Clinical Quality Systems & the Outsourced Model
By Deborah Formelio
The landscape of clinical trials is evolving. The changes that are happening are due to the increased number of FDA-regulated trials, as well as a rise in the complexity of clinical protocols. As these protocols are becoming increasingly intricate, the need for highly functioning clinical quality systems is even more important.
Quality systems were originally a construct of Good Manufacturing Practice (GMP). However, regulatory authorities now expect that clinical trials are governed by efficient and practiced quality systems with respect to Good Clinical Practice (GCP).
Most Sponsors utilize services from Contract Research Organizations (CROs) to effectuate some or all of their clinical trial activity. While delegating responsibilities to CROs may be the most efficient model for some Sponsors, the Sponsor is still responsible for ensuring the trials are being executed in a safe, accurate, and reliable manner. The most common deficiencies noted regarding Sponsor and CRO oversight are as follows:
- Inadequate monitoring
- Failure to secure Investigator compliance
- Failure to notify the FDA, Investigators, and/or Institutional Review Boards (IRBs)
- Unqualified monitors aspect
Specifically, regulatory authorities have consistently and regularly cited Sponsors and CROs for deficiencies in the following categories concerning clinical quality systems:
- Personnel roles and responsibilities
- Standard Operating Procedures (SOPs)
- Quality assurance
- Document control
- Risk management
Clinical quality systems play a critical role in the Sponsor’s oversight and the CRO’s operations. The aforementioned deficiencies can be avoided via thoughtful planning that is prompted and required by efficient quality systems. Clinical quality systems mitigate risk in a number of ways, including:
- Standardizing processes and procedures
- Ensuring adequate training on procedures
- Defining roles and responsibilities, including escalation processes
- Establishing vendor management plans
- Standardizing integrated plan requirements, such as project plans, safety plans, monitoring plans, data management, etc.
- Establishing Quality manuals
- Defining and adhering to audit schedules and plans
When delegating tasks to a CRO, a common misconception is that the Sponsor has also delegated ultimate responsibility of the integrity and quality of the data. This fallacy has led to many FDA observations/findings. Sponsors should maintain a basic clinical quality system that serves as a foundation for overall strategy and management of their clinical trials. Even with the use of a CRO, the Sponsor should have a vendor management plan that includes selection and oversight of critical service vendors. The Sponsor is responsible for selecting an appropriate CRO with adequate clinical quality systems to manage elements under their purview, and designated in the transfer of obligations.
In the past decade, the FDA has made great efforts to emphasize the importance of quality systems in clinical trials, including the formation of the Clinical Trials Transformation Initiative (CTTI). The group is now comprised of several agencies such as the National Institutes of Health (NIH), the Office of Human Research Protections (OHRP) and other industry representatives. The core commitment and mission of the organization is to develop and implement practices that will increase the quality and efficiency of clinical trials among all stakeholders.