaining informed consent may not be possible or required.

Conclusion

Informed consent is a fundamental part of clinical research and those involved in the planning or functioning of a clinical trial must ensure this is obtained from every participant both before and during the study. Without informed consent, studies simply cannot go ahead and the medical research landscape could see fewer medical innovations being discovered.

If you’re keen about getting involved in a clinical trial, informed consent is the first aspect you need to understand before you agree to participate.