Risk-based quality management (RBQM) isn’t something you merely add to an existing clinical trial. It must be integrated into each step of the process.

Think of it as building a house, explained Chrissy J. Cochran, PhD, director of the Office of Bioresearch Monitoring Operations at the FDA. “You wouldn’t start building a house with the second floor,” she told attendees at the recent WCG Avoca Quality Consortium Summit.

The basement is risk assessment, the ground floor is protocol development, and the top floor is the monitoring and quality assurance (QA) plan.

A Firm Foundation: Risk Assessment

A strong foundation begins with a comprehensive risk assessment. “That is what we really should be basing the foundation of all our clinical trials on.”

The “construction crew” should include more than the clinical operations team. Bring in other stakeholders who can offer valuable perspectives, she counseled. These include thought leaders, clinical investigators, and monitors. Find out how those managing data will be looking at a protocol and the data generated. Learn how those in charge of monitoring safety will consider risks.

By gathering these valuable perspectives early, sponsors can identify potential risks and develop effective risk-mitigation strategies. Ideally, this same crew of stakeholders will continue to provide insights during protocol design throughout the trial. This sort of early collaboration helps ensure consistency and reduces the likelihood of protocol deviations.

That’s why it’s important to involve monitoring and quality assurance staff in protocol development so there’s a strong framework when the time comes to create the monitoring/QA strategy.

The Ground Floor: Protocol Development

Engaging the same crew helps eliminate inconsistency, one of the most common problems the FDA encounters when inspecting protocols, she said. Too often, the narrative portion of the protocol conflicts with the tables listing the assessments that need to be done, the timeframes, the dates, etc. The FDA’s number-one finding for clinical investigators is failure to follow the protocol. “It’s easy to see how that can happen if our protocols are not internally consistent.”

Ensuring Quality

The top floor is monitoring and a quality assurance plan, and Cochran offered insights on how to ensure quality throughout the clinical trial process.

1. Create a system to support quality research

• Simplify protocol outcomes and assessments by contrasting what you’d like to know with what you absolutely need to know about the product’s safety and efficacy, which can reduce potential for error.
• Use technology to track, trend, and increase the visibility of errors so they can be dealt with in real time, such as case report forms (CRF) with built-in edit and logic checks.
• Standardize systems and formats where you can. Use standard definitions and validated instruments when possible.
• Keep protocol amendments to a minimum and check CRFs and consent forms against each amendment.
• Insist on training, and then test it.

2. Select qualified staff and ensure they receive adequate training and supervision

• Make sure each staff member is trained on the protocol, and regularly assess training to ensure it is effective.
• Verify staff members are fully qualified to carry out assigned duties. This means understanding different state requirements. For example, in some states, certain nursing licenses do not allow the holder to conduct physical exams.

3. Ensure the sites and investigators are a good fit

• Assess whether the sites have adequate equipment, time and resources to perform the trial adequately. How many staff members does the site have? How many trials are they already doing?
• Confirm that investigators possess relevant experience, training and skills related to the specific disease state and indication of the trial.
• Determine the investigators’ commitment to research. FDA investigators occasionally encounter a “clinician vs. clinical investigator” attitude during inspections. This can result a in failure to follow the protocol. “The protocol isn’t written in a way [a clinician] would normally treat their patients, so they try to do it in a way that flows with their clinical practice.” For instance, they don’t perform procedures in the right timeframe. That could lead to serious data collection issues.

4. Implement systems to detect and correct errors in real time

• Maintaining an audit trail is essential for effective risk management. Cochran emphasized the need for audit trails to be easily readable and interpretable by investigators. A clear and human-readable audit trail allows for efficient inspections and helps expedite the review process. “We will ask for audit trails. We do look at those,” she said. “We want to be able to go through them without having to refer… to a huge chart because everything is coded or in symbols. Having a clear audit trail that is human-readable will really go a long way to making your inspection go faster.”

Build the House

RBQM demands a systematic process for the assessment, control, communication, and review of risks to the quality of the product across its lifecycle – not just the lifecycle of the trial, but the lifecycle of the product.

We can help your organization build risk-based quality management into your next trial. WCG’s 360 Protocol Assessment™ provides a holistic view of a sponsor’s protocol to ensure quality. Our assessment incorporates strategies to proactively mitigate or manage the identified risks for faster clinical trial execution.