GCP compliance checklist for clinical trial teams (ICH E6 R3 edition)

Good Clinical Practice (GCP) is the international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials. ICH E6(R3), the latest revision, emphasises a quality-by-design approach, risk-based monitoring, and proportionate oversight — but the foundational compliance requirements remain as rigorous as ever.

Whether you are a clinical research associate, site coordinator, sponsor representative, or monitor, having a reliable GCP compliance reference helps you stay inspection-ready and protect participant safety and data integrity.

Informed consent — the non-negotiable foundation

• Consent must be obtained before any study procedure — including screening assessments — is performed.
• The process must be voluntary: no coercion, no undue influence, and adequate time for the participant to decide.
• The consent form must be written in lay language the participant can understand.
• Re-consent is required whenever the protocol, investigational product information, or known risks change materially.
• The consent form must be signed and dated by the participant (or legally acceptable representative) and the person conducting consent.
• A copy must be given to the participant and retained in the site files with an audit trail.

ALCOA documentation principles

• Attributable: every entry must identify who made it — initials, signature, or electronic identifier.
• Legible: handwritten entries must be readable; corrections must not obscure the original value.
• Contemporaneous: data must be recorded at the time of observation, not reconstructed from memory later.
• Original: first records are source documents; copies must be certified and traceable to the original.
• Accurate: data must reflect what actually happened — no assumptions, no rounding without justification.
• ALCOA+ adds: Complete (no missing required fields), Consistent (no contradictions), Enduring (durable media), Available (accessible for inspection).

Essential documents — what must be in your Trial Master File

• Before study start: protocol and amendments, IB and updates, sample CRF, ethics committee approval, regulatory authority approval, investigator CV and GCP training records.
• During study: all protocol amendments, updated IRB approvals, SAE reports and regulatory notifications, monitoring visit reports, delegation log, lab normals and certifications.
• After study close: database lock documentation, CSR sign-off, final drug accountability, destruction certificates.
• ICH E6(R3) emphasises that essential documents must support reconstruction of the trial's conduct — not just be filed for compliance.

Risk-based monitoring — the ICH E6(R3) shift

• E6(R3) moves away from prescriptive 100% SDV toward centralised statistical monitoring plus targeted on-site review.
• Sponsors must define critical data and critical processes — those whose errors would most affect participant safety or data integrity.
• Centralised monitoring should include statistical analysis for outliers, missing data patterns, and protocol deviation clustering.
• On-site monitoring is still required at appropriate frequency and depth — it is not eliminated, just proportioned to risk.
• All monitoring decisions and deviations from the monitoring plan must be documented and justified.

Inspection readiness: the core questions regulators ask

• Can you show when and how each participant gave informed consent?
• Are all protocol deviations and violations documented, assessed for impact, and reported where required?
• Does the data in the EDC match the original source documents (SDV)?
• Are training records current — does every team member have documented, in-date GCP training?
• Is your TMF complete, current, and organised so that a regulator can reconstruct the conduct of the trial?
• Are SAEs identified, assessed, and reported within the required timelines?