The Informed Consent That Was Signed Twice
During a pre-inspection file review at Site 12 for a Phase III cardiovascular outcomes trial, you find a consent form for Subject 1042 dated 3 March. The subject's screening visit was 1 March. The ICF version in the binder is v3.0, approved by the IRB on 15 February. But the site's regulatory binder also contains a partially completed v2.0 consent for the same subject, dated 1 March, with the subject's signature but no investigator signature and no date in the "person obtaining consent" field. The site PI explains: "The coordinator started with the old form by mistake, realized it, and had the subject re-sign the correct one two days later. The subject was fine with it." Subject 1042 was randomized on 10 March and has completed the study. She is one of 38 subjects at this site. The coordinator who handled the consent left the site four months ago.
1. Is this a protocol deviation, a consent violation, or both - and what is the regulatory significance?
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Both, and the distinction matters.
- Consent violation: The subject signed an obsolete form (v2.0) at screening. The IRB had superseded v2.0 on 15 February. Using a superseded form means the subject was consented with information the IRB no longer approved - that is a failure of the consent process itself, not just paperwork.
- Protocol deviation: Screening procedures (1 March) occurred before valid consent was documented (3 March). Any procedure performed for the study between 1 and 3 March was done without documented informed consent.
Regulatory significance:
- Under ICH GCP E6 and 21 CFR 50, informed consent must be obtained before any study-related procedure. The two-day gap is not a technicality if screening procedures (blood draws, ECG, history) occurred in that window.
- The missing investigator signature and missing "person obtaining consent" field on v2.0 mean you cannot establish who consented the subject or that a qualified person did it.
- This is likely a reportable protocol deviation to the IRB and sponsor, and potentially a finding at inspection. Whether it rises to "serious noncompliance" depends on whether the subject was exposed to risk without consent - document the screening procedures performed on 1 March.
Do not minimize it because the subject "was fine with it." The subject's retrospective comfort is not consent.
2. How do you scope the problem across the site, and what corrective actions follow?
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Scoping - the one-subject finding is a red flag, not the finding:
- Audit all 38 consents at Site 12 against the IRB approval log: which version was in force on each consent date? Any consent signed within the version-change window (mid-February onward) is suspect.
- Check the version-change window across all sites. If v3.0 rolled out 15 February, every site that consented subjects between 15 February and receipt of v3.0 has exposure. This may not be a Site 12 problem.
- The departed coordinator means you cannot interview the person who did it. Reconstruct from documents: training logs, delegation log, whether she was delegated to obtain consent, and whether the PI was involved at all.
Corrective actions:
- Report the deviation to the IRB and sponsor with a root-cause statement.
- Re-consent any currently enrolled subject consented under an obsolete version (none here - all completed - but check other sites).
- Retrain site staff on version control and the consent process; require PI sign-off on consent documentation going forward.
- Address the systemic gap: how did the site have v2.0 available on 1 March? Was v3.0 distributed and acknowledged? If the sponsor's rollout failed, the CAPA belongs to the sponsor, not the site.
Judgment point: The PI's casual framing ("the subject was fine with it") is itself a finding - it suggests the site does not understand that consent is a regulatory event, not a courtesy.