What ICH E6(R3) Expects on Independence and Disclosure

Part of Conflict of Interest in Clinical Research: GCP and International Expectations.

About 5 minutes. Free, in your language, no account needed.

Expert review pending. CRLN wrote this lesson against the primary sources listed under References. A subject-matter expert has not yet reviewed it. Where your institution's policy or your sponsor's instructions are stricter, follow them.

Why this matters

ICH E6(R3), the international Good Clinical Practice guideline adopted at Step 4 on 6 January 2025, is the shared baseline for sites in many countries. It does not contain a financial disclosure rule like FDA's, and it sets no dollar thresholds. What it does is build independence into the structure of a trial and require that money and influence be visible and documented. Knowing where those requirements sit lets you connect your local rules to the global standard.

Independent review

ICH E6(R3) says clinical trials should be subject to independent review by an institutional review board or independent ethics committee (IRB/IEC) (Principle 3). The guideline recommends that an IRB/IEC include at least one member who is independent of the institution or investigator site, and it says that only members who are independent of the investigator and the sponsor should vote or provide an opinion (Annex 1 §1.3.1).

For site staff this means two things. You never take part in the IRB/IEC's decision on your own study, and if you also serve on an IRB/IEC, you step out of the vote on any study where you or your site has a stake.

Committees with managed conflicts

Sponsors often set up committees that can affect participant safety or the reliability of results, such as an independent data monitoring committee or an endpoint adjudication committee. ICH E6(R3) says such committees should include members with relevant expertise and with managed conflicts of interest, have written operating procedures and document their decisions (Annex 1 §3.9.9). An investigator invited to sit on one of these committees should expect to be asked about interests, and should disclose.

Money is documented, not hidden

The financial aspects of the trial should be documented in an agreement between the sponsor and the investigator or institution (Annex 1 §3.5). In the guideline's table of essential records, the arrangement between parties on the financial aspects of the trial is listed among the records that should generally be in place before the trial starts (Appendix C).

At a site, this is usually the clinical trial agreement and its budget. It matters for conflicts because it is the record of what the sponsor pays and to whom. Payments that fall outside it, such as a personal consulting arrangement, are exactly the ones that need separate disclosure.

Payments to participants

Conflicts are not only about staff. The IRB/IEC should review both the amount and the method of payment to participants to make sure neither presents problems of coercion or undue influence. Payments should be timely, prorated and not wholly contingent on completion, and reasonable reimbursement of expenses such as travel and lodging is not coercive (Annex 1 §1.2.8). Payment information belongs in the consent materials (§1.2.9), and the consent discussion covers anticipated prorated compensation and anticipated expenses (§2.8.10).

No coercion or undue influence by staff

Neither the investigator nor site staff should coerce or unduly influence a participant to take part or to continue taking part (Annex 1 §2.8.3). A staff member whose pay, bonus or standing depends on enrollment or retention has a reason to push. That is why such incentives are a conflict of interest question, not only a budget question. Module 4 returns to this.

Qualified, informed, overseen

Investigators should be qualified by education, training and experience (Annex 1 §2.1.1). The investigator may delegate trial activities but keeps ultimate responsibility and oversight (§2.3.1) and should make sure delegates are qualified and informed about their tasks (§2.3.2). A conflict that affects a delegated task, such as a rater with a stake in the outcome, is part of what that oversight must catch.

What E6(R3) leaves to local rules

ICH E6(R3) does not define "conflict of interest" for investigators, does not list disclosable interests, and does not set amounts or time windows. Those come from national law, ethics committee requirements, institutional policy and sponsor procedures. The guideline repeatedly points to "applicable regulatory requirements," and that is where the detail lives.

In practice

An investigator in a multinational trial is asked by the sponsor to join the endpoint adjudication committee. The committee charter asks for a declaration of interests. He lists his consulting agreement with the sponsor. The sponsor decides he can sit on the committee but must not adjudicate events from his own site, and records that in the committee's documentation.

Key takeaways

References