When implementing Quality Risk Management (QRM) principles in Clinical Trials as described in ICH Guidance Documents (Q9, E6, E8) it is crucial to have a team of knowledgeable Subject Matter Experts (SMEs) who guide and inform decision-making throughout the clinical trial lifecycle. Their participation is essential for ensuring the safety of trial participants, data integrity and the viability of a clinical trial. Amarex SMEs can help in several ways:

Risk identification

Amarex SMEs help identify potential risks in the trial design phase, by:

• Leveraging 27 years of CRO/clinical trial experience across all indications to consider previously identified risks while reviewing current literature on the indication and study.
• Offering full-scope, specialized expertise in all CRO departments (e.g., Clinical Development and Operations, Regulatory Affairs, Safety and Pharmacovigilance, Biometrics, Data Management, IT Development, Medical Writing, Business Development, Quality Assurance).
• Collaborating extensively with Amarex Risk Manager using tools such as FMEA (Failure Mode and Effects Analysis) to create and maintain a comprehensive risk register for each Amarex Department.
• Goal: To identify any risks to your clinical trial that could meaningfully impact critical-to-quality factors before trial initiation and during the conduct of the trial.

Risk assessment

Amarex SMEs assess identified risks with the Amarex Risk Manager to:

• Compare newly identified risks with previous risk assessments in the Amarex Risk Register.
• Prioritize ICH E6 GCP quality concerns such as participant safety, data integrity, and regulatory compliance when defining a risk.
• Analyze newly identified risks according to FMEA criteria such as probability, severity and detectability using quantitative (and qualitative) scoring.
• Determine a Risk Priority Number (RPN) for each identified risk by combining scores for probability, severity and detectability.
• Goal: To maximize risk mitigation in your Amarex clinical projects through prioritization of resources.

Risk mitigation planning

Amarex SMEs contribute to the development of a study-specific Risk Management Plan (RMP) by:

• Ensuring that each Amarex Department identifies critical-to-quality study risk areas to monitor prospectively.
• Considering how to mitigate and monitor risks related to innovative trial designs, various study populations and study-specific technological considerations.
• Verifying compliance with applicable guidelines (ICH-GCP) and regulations e.g., (FDA and EMA) within each Amarex Department.
• Planning to reassess identified risks and risk evaluations as needed throughout the clinical trial.
• Goal: To improve clinical trial oversight and emphasize participant safety, data integrity and regulatory compliance at trial outset.

Ensuring GCP adherence through risk control and risk monitoring

During a clinical trial, Amarex SMEs:

• Mitigate identified risks during a clinical trial and inform key stakeholders on changes in the status of current risks, emerging risk trends, and new risks in their area of expertise.
• Host IDMC Meetings for Sponsors and provide input on any identified risks associated with adverse event incidence (safety signals).
• Manage tailored, risk-based monitoring methods (centralized, onsite and remote) to ensure participant safety, data integrity and protocol compliance.
• Support risk control with the establishment of quality tolerance ranges to trigger risk evaluations where applicable.
• Employ risk-based internal/external audits to identify deviation trends and conduct root cause analysis/CAPAs as necessary.
• Goal: To ensure risks are controlled throughout a clinical trial.

Risk review, communication and reporting

Throughout the clinical trial and at its conclusion, Amarex SMEs:

• Review knowledge and experience gained during the clinical trial to ensure that previously known risks remain controlled and new risks are identified and managed.
• Communicate the results of the Amarex study team’s risk review to relevant stakeholders as necessary and update risk register as required.
• Summarize and include description(s) of important quality issues and remedial actions taken in the Clinical Study Report.
• Review, approve and submit any required documentation to regulatory authorities.
• Goal: To ensure stakeholders remain informed on identified risks and mitigation efforts throughout the clinical trial.

Improvements for future clinical trials

Using QRM in a CRO environment, Amarex SMEs are well positioned to:

• Update the Amarex risk register based on lessons learned from previous clinical trials across the spectrum of indications.
• Improve clinical trial design, participant recruitment strategies, and clinical operations based on previous experience.
• Goal: To ensure that your clinical trial is managed in the most efficient and compliant manner.