GCP Compliance & Clinical Trial Management Hub

Essential elements include: study purpose and procedures, risks and benefits, alternative treatments, confidentiality protections, compensation for injury, voluntary participation, right to withdraw, contact information for questions, and any costs to subjects. All elements must be in language understandable to the subject.

Major deviations: May impact subject safety, data integrity, or study validity (e.g., wrong dose, missed safety assessment). Must be reported to IRB and sponsor immediately. Minor deviations: Administrative errors with minimal impact (e.g., visit window violations). Report according to protocol-specified timelines.

SAEs must be reported to the sponsor within 24 hours of awareness. Fatal or life-threatening events require immediate (same day) notification. IRB reporting varies but typically 7-15 days for related events. Always check your protocol and local requirements for specific timelines.

Source documents must be original records that can independently verify the occurrence of events. They should be contemporaneous, attributable, legible, complete, and accurate. Examples include medical records, lab reports, ECGs, and pharmacy logs. All entries must be dated, timed, and signed by the person making the entry.

Key requirements include: proper storage per label instructions with continuous temperature monitoring, accurate accountability records (receipt, dispensing, return, destruction), secure storage with limited access, expiry date monitoring, and proper documentation of any temperature excursions or other issues.

The delegation log should include: staff member's name and title, specific study responsibilities delegated, qualifications/training documentation, signature and date of delegation, PI signature authorizing delegation, and dates when responsibilities begin and end. Update promptly when staff responsibilities change.

Preparation includes: reviewing the monitoring plan and previous visit reports, organizing all study documents by subject, ensuring source documents are complete and up-to-date, preparing subject accountability summaries, reviewing any outstanding queries or action items, and briefing staff on the visit agenda and expectations.

This constitutes a major protocol deviation. Immediately notify the sponsor and IRB, document the finding thoroughly, follow sponsor guidance regarding continued participation or withdrawal, ensure subject safety is maintained, and implement measures to prevent similar occurrences. The subject's data may still be included in safety analyses.

Best practices include: complete CRFs promptly after each visit, ensure all data is transcribed accurately from source documents, use only approved abbreviations, leave no fields blank (use N/A when appropriate), respond to queries promptly with proper documentation, and maintain a clear audit trail for any corrections.

All staff must have: current GCP training certification, protocol-specific training, training on study procedures they'll perform, appropriate professional qualifications for their role, and documentation of all training in their training files. Training should be completed before study responsibilities begin and refreshed regularly.

Initial IRB approval is required before study initiation. Continuing review must occur at intervals not exceeding one year. All protocol amendments, consent form changes, and safety reports must receive IRB approval before implementation (except for safety measures to protect subjects). Maintain current approval letters and track expiration dates carefully.

Essential documents include: protocol and amendments, IRB approvals, informed consent forms, investigator agreements, delegation logs, training records, subject screening/enrollment logs, source documents, SAE reports, monitoring reports, drug accountability records, and correspondence with sponsors/regulators. Documents must be maintained before, during, and after the trial.

PIs must have: appropriate medical/scientific qualifications, current medical license (if applicable), GCP training certification, relevant clinical experience, adequate time to conduct the study, and access to sufficient qualified staff and facilities. All qualifications must be documented with current CVs, licenses, and training certificates.

Randomization must follow the protocol-specified method using validated systems. Blinding must be maintained throughout the study except for safety emergencies. Emergency unblinding should only occur when knowledge of treatment is essential for subject care. Document all unblinding events with justification, date, time, and personnel involved.

ALCOA+ principles: Attributable (who, what, when), Legible (readable), Contemporaneous (recorded when performed), Original (first recording), Accurate (correct and complete), Complete (all data captured), Consistent (no contradictions), Enduring (preserved for retention period), Available (accessible when needed). All data must meet these standards.

All recruitment materials require IRB approval before use. Screening procedures must follow protocol inclusion/exclusion criteria exactly. Informed consent must be obtained before any study-specific procedures. Special protections apply for vulnerable populations (minors, pregnant women, prisoners, cognitively impaired). Document all screening activities and consent discussions thoroughly.

