GCP for Sponsors - Module 3

GCP for Sponsors

Module 3: Monitoring & Oversight

This module describes how Sponsors maintain oversight of clinical trials, even when tasks are delegated to CROs or vendors.

Sponsor Oversight

SPONSOR

The Sponsor retains ultimate responsibility for trial conduct, participant safety, and data integrity…

…even when tasks are delegated to CROs, labs, or other service providers.

Monitoring, service provider management, audits

Oversight is achieved through quality control & quality assurance

Delegated service providers and investigator sites

Monitoring

Monitoring is the principal quality control activity and is carried out by a sponsor representative (Clinical Research Associate (CRA) or monitor)

Ensures compliance with the protocol, SOPs, GCP and applicable regulatory requirements

Oversees the progress of a clinical trial

CRA

Monitoring

Key activities:

CRA

Site selection and initiation

Line of communication between sponsor and sites

Reviewing essential records maintained by the site

Confirming eligibility and ensuring informed consent is obtained

Ensuring AEs/SAEs are reported correctly

Confirming the investigational product is stored, dispensed and destroyed correctly

Source Data Verification (SDV) and Source Data Review (SDR)

Identifying and reporting any noncompliance and/or protocol deviations

Site close out

Service Provider Oversight

Sponsor should ensure service providers have the necessary trial specific training and documents

Sponsor must demonstrate oversight

It’s essential that roles and responsibilities are clearly defined in agreements

CRO

ePROs

Lab

Starting at qualification

…continuing through ongoing review and audits

Risk-Based and Proportionate Approach

Objectives and endpoints

The extent and nature of monitoring should be based on identified CtQ factors and risks

Design and complexity

Current knowledge & safety profile

CRA

Risk assessment should determine the:

Frequency of monitoring

Investigational product

Blinding

Level of SDV

Sites requiring targeted visits

Number of participants

Risk-Based and Proportionate Approach

Not all service providers should have the same level of qualification and oversight

This will depend on:

• Impact on participant safety and rights

• Impact on data integrity and reliability

• Complexity and novelty of the service or technology

• Extent of subcontracting

• Service provider experience

• Ability to detect errors without service provider involvement

In our scenario, the ePRO used by the sponsor was for primary endpoint data; therefore, oversight levels should be increased

Identifying Noncompliance

Noncompliance can occur at any level – sponsor, service provider or investigator sites

As examples:

Protocol deviations

Missed visits, incorrect procedures, dosing errors

GCP noncompliance

Missing informed consent, inadequate source documentation

Safety reporting

Late SAE reporting, incomplete safety information

Investigational product

Storage excursions, accountability discrepancies, unblinding errors

Managing Noncompliance

A risk-based approach ensures there is a focus on significant deviations

Assess impact on participant safety, rights, and data integrity

Classify significance (e.g., minor vs important/serious)

Perform Root Cause Analysis (RCA) and implement Corrective and Preventative Actions (CAPA) proportionate to the risk

Serious Breach reporting requirements should be defined in a procedure (where applicable)

Monitor trends for systemic noncompliance

Increase monitoring or oversight where systemic issues are suspected

Independent Data Monitoring Committees

Reviews unblinded, accumulating data on behalf of the sponsor, allowing independent and data-driven oversight

Provides recommendations on:

Clinicians

PV Experts

Trial modifications (e.g., does levels)

Safety Concerns

Early efficacy

DMC

Biostatisticians

Checkpoint

• The role and responsibilities of a monitor

• Service provider oversight expectations

• Applying a risk-based approach and proportionality to oversight

• Identifying noncompliance and managing deviations

• Independent Data Monitoring Committees

End

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