Informed Consent for Investigator-Initiated Trials: A Practical Design Guide

Informed consent is not a signature event. It is the process through which a prospective participant receives relevant information, has a real opportunity to ask questions, decides voluntarily, and can reconsider participation as the study continues.

That distinction matters in an investigator-initiated trial (IIT). When the investigator or institution also controls sponsor-level activities, the team cannot assume that an external company has aligned the protocol, participant materials, operational workflow, and document controls. Exact legal responsibilities depend on jurisdiction, intervention, institution, and study type, but the investigator-sponsor must assign them before enrollment.

Start with What is an Investigator-Initiated Trial? and connect this workflow to the approved IIT protocol.

Start with governing requirements—not a generic template

There is no universal checklist sufficient for every IIT. Identify the jurisdiction, intervention type, ethics board, institutional privacy and accessibility requirements, whether electronic or remote processes are permitted, and requirements for populations needing additional protections.

ICH E6(R3) describes informed consent as integral to ethical trial conduct and emphasizes voluntary participation based on adequate information. In Canada, TCPS 2 describes consent as free, informed, and ongoing. FDA-regulated clinical investigations must address applicable elements in 21 CFR 50.25, supplemented by FDA guidance. These sources overlap but are not interchangeable. A local template does not replace jurisdictional assessment.

Download the editable IIT informed consent template

Use this Microsoft Word template as a structured authoring framework—not as a universal or pre-approved consent form. It includes a participant-centered Key Information section, core and optional clauses, document controls, IIT-specific sponsor and oversight prompts, signature options, and author instructions grounded in current NIH, FDA, HHS/OHRP, and ICH E6(R3) frameworks.

Before use: replace every bracketed prompt, remove drafting instructions and unused optional sections, reconcile the form with the final protocol and privacy plan, insert required institutional language, and obtain IRB/REB approval. If your institution supplies a mandatory template, use that template and treat this download as a planning and completeness aid.

Build one process from several controlled components

A workable system includes more than the participant information and signature page:

1. Approved materials. Maintain the current approved version, date, language, and ethics-board approval record.
2. Discussion. Specify who may conduct it, when it occurs, what must be explained, and how questions are handled.
3. Decision interval. Provide sufficient opportunity to consider participation without pressure; avoid inventing a universal waiting period.
4. Comprehension check. Use open questions or teach-back where appropriate rather than asking only, “Do you understand?”
5. Documentation. Record the correct version, signatures, dates, person conducting the discussion, copy provided, and witness or representative requirements.
6. Ongoing consent. Define how new information, amendments, risks, or participation changes will be communicated and when re-consent is required.
7. Withdrawal. Explain how participants can stop and what may happen to data or samples already collected, subject to the protocol and applicable requirements.

A polished form cannot rescue an untrained discussion, and a good conversation cannot compensate for an obsolete document.

What information should participants receive?

Exact required elements are jurisdiction-specific. Teams commonly need to address:

• that the activity is research;
• the study purpose and why the individual is invited;
• procedures, visits, duration, randomization, masking, and experimental aspects;
• foreseeable risks, discomforts, and burdens;
• expected benefits, including when direct benefit is uncertain;
• relevant alternatives;
• confidentiality and its limits;
• authorized access to records;
• costs, payments, reimbursement, and research-related injury provisions where applicable;
• study, rights, and injury contacts;
• voluntary participation and withdrawal rights;
• future use, storage, sharing, or destruction of data and biological materials;
• investigator-initiated termination circumstances; and
• significant new findings that may affect willingness to continue.

Do not copy risk language from a related protocol without checking the final intervention, population, procedures, and evidence. Participant information should trace to the approved protocol, product information where applicable, risk assessment, privacy plan, and data flow.

Write for decisions, not institutional display

Understandable language is contextual. A grade-level target can be an editorial screen, but it is not a universal legal standard and does not replace testing with the intended population.

Use short sentences and familiar words; define technical terms; present decision-relevant information early; separate research from routine care; use consistent denominators for reliable risk estimates; avoid implying guaranteed benefit; and use headings, lists, tables, or diagrams when they reduce cognitive burden. Follow approved translation processes and address accessibility needs.

The objective is not a low readability score. It is a document and discussion that support a reasoned choice.

Protect voluntariness when the clinician is the investigator

IITs often arise from clinical practice. The person inviting participation may also provide care, creating a predictable power imbalance.

Separate clinical recommendations from the research invitation. Explain that declining will not compromise appropriate care. Avoid recruiting during acute distress when a meaningful choice is unlikely. Consider whether someone other than the treating clinician should lead or confirm the discussion. Review payments and reimbursement so they compensate fairly without obscuring burdens or creating inappropriate influence.

These are design decisions, not phrases to bury near the signature line.

Treat consent as ongoing

Build a trigger review into amendment management. Ask whether new safety information, procedural changes, alternatives, privacy changes, revised data use, or longer burden could affect willingness to continue.

For each change, document whether materials require revision, whether ethics approval is required before use, which active participants need notification or re-consent, how the decision will be recorded, and how superseded versions will be withdrawn.

TCPS 2’s framing of consent as ongoing is operationally useful even when another legal regime controls the study.

Electronic processes change the medium, not the obligation

Electronic approaches can support multimedia explanations, remote participation, version control, and audit trails. They can also introduce identity, access, privacy, accessibility, and support failures.

Verify governing requirements and ethics-board expectations. Define identity confirmation, question handling, signatures and timestamps, participant copies, downtime handling, and connection to source records. Clicking through screens does not demonstrate comprehension.

Pre-enrollment readiness check

Before approaching the first participant, confirm:

• the protocol and participant materials agree;
• correct versions and translations have approval;
• risks and alternatives are current;
• privacy, sharing, future use, and sample language match actual data flow;
• only trained, authorized personnel conduct the process;
• discussion and comprehension methods are defined;
• documentation and filing locations are clear;
• participants receive a copy;
• electronic systems have been tested;
• amendment and re-consent triggers are assigned;
• superseded versions can be identified and quarantined; and
• deviations can be detected, assessed, corrected, and documented.

Connect this workflow to downstream controls. The protocol should drive procedures and burden. Participant information should align with the case report form and data plan so the study does not collect information participants were not properly told about.

The practical standard

A defensible IIT process answers five questions:

1. Did the participant receive relevant information in an understandable form?
2. Was there a real opportunity to ask questions and decide voluntarily?
3. Did the team use and document the current approved process?
4. Did study changes trigger timely review of ongoing consent?
5. Can the investigator-sponsor demonstrate these controls without relying on memory?

If any answer is uncertain, improve the process before enrollment—not after a monitoring finding or participant complaint.

References

• ICH E6(R3), January 2025
• FDA Informed Consent Guidance, August 2023
• TCPS 2 (2022), Chapter 3
• Health Canada GUI-0100

---

Take the next step

An informed-consent form cannot be designed in isolation from the protocol, data plan, and operational workflow. Eye-Dea to Impact provides a practical framework for moving an investigator-initiated trial from idea through implementation and publication.