Principles of Informed Consent and Participant Autonomy

Part of Good Clinical Practice (GCP) — ICH E6(R3): Informed Consent Process.

About 7 minutes. Free, in your language, no account needed.

Why this matters

Consent problems are among the most common findings at inspected sites. A signature on the wrong form version. A procedure done before the discussion. A participant who cannot say what the trial is for. Each is a failure of respect before it is a failure of paperwork.

Informed consent is a process, not a signature

That sentence is the spine of this module. The signature records a decision. It does not create one.

Principle 2 of the International Council for Harmonisation (ICH) guideline ICH E6(R3) reads:

"Informed consent is an integral feature of the ethical conduct of a trial. Clinical trial participation should be voluntary and based on a consent process that ensures participants (or their legally acceptable representatives, where applicable) are well-informed."

Principle 2 has four sub-points.

• 2.1 — freely given and documented. Consent should be obtained and documented from every participant before participation. Where a person cannot consent, a legally acceptable representative acting in their best interest consents for them. Those participants should still be informed in a way that helps them understand. Where a minor takes part, assent should be collected as appropriate. Principle 2.1 cross-refers to ICH E11(R1) for pediatric trials.
• 2.2 — the point of the process. The process and information should enable potential participants to evaluate the benefits, risks and burden and to make an informed decision, in language clear and concise enough to be understandable.
• 2.3 — context matters. The process should take account of the characteristics of the participants, the trial design, the anticipated benefits and risks, the setting and context (for example, emergency trials) and the potential use of technology to inform participants and obtain consent.
• 2.4 — emergencies. Where consent cannot be obtained before participation, it should be obtained from the participant or representative as soon as possible, following applicable regulatory requirements and the process approved by the institutional review board or independent ethics committee (IRB/IEC).

Think of a tenant taking a lease. The landlord explains the terms, the tenant asks questions and takes time to think, then signs and keeps a copy. The conversation was the agreement.

What E6(R3) section 2.8.1 requires of the process

Section 2.8.1 states that in obtaining and documenting consent, in paper or electronic format, the investigator should comply with applicable regulatory requirements and adhere to GCP and to the ethical principles originating in the Declaration of Helsinki. It lists five components.

• (a) IRB/IEC approval first. Before consenting and enrolling participants, the investigator should have the IRB/IEC's documented approval or favorable opinion of both the consent materials and the process.
• (b) Clear and concise. The information should be as clear and concise as possible, use simple language and avoid unnecessary volume and complexity. The aim is adequate understanding of the objectives, alternatives, benefits, risks, burdens, the participant's rights and what is expected of them.
• (c) Varied approaches. Text, images, videos and other interactive methods may be used. The characteristics of the population should be considered, and E6(R3) gives the example that participants may lack familiarity with computerized systems. Where computerized systems are used to obtain consent, participants may be given the option of a paper-based approach instead.
• (d) Remote consent. Obtaining consent remotely may be considered where appropriate.
• (e) Identity. Whether the process is in person or remote, the investigator should assure themselves of the identity of the participant or representative, in accordance with applicable regulatory requirements.

Sub-points (c), (d) and (e) show that E6(R3) is written for modern, distributed trials. A long paper form is not the only lawful method. A short video with subtitles may produce better understanding than dense text. But technology is never a default, and a participant who has never used a tablet should be offered paper. Remote consent adds one duty: agree with the sponsor and the IRB/IEC in advance how identity is verified and recorded.

Who may conduct the discussion, and how much time

Section 2.8.5 states that the process should be conducted by the investigator, or by delegated investigator site staff, in accordance with applicable regulatory requirements. Consent is a delegated activity. It belongs on the delegation record, and the person performing it must be trained on the current protocol and consent version.

Section 2.8.6 requires the participant or representative to be given ample time, unless justified (for example, in an emergency situation), and an opportunity to inquire about trial details and to decide. Questions should be answered to their satisfaction. "Ample time" is not a fixed number of hours. It depends on the trial, the risk and the person.

Voluntariness, coercion and undue influence

Section 2.8.3 states that neither the investigator nor investigator site staff should coerce or unduly influence a participant to take part, or to continue. Undue influence is gentler than coercion, which is why it is missed. Examples:

• Payment that is too large — money that makes the decision for a person who needs it.
• Promising better care — implying that participants get superior treatment or faster access.
• Using the treating relationship — a doctor urging their own patient to enroll, where the patient fears disappointing them.
• Pressure of timing — telling a person the last slot closes today.

Payment itself is not the problem. Section 1.2.8 requires the IRB/IEC to review the amount and method of payment for coercion or undue influence, and confirms that reasonable reimbursement of expenses such as travel and lodging is not coercive.

In practice

Mr. Smith arrives at his second visit and says he wants to sign today. His doctor, he says, told him this is his best chance.

Nadia, the coordinator, does not hand him the form. She uses the teach-back method and asks three open questions. What is this study trying to find out? What will happen to you if you take part? What happens if you stop?

Mr. Smith answers the first two well. On the third he says he would have to leave the clinic and lose his usual doctor. That tells Nadia the discussion is not finished. She explains that withdrawal carries no penalty and no loss of the care he is otherwise entitled to. She also corrects the idea that the trial is a treatment chosen for him.

He takes the materials home and signs two days later. Nadia records the discussion, his questions and the version used. Enthusiasm is not understanding. Test understanding, not agreement.

Key takeaways

• Principle 2 requires participation to be voluntary and based on a process that leaves participants well-informed, in language clear and concise enough to be understandable.
• Section 2.8.1(a) requires documented IRB/IEC approval of both the consent materials and the consent process before any participant is consented or enrolled.
• Section 2.8.1(c) permits varied approaches such as text, images and videos, and allows a paper-based alternative when computerized systems are used.
• Section 2.8.1(d) allows remote consent where appropriate, and 2.8.1(e) requires the investigator to assure themselves of the participant's identity either way.
• Section 2.8.5 restricts the discussion to the investigator or delegated site staff, and 2.8.6 requires ample time and an opportunity to ask questions unless an emergency justifies otherwise.
• Section 2.8.3 prohibits coercion and undue influence, while 1.2.8 confirms that reasonable reimbursement of travel and lodging expenses is not coercive.