The Role of the IRB and Ethics Committee

Part of Good Clinical Practice (GCP) — ICH E6(R3): Roles and Responsibilities in Clinical Trials.

About 6 minutes. Free, in your language, no account needed.

Why this matters

Independent review is one of the 11 principle categories of ICH E6(R3). No participant may be enrolled before the review body issues its documented approval or favorable opinion. Sites that treat the ethics submission as paperwork tend to discover the problem after enrollment has started, when the only remedy is a reportable deviation.

What the review body is

E6(R3) uses the combined term IRB/IEC. An Institutional Review Board (IRB) or Independent Ethics Committee (IEC) is defined in the Glossary as an independent body, which may be a review board or a committee, and may be institutional, regional, national or supranational. It is made up of medical professionals and non-medical members. Its responsibility is to protect the rights, safety and well-being of human participants.

E6(R3) section 1.2.1 states the purpose in one sentence: "The purpose of an IRB/IEC is to safeguard the rights, safety and well-being of all trial participants." It adds that appropriate consideration should be given to trials that intend to recruit vulnerable participants.

Composition and independence

E6(R3) recommends that the IRB/IEC include:

• at least five members;
• at least one member whose primary area of interest is not in medical sciences;
• at least one member who is independent of the institution or investigator site.

Only members independent of the investigator and the sponsor should vote or give an opinion. Only members who took part in the review and discussion should vote. A list of members and their qualifications is maintained. The investigator, site staff and sponsor may provide information on any aspect of the trial, but they must not take part in the decision making or the vote. The IRB/IEC may invite non-members with specialist expertise to assist.

What the IRB/IEC reviews

Section 1.2.2 lists the material the IRB/IEC should review, where applicable:

• the protocol and amendments;
• informed consent and assent materials and updates, including a description of how consent and assent will be obtained;
• the Investigator's Brochure, or current scientific information such as a basic product information brochure, including updates;
• other trial-related information to be given to participants, including the media used to provide it;
• advertisements for recruitment, if used, and information on the recruitment process;
• plans to compensate participants, if any;
• ongoing updates to safety information;
• the investigator's current curriculum vitae or other evidence of qualifications;
• any other document the IRB/IEC needs.

The IRB/IEC reviews within a reasonable time and documents its review. It identifies the trial, the documents reviewed, and the dates of its approval or favorable opinion, any modifications required before approval, any disapproval or negative opinion, and any termination or suspension of a prior approval.

Continuing review

Review does not stop at approval. E6(R3) section 1.2.4 states that "The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to participants."

Read that carefully. E6(R3) does not fix an annual interval. The interval follows the risk. A first-in-human trial and a low-risk trial in a marketed product do not require the same frequency. Your local law or the review body's own procedures may state a fixed maximum interval, and that requirement still applies.

The IRB/IEC procedures must also specify:

• that no participant is enrolled before the IRB/IEC issues its documented approval or favorable opinion;
• that no deviation from or change to the protocol is initiated without prior documented approval of an appropriate amendment, except where necessary to eliminate immediate hazards to participants, or where the change involves only logistical or administrative aspects and local requirements allow;
• that the investigator or institution promptly reports deviations made to eliminate immediate hazards, changes that increase risk or significantly affect trial conduct, all suspected unexpected serious adverse reactions (SUSARs) in accordance with applicable regulatory requirements, and new information that may adversely affect participant safety or trial conduct.

The IRB/IEC in turn promptly notifies the investigator, institution or sponsor in writing of its decisions, the reasons for them, and the procedure for appeal.

Participant payment and coercion

Section 1.2.8 is short and frequently examined. If participants are compensated, the IRB/IEC reviews both the amount and the method of payment, to assure that neither creates coercion or undue influence. E6(R3) then states:

"Payments to a participant should be timely, prorated and not wholly contingent on completion of the trial by the participant. Reasonable reimbursement of expenses incurred by participants, such as for travel and lodging, is not coercive."

Two conclusions follow. Reimbursing a participant's bus fare is not a payment problem. Holding all payment until the final visit is a payment problem, because it pressures a participant to stay in a trial they may want to leave. Payment information, including methods, amounts and schedule, must appear in the informed consent materials.

In practice

Description. Recruitment at Dr. Sarah's hypertension site is slow. The site manager proposes a single payment of the local equivalent of one month's average wage, paid only to participants who complete all twelve visits. The proposal is added to the recruitment leaflet and the leaflet is printed.

Ethical dilemma. The amount is large relative to local income, and the payment is wholly contingent on completion. Both features press a participant to continue when they might otherwise withdraw. That undermines the voluntariness of participation. The leaflet is also participant-facing recruitment material that the IRB/IEC has not reviewed.

Resolution. Ana stops the leaflet before it is used. Nothing participant-facing is distributed before IRB/IEC review. Dr. Sarah and the sponsor revise the plan so that payment is prorated across visits and paid in a timely way, with travel and meal costs reimbursed separately against receipts. The revised payment schedule is written into the informed consent materials. Both the leaflet and the revised consent materials go to the IRB/IEC, and recruitment waits for the documented opinion.

Independent review protects the participant first and the trial second.

Key takeaways

• The purpose of the IRB/IEC is to safeguard the rights, safety and well-being of all trial participants, with particular attention to trials recruiting vulnerable participants.
• No participant may be enrolled before the IRB/IEC issues its documented approval or favorable opinion.
• Continuing review happens at intervals appropriate to the degree of risk to participants, not at a single interval fixed by ICH E6(R3).
• E6(R3) recommends at least five members, including at least one whose primary interest is not in medical sciences and at least one independent of the institution or site.
• Participant payments should be timely, prorated and not wholly contingent on trial completion, and reasonable reimbursement of expenses such as travel and lodging is not coercive.
• A protocol may only be changed without prior IRB/IEC approval to eliminate an immediate hazard to participants, and the change must then be reported promptly.