Assess and Mitigate Risk in Clinical Trials

Editor’s Note: This article is part of a series examining popular peer-reviewed articles from years past called “Peer-Reviews Revisited: Why You Should Read Today.” You can read the other articles in this series here.

Regulatory authorities routinely inspect clinical trials, sites, sponsors, investigators and other relevant parties to ensure compliance with good clinical practice (GCP) guidelines. Problems are often found.

The Food and Drug Administration has noted that the most common deficiencies by clinical investigators are failure to follow the investigational plan, protocol deviations, inadequate record-keeping and inadequate accountability for the investigational product. Deficiencies by trial sponsors and monitors include inadequate monitoring, failure to bring investigators into compliance and inadequate accountability for investigational product.

“In view of the significant impact of noncompliance on public health, medical science and long-term viability of companies, many sponsors put in place preventive plans to enhance GCP compliance and reporting, said Demissie Alemayehu, PhD, Vice President, Department of Statistics, Pfizer, and Adjunct Professor of Statistics, Columbia University, New York. “A quantitative approach to risk assessment and mitigation involves use of statistical techniques to select relevant risk factors with high predictive values of studies or sites that may be prone to noncompliance.”

Dr. Alemayehu was lead author for a quantitative assessment of clinical trial risks and mitigation techniques to enhance GCP compliance. The technique uses retrospective data collection and analysis to identify potential risk factors. Retrospective findings help plan prospective data collection to identify risk factors that can be addressed to mitigate risk.

Typical strategies include:

• Instituting measures to focus resources on highest-risk studies and sites.

• Monitoring visits aimed at instituting and reinforcing remedial measures in collaboration with site personnel.

• Proactive study design changes that reduce the potential for questionable GCP practices or frank violations in future trials.

“The quantitative approach can be extended to minimizing protocol deviations in trials,” Dr. Alemayehu concluded. “Protocol deviations and violations can have implications on study outcomes and interpretation of results. It is advisable to prospectively mitigate the problem.”