This white paper will discuss the importance of risk-based monitoring and CAPA in clinical research within the context of the
following initiatives by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA):
■ 2013 Guidance: The release of a document titled “Guidance for Industry: Oversight of Clinical Investigations—A Risk Based
Approach to Monitoring” signaled the agency’s intention to maximize its oversight of clinical trials. The guidance
encourages the industry to use risk-based approach in monitoring clinical trials, as well as wider use of alternative
monitoring approaches, such as the use of centralized monitoring (e.g., remote monitoring conducted by statisticians
and data management personnel) instead of putting too much emphasis on on-site monitoring. The FDA recognizes
the dramatic increase in the number of clinical trials and greater complexity of those trials. Since it’s impossible for
the agency to inspect every clinical trial, the guidance is meant to ensure appropriate oversight through effective
monitoring2.
■ Clinical Trial Transformation Initiative (CTTI): This program is designed to identify practices that would
improve the quality and efficiency of clinical trials. It was initiated based on a partnership created in 2007 by the
FDA and Duke University. The CTTI has identified QbD, a risk management approach from the pharmaceutical
manufacturing sector, as a strategy that could increase data integrity and improve the quality of clinical trials. The
CTTI has been conducting QbD workshops for clinical research stakeholders, including sponsors, regulators, clinical
investigators, patient advocates, and academics.3 Quality by design, as promulgated by quality expert Joseph M. Juran,
is a systematic approach to close quality gaps, resolve quality issues, and prevent quality failures from the get-go. He
advocated quality planning, quality control, and quality improvement. In a nutshell, Juran believed that if you plan
and integrate quality from the earliest phase—design and planning stage—you will be able to avoid or at least minimize
quality problems later on4.
■ EMA’s Reflection Paper on Risk-Based Quality Management in Clinical Trials: The EMA, which serves as
a hub for regulatory agencies in European Union member states, released the reflection paper in 2011 to facilitate the
development of a more systematic risk-based approach to quality management of clinical trials and to promote Good
Clinical Practice principles and standards. The document identified current problems such as increasing globalization
of clinical trials, which complicates the regulatory and business environment for these clinical trials. It proposed
approaches that should commence at the earliest stage of a study. Without mentioning the term QbD, this document
encourages the identification of risks as part of the basic design of the clinical research (for every protocol throughout
the life of a clinical trial), which is essentially QbD’s goal.5