Clinical Trial Workflow | GMPify Training

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Clinical Trial Workflow - The GCP Framework for Human Subject Research

A clinical trial is a highly structured research activity governed by Good Clinical Practice, the international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve human subjects. ICH E6(R2) sets out the framework connecting protocol design, informed consent, investigator obligations, sponsor oversight, and data integrity into a single system whose purpose is protecting subject rights and safety while ensuring the resulting data is credible. This workflow map traces the trial lifecycle from startup through closeout, with the specific detail of SAE reporting, monitoring visits, TMF management, and protocol deviations each covered in their own dedicated map.

ICH E6(R2) GCP · 21 CFR Part 312 · EU CTR 536/2014 · ICH E2A

ICH E6(R2)

21 CFR Part 312

EU CTR 536/2014

ICH E2A

Phase I

First-in-human studies primarily assessing safety, tolerability, and dosing in a small number of subjects or healthy volunteers.

Focus: Safety, dosing, PK/PD

Phase II

Studies exploring preliminary efficacy and further characterizing side effects in a larger, more targeted patient population.

Focus: Efficacy signal, dose-finding

Phase III

Large-scale, pivotal confirmatory studies establishing efficacy and safety in a population representative of intended real-world use.

Focus: Confirmatory efficacy and safety

Phase IV

Post-marketing studies conducted after approval, monitoring long-term safety and effectiveness in broader, real-world use.

Focus: Post-marketing surveillance

Phase 1

Study Startup and Site Selection

1Develop the protocol and statistical analysis plan

Protocol developed defining objectives, design, eligibility criteria, and endpoints, together with the statistical analysis plan supporting the trial's conclusions.

ICH E6(R2)

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2Obtain regulatory and ethics committee approval

Protocol submitted for regulatory authorization and Institutional Review Board or Ethics Committee approval before any subject is enrolled.

21 CFR Part 312

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3Select and qualify investigator sites

Sites selected and qualified based on investigator experience, patient population access, and facility capability to conduct the trial per protocol.

ICH E6(R2)

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4Execute site initiation and personnel training

Site initiation visit conducted, training site personnel on the protocol, investigational product handling, and data recording requirements.

ICH E6(R2)

Phase 2

Trial Conduct and Data Collection

5Screen and enroll subjects

Subjects screened against eligibility criteria and enrolled only after documented informed consent is obtained.

ICH E6(R2)

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6Administer investigational product per protocol

Investigational product administered exactly as specified in the protocol, with accountability records maintained for every unit dispensed.

21 CFR Part 312

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7Collect and record data per GCP

Study data collected and recorded in the case report form accurately, completely, and in a manner traceable to source documents.

ICH E6(R2)

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Does an adverse event or protocol deviation occur during conduct?

YES → Initiate safety/deviation reporting NO → Continue per protocol schedule

Phase 3

Safety Monitoring and Quality Oversight

8Conduct ongoing safety monitoring

Accumulating safety data reviewed on an ongoing basis, with any emerging safety signal escalated for further evaluation.

ICH E2A

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9Perform monitoring visits

Sponsor monitoring visits conducted to verify source data, protocol adherence, and investigational product accountability at each site.

ICH E6(R2)

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10Conduct sponsor quality oversight and audits

Sponsor quality function conducts periodic audits of sites, vendors, and internal processes, independent of routine monitoring activity.

ICH E6(R2)

Phase 4

Trial Closeout and Reporting

11Conduct database lock and final analysis

Database locked once data cleaning is complete, followed by final statistical analysis per the pre-specified analysis plan.

ICH E6(R2)

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12Perform site closeout and IP reconciliation

Closeout visits conducted at each site, reconciling investigational product accountability and confirming all outstanding queries are resolved.

21 CFR Part 312

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13Compile and submit the clinical study report

Clinical study report compiled summarizing methodology, results, and safety findings, submitted to regulatory authorities as required.

ICH E6(R2)

Core GCP Roles and Responsibilities

Sponsor

Responsible for overall trial design, quality oversight, safety reporting, and ensuring the trial is conducted in compliance with the protocol and GCP.

ICH E6(R2)

Investigator

Responsible for conducting the trial at the site level, protecting subject rights and safety, and ensuring data accuracy and protocol adherence.

ICH E6(R2)

IRB / Ethics Committee

Responsible for independent review and ongoing oversight of the trial's ethical acceptability and protection of subject welfare.

ICH E6(R2)

Safety Event Escalation Steps (Overview)

Step 1 - Identify and assess the event Investigator identifies the adverse event and makes an initial assessment of its seriousness and relationship to the investigational product.

Step 2 - Notify the sponsor per required timeline Serious adverse events reported to the sponsor within the timeline specified by the protocol and applicable regulation.

Step 3 - Sponsor evaluates for expedited reporting Sponsor evaluates the event against the investigator's brochure to determine whether expedited regulatory reporting is required.

Step 4 - Notify the IRB and other sites as applicable Relevant safety information communicated to the IRB and, where applicable, to other participating sites.

Step 5 - Full detail covered in the dedicated SAE Reporting map This overview sits alongside a dedicated SAE Reporting map covering the complete detailed pathway and timelines.

Essential Document Categories (Overview)

Before trial initiation Protocol, investigator's brochure, regulatory and IRB approvals, and signed investigator agreements, all filed before the first subject is enrolled.

During trial conduct Updated approvals, monitoring visit reports, and safety reports filed continuously as the trial progresses.

After trial completion Final reports, closeout documentation, and IP accountability records filed to complete the trial master file.

Full detail covered in the dedicated TMF Management map This overview sits alongside a dedicated Trial Master File map covering complete document-level requirements.

Clinical Trial Quality Elements

Informed Consent Process Documented process ensuring subjects understand the trial's risks and benefits and voluntarily agree to participate before any study procedure begins.

Investigational Product Accountability Complete, traceable record of investigational product receipt, dispensing, and return maintained throughout the trial.

Source Data Verification Case report form data verified against original source documents to confirm accuracy and completeness.

Risk-Based Monitoring Monitoring intensity and focus scaled to the specific risks of the trial, rather than applying uniform monitoring regardless of risk profile.

Data Management Plan Defined plan for data collection, cleaning, and query resolution, supporting a reliable and traceable trial database.

Protocol Deviation Management System for identifying, documenting, and assessing the impact of any departure from the approved protocol.

Safety Reporting Timelines Defined timelines for reporting adverse events and serious adverse events to the sponsor, IRB, and regulatory authorities.

Trial Master File Complete, organized collection of essential documents demonstrating the trial was conducted in compliance with GCP and applicable regulation.

Never do this

Enroll a subject before documented informed consent is obtained. Administer investigational product without a complete, traceable accountability record. Allow a serious adverse event report to slip past its required timeline. Treat monitoring visit findings as informational without follow-up on required corrective action.

GCP vs GMP

Good Manufacturing Practice governs how the investigational product itself is manufactured, tested, and released. Good Clinical Practice governs how the trial using that product is designed, conducted, and reported. Both apply to the same investigational product at different points in its journey to and through a clinical trial.

Sponsor vs CRO responsibilities

A sponsor may delegate specific trial-related duties, such as monitoring or data management, to a Contract Research Organization. Regulatory responsibility for trial oversight and compliance remains with the sponsor regardless of delegation, making sponsor oversight of the CRO's performance an ongoing obligation.

Key regulations

ICH E6(R2) - Good Clinical Practice framework and roles. 21 CFR Part 312 - Investigational New Drug application requirements. EU CTR 536/2014 - EU clinical trial regulation. ICH E2A - clinical safety data management definitions and standards.