Quality by Design & Risk Management

The Sponsor-Investigator should use a proportionate and risk-based approach to quality management throughout all stages of the trial process.  This involves building Quality by Design into the trial design and protocol procedures, identifying Critical to Quality (CTQ), i.e. factors likely to impact participants safety, rights and well-being and reliability of the trial results, evaluating and controlling the risks, communicating the risks and controls, regularly reviewing the risk control measures and adjusting these controls as necessary.

A clinical trial is more likely to answer the research questions when the Sponsor-Investigator and their team have spent time developing the protocol design elements such as:

·              Study population – selection of appropriate eligibility criteria

·              Clear pre-defined study objectives

·              Approaches to minimise bias

·              Endpoints that are well-defined, measurable, clinically meaningful, and relevant to patients

 

Attention must also be given to operational criteria such as:

·              feasibility of conducting study

·              selection of suitable investigator sites

·              quality of testing facilities

·              quality of data management procedures.

Critical to Quality (CTQ) Factors are an identified set of factors relevant to ensuring quality of the trial and whose integrity is fundamental to the protection of trial participants, reliability and interpretability of the trial results, and the decisions made based on the trial results.

If the integrity of CQFs is undermined by errors of design or conduct, the reliability or ethics of decision-making based on the trial results would also be undermined.

The Sponsor-Investigator is responsible for designing quality into the trial and should identify the CQFs.  This should be done at the time of trial planning and involve a range of stakeholders to ensure you have identified all critical processes and data.  This includes patients and/or consumers with lived experience, members of the Central Coordinating Team (such as the trial biostatistician, trial data manager and clinical trial manager) and members of site team(s) (such as Investigators, study coordinators, research nurses).    

The identification of CTQ factors needs to be documented so the Sponsor-Investigator and Central Coordinating Trial team know what is critical for success of the trial.

To identify your CTF factors, start with the protocol and create a list of critical data and processes, i.e. those items critical to protection of participants, meeting the primary and secondary objectives,  operational delivery and any processes impacting GCP principles.

Once you have identified your CTF factors conduct a risk assessment to evaluate the likelihood, impact and detectability of errors related to those factors and strategies to mitigate/control these risks.  See Risk Management (below) for further information.

All MCRI-sponsored trials conducted under a CTN/CTA must implement a proportionate approach to the identification and management of risk that incorporates the following steps:

·              Risk Identification

·              Risk evaluation

·              Risk control

·              Risk communication

·              Risk review

·              Risk reporting

 

Refer to ICH GCP E6 (R3) 3.10.1 for further details about the requirements and Melbourne Children’s 
MCTC035 Template | Risk Assessment and Risk Management Tool for Clinical Trials for further guidance and the Risk Assessment & Management Plan template for documenting your approach to risk assessment and management for your trial. This plan should be reviewed regularly throughout the trial lifecycle and updated if/when there are any changes to the risk rating/controls.

CRDO runs two training courses that cover risk management in clinical trials.

These workshops are essential for anyone involved in risk management/assessment of MCRI-sponsored clinical trials.  Select the courses below for further information.


Monitoring investigator-initiated trials

Safety oversight, monitoring & reporting