5. Ethics
Section 5 of a clinical study report confirms and describes how the people who took part in the study were protected. ICH E3 divides it into three subsections: independent ethics review, the ethical conduct of the study, and patient information and consent.
What Section 5 asks for
A person invited to test a medicine wants to understand, before agreeing, what will happen, what could go wrong, and whether they can change their mind. They also want someone independent of the study team to examine whether the research treats people fairly.
Section 5 explains these protections. It connects three questions: who reviews the study, which ethical principles govern it, and how participants make an informed choice. The section is brief, but the supporting work extends throughout the trial. Its short statements gain meaning from the independent review, understandable information, and documented choices behind them, and they give the ethical foundation for the study’s methods and results.
| Everyday question | E3 subsection |
|---|---|
| Who independently examines the study and its changes? | 5.1 — Independent Ethics Committee or Institutional Review Board |
| Which ethical principles guide the study? | 5.2 — Ethical conduct of the study |
| How and when do participants agree to take part? | 5.3 — Patient information and consent |
5.1 — Independent ethics review
An Independent Ethics Committee (IEC) or Institutional Review Board (IRB) examines research involving people to help protect their rights, safety, and well-being. The names differ between settings. The central role is independent ethical review, which is broader than checking that a consent form contains a signature box.
The protocol is the reference for ethical review. A protocol amendment is a formal change to that document. Ethical oversight covers changes as well as the starting plan: adding extra procedures or changing eligibility can alter what participation involves.
E3 asks Section 5.1 to:
- Confirm that the study and any amendments receive IEC or IRB review.
- Point to a list of all committees consulted in Appendix 16.1.3.
- Provide the committee chair’s name when the regulatory authority requires it.
Review and approval are distinct steps. E3 asks for confirmation of review. ICH E6(R3) also calls for documented approval or favourable opinion before trial initiation. A review can end in decisions other than approval. A CSR’s account should accurately describe the documented ethical oversight rather than treat submission for review as permission to proceed.
For a study conducted at several hospitals, the reader needs to know which committees cover the participating sites: one committee may cover several sites, or several committees may be involved. An appendix table can connect each committee’s name and location with the sites it covers, but E3 specifies the content of the list, not the design of a table.
A chair leads the committee. A list of committees is not a list of their members, and E3 does not request every member’s name.
5.2 — Ethical conduct of the study
E3 asks for confirmation that the study follows ethical principles originating in the Declaration of Helsinki. The Declaration is the World Medical Association’s statement of ethical principles for medical research involving human participants. Its principles concern respect for people, voluntary participation, protection from unreasonable harm, and responsible use of personal information. The Declaration addresses independent review, privacy, understandable information, and the right to decline participation or withdraw consent.
Three related concepts have different roles:
| Concept | Its role |
|---|---|
| Declaration of Helsinki | Ethical principles for research involving people |
| Good Clinical Practice | Provides the framework behind the title-page compliance statement |
| Applicable regulatory requirements | Requirements governing the particular study in its jurisdictions |
Section 5.2 asks for the Helsinki statement, not a paragraph-by-paragraph reproduction of the Declaration. The CSR’s account needs to reflect the study records and the standards applicable to that study; a general assurance does not replace an accurate account of important problems.
For example, a polished statement about ethical conduct does not explain an important failure in the consent process. The report then needs an appropriate factual account of the failure, with cross-references to the relevant discussion of study conduct. This follows from transparent documentation; E3 prescribes no additional subsection for it.
5.3 — Patient information and consent
Informed consent is the process through which a person receives relevant information, understands it sufficiently to decide, and voluntarily agrees to participate. The informed consent form (ICF) documents that decision. The conversation, the information, and the decision all matter. Voluntary means the person can decide without coercion or undue influence.
Consider a participant who signs a document without understanding that the study requires additional blood samples. The signature alone does not establish that the person understands what participation involves.
What the participant needs to understand
The detailed content of informed consent comes from broader guidance, including ICH E6, rather than E3’s two short paragraphs. Typical questions include:
- Why is the study being done, and which parts are research?
- What procedures, visits, and responsibilities does participation involve?
- What are the foreseeable risks, burdens, and possible benefits?
- What other treatment options are available?
- How is personal information handled?
- Who answers questions or helps if a study-related injury occurs?
- What happens if the participant stops treatment or leaves the study?
Clear, concise language helps make the decision meaningful.
How consent is obtained
E3 asks the report to describe how consent is obtained. A useful factual description identifies the process used: who conducts the discussion, how information is provided, how questions are addressed, and how agreement is documented. These details give substance to the word “how”; E3 does not prescribe a fixed sentence template.
Some studies involve people who cannot provide consent themselves. A legally acceptable representative is a person or body authorised under applicable law to consent on their behalf. Assent is the participant’s affirmative agreement when they cannot independently provide legally valid consent, as can occur with children. Applicable requirements and the participant’s abilities determine the process, and Section 5.3 describes the actual arrangement when it is relevant.
When consent is obtained
E3 explicitly asks for the timing of consent in relation to enrolment, the study’s defined point of entry, and gives pre-screening and allocation as examples. Screening assesses whether someone qualifies; allocation assigns a treatment, using the method described in the protocol.
The examples tell the writer to identify the actual sequence; they do not permit postponing required consent until treatment assignment. ICH E6(R3) establishes prior consent as the general expectation before trial participation and explains narrowly governed emergency arrangements. Where such an arrangement applies, the report needs to describe its specific approved basis.
For a fictional routine trial, the sequence may be:
- The team explains the trial and answers questions.
- The participant provides documented consent.
- The team performs screening procedures specific to the trial.
- Eligible participants enter the treatment-assignment stage.
A statement that “consent precedes dosing” can leave uncertainty about procedures performed before the first dose, and E3’s request for timing makes that sequence visible.
Consent also remains relevant after entry. Re-consent means obtaining consent again when appropriate—for example, when new information materially affects willingness to continue. ICH E6(R3) does not make every administrative change a reason to repeat consent.
Where the forms belong
E3 asks for representative written patient information, if any, and a sample consent form in Appendix 16.1.3. A sample form means the document’s content and structure; it does not mean reproducing every participant’s signed form.
Supporting documents such as ethics approvals and informed consent forms generally remain in the Trial Master File (TMF), which holds essential study documentation, rather than automatically accompanying the CSR. Documents needed to review the CSR, and those a particular country or region requires, still belong in the submission, and omitted documents must be available promptly on request.
| Material | What it establishes |
|---|---|
| Main Section 5 | Ethical review, conduct, and consent process |
| Committee list identified in 16.1.3 | Which IECs or IRBs are consulted |
| Representative information and sample form | What participants are told and how consent is documented |
| Underlying study records, including signed forms and approvals | Evidence supporting the account, retained and supplied according to applicable requirements |