A Practical Shortcut To Risk-Based Trial Management

By Patricia Santos-Serrao, Market Segment Manager, Global Pharmaceutical, Blood and Biologics at MasterControl

Clinical research is about generating reliable data to determine the safety and efficacy of medical products while at the same time protecting the rights, safety and well-being of participating subjects. To help clinical research organizations effectively manage trial sites, identify factors with the potential to compromise subject safety or protocol compliance and to smooth the trial process, the FDA released the “Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring” (August 2013). Shortly thereafter, the European Medicines Agency (EMA) issued its final version of “Reflection Paper on Risk-Based Quality Management in Clinical Trials” (November 2013).

Since that time, there has been a scramble to understand these guidelines and to implement them. Most companies don’t realize, however, that they already have a shortcut to risk-based clinical trial management on their premises—quality management.

Risk-based management addresses many of the same issues that are handled by an organization’s manufacturing and development arms. In fact, existing quality management practices may go further to mitigate risk and ensure quality and compliance, as well as speed trial time.

Utilizing Quality Management Principles in Clinical Trials

Manufacturing and quality already understand Corrective Action, Preventive Action (CAPA) principles. These practice areas already have systems in place to ensure protocol compliance, training, monitoring, continual re-assessment of priorities and CAPA. The clinical research arm of an organization often doesn’t understand that the same processes they need are being used in other functional areas of the organization. It is almost like it’s a well-kept secret as opposed to an asset.

Quality management for manufacturing involves designing protocols to not only reach the highest quality output, but also to reduce risk and handle deviations effectively when they arise. That is what is at the heart of CAPA—risk mitigation and management.

These same principles can be applied to clinical trial protocol design. Every protocol has areas of risk, where the likelihood of noncompliance or outright failure to follow procedures is greater. When you apply disciplines like CAPA to the design process, you design the trial in a way that mitigates risk, build an effective monitoring system and implement processes to efficiently handle deviations.

Here’s an example of how CAPA can be used in clinical trial design. Say there’s an investigational product that needs refrigeration to maintain quality and effectiveness. If the product is not stored properly or is left out on a counter, the resulting data could be compromised or the product could even become dangerous. When this condition is discovered under CAPA, a plan goes into play that would make an immediate corrective action (CA) to correct the problem, and then preventive actions (PA) would be implemented to prevent this issue from arising in the future.

Corrective action is driven by the answers to a number of critical questions. Was this a one-time situation or a chronic one? Was improperly-stored drug product administered to any patients? Actions could include quarantining the questionable products, implementing a monitoring plan for any patients who may have received this product and taking action to correct compromised patient data, such as excluding the data from the outcome or withdrawing the patient altogether. Longer term actions could include changing labeling to make storage protocols more visible, implementing more comprehensive training and reviewing protocols to ensure that storage is clearly delineated.

Building Quality into Clinical Trial Designs

Building quality systems into clinical trial design includes understanding where risk areas may exist. Does a certain investigational site have a history of sub-standard record keeping? If so, then what preventive actions should be taken to mitigate this risk?

Aside from issues of patient recruitment and compliance, common challenges to trial quality and outcome include investigator qualification, site qualification, past audit history, study staff training and study information location. A good risk management plan should take these factors into account, identifying where the risk is, putting monitoring and audits into place to catch deviations quickly, implementing a comprehensive training program and developing a solid CAPA plan.

Each clinical quality plan should address the study’s unique nature, nuances and procedures. It should include a quality assurance system that can easily capture the data, inform auditors and monitors of areas of risk and help study managers handle any CAPA events that arise. Training management and process management should also be implemented.

Going beyond clinical trial management systems to clinical trial quality systems will allow sponsors to quickly access and manage areas of risk throughout the life of a clinical trial. Adding quality principles borrowed from an organization’s manufacturing arm may help speed clinical trials and reduce the risk of failure.

Patricia Santos-Serrao is a Life Sciences professional with almost two decades of experience in regulatory affairs and clinical areas of the pharmaceutical industry. She is currently Market Segment Manager, Global Pharmaceutical, Blood and Biologics at MasterControl, a company that provides software solutions for quality and compliance to life science industries.