Use current normal ranges provided by the performing laboratory. For central labs, use their provided ranges. Document any changes to normal ranges during the study. All lab reports must include normal ranges and be reviewed by qualified personnel. Flag clinically significant abnormal values per protocol requirements and follow up appropriately.

Document all concomitant medications with drug name, dose, frequency, start/stop dates, and indication. Review against prohibited medications list regularly. Ensure adequate washout periods before study entry. Any changes during the study require protocol review for potential interactions or effects on study outcomes. Report any prohibited medication use as protocol deviations.

Study closure requires: completion of all subject follow-up, resolution of all data queries, database lock, return of investigational products, final monitoring visit, submission of final reports to IRB and regulators. Archive all essential documents per regulatory requirements (minimum 2-25 years depending on jurisdiction). Maintain archive access and environmental controls.

All electronic systems must be validated before use with documented evidence of proper functionality. Systems must maintain audit trails, data integrity, and security controls. User access controls and authentication are required. Regular system maintenance, backup procedures, and disaster recovery plans must be documented. Changes require validation and change control procedures.

Maintain continuous inspection readiness through: regular self-audits, complete and current documentation, staff training on GCP principles, prompt resolution of monitoring findings, implementation of corrective and preventive actions (CAPAs), and maintenance of essential documents. Conduct mock audits and address any gaps proactively.

Types include: SAE reports (24 hours to sponsor), SUSAR reports (expedited to regulators), pregnancy reports (within 24 hours), DSUR (annual safety updates), and follow-up reports. Each has specific timelines, formats (often CIOMS forms), and recipient requirements. Maintain tracking logs and ensure complete follow-up information.

Sponsors are ultimately responsible for trial conduct and subject safety. They may delegate specific functions to CROs through written agreements but retain oversight responsibility. Key sponsor duties include: protocol development, safety reporting, monitoring, regulatory submissions, and ensuring GCP compliance. Delegation agreements must clearly define responsibilities and oversight mechanisms.

Medical device studies follow ISO 14155 and MDR requirements. Key differences include: different regulatory pathways, device-specific risk assessments, operator training requirements, device accountability (vs. drug accountability), post-market surveillance obligations, and unique labeling requirements. Some GCP principles apply, but device-specific regulations take precedence.

Special protections for: Minors (parental permission + assent), Pregnant women (minimal risk requirements), Prisoners (independent advocate, minimal risk), Cognitively impaired (legally authorized representative). Each group requires additional IRB review, specific consent procedures, and enhanced safety monitoring. Additional regulatory approvals may be required.

GDPR requires: explicit consent for data processing, data minimization principles, pseudonymization/anonymization when possible, data subject rights (access, rectification, erasure), data protection impact assessments, and data protection officer involvement. Cross-border data transfers require adequate protection measures. Privacy notices must clearly explain data use and retention.

Remote activities require: protocol amendments or deviations documentation, appropriate technology validation, subject consent for remote procedures, data privacy and security measures, equivalent quality standards to in-person visits, and regulatory approval when required. Source data verification must maintain the same standards regardless of monitoring method.

Risk-based monitoring focuses resources on the most important data and highest-risk areas. Implementation includes: risk assessment during planning, central monitoring for trend detection, targeted on-site monitoring based on risk and performance, key risk indicators (KRIs), and adaptive monitoring strategies. Source data verification should be focused on critical data points rather than 100% verification.

A comprehensive DMP includes: database design specifications, data collection procedures, query management processes, quality control procedures, database lock procedures, data transfer specifications, audit trail requirements, backup and recovery procedures, and roles/responsibilities. The plan should address both paper and electronic data collection methods.

IMP management requires: secure storage with controlled access, continuous temperature monitoring with alarm systems, accurate dispensing records with double verification, complete accountability from receipt to return/destruction, proper labeling and expiry date tracking, staff training on handling procedures, and emergency contact procedures for after-hours issues. Maintain detailed logs of all activities.