Beaufort Insights: ExL’s Clinical Quality Oversight Forum
In view of ExL’s upcoming 7th Clinical Quality Oversight Forum in Philadelphia, Beaufort quality oversight thought-leader John Wilson offers insight into some of the industry’s hot topics.
How will the revisions to the ICH E6 GCP Guidelines affect clinical quality oversight?
Revision 2 will have significant impact on quality oversight. It is important to note that there has not been a revision to ICH E6 since June 1996. Thus, when ICH goes to the effort to approve an addendum, it stands to reason that the addition is significant. With Revision 2, ICH is essentially requiring quality oversight:
- 5.2.1 “The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf.”
It is clear that sponsors cannot simply point to their quality control and quality assurance efforts in this regard. The old version of ICH E6 has always required QA and QC:
- 5.2.1 “A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control.”
The additional language in Revision 2 can only mean that sponsors now will need to demonstrate oversight above and beyond standard QA and QC practices. Regulatory authorities will be looking for a documented, unbiased and objective assessment of the vendor CRO work effort.
Independent quality oversight is a cornerstone for Beaufort. We provide our quality oversight clients with solid documentation including a quality oversight plan listing the key processes for assessment along with methods and timelines. We also provide two reports of hard metrics. An internal report, compiled on a regular basis that contains a comprehensive, quantifiable analysis of high risk issues, is used to drive early process improvement, CAPA and provide management with real-time metrics. A second report is used during FDA inspections to demonstrate exactly what the sponsor, through third-party quality oversight, did to ensure that the CRO provided its services according to contractual and regulatory requirements.
What is the difference between clinical QA and quality oversight?
Quality oversight differs considerably from QA and should not duplicate standard QA practices. Quality oversight is about processes and adherence to contractual and regulatory requirements. It is not about co-monitoring or re-auditing the study.
There are three distinguishing characteristics between clinical quality assurance and quality oversight:
- Clinical QA assures the integrity of the clinical data. Quality oversight provides an assessment of how a CRO is performing relative to requirements, standards, and expectations.
- Clinical QA is conducted as an assessment at one point in time. Quality oversight is performed over the course of the trial and allows for real-time early process improvement and CAPA.
- Clinical QA is provided by the sponsor as a function within the organization. Quality oversight involves an independent organization, thus providing a totally objective assessment of the CRO work effort.
Third-party quality oversight provides an independent assessment of CRO and other vendor performance, resulting in opportunities for early process improvement and resultant cost and time savings.
How does vendor oversight change between the strategic partner, preferred provider and functional service provider models? What remains the same?
It is important to take into account which service provider model a sponsor is using in order to prescribe the best approach to vendor oversight.
In a strategic partner or preferred provider model, where a long-term relationship exists between a sponsor and its clinical trial CRO, a “familiarity bias” may exist that makes it difficult for the sponsor to adequately assess the vendor CRO’s performance. In these models vendor oversight is best executed by a third party.
In a functional service provider arrangement, while it is much less likely that familiarity would interfere with objectivity, there remains the new requirement to provide and document active vendor oversight. In this, all three models remain the same.
Risk-based monitoring has become increasingly complex. Will it continue to grow in complexity or will the pendulum eventually swing back to a simpler approach?
The answer is a bit of both. It is important to understand that the requirement is for a risk-based approach, not necessarily a complex algorithm of percentages of certain data points to monitor, for example. After performing a risk analysis, some sponsors still will choose 100% source data verification. This isn’t the same as choosing not to do a risk-based approach. Rather, their risk-based approach led them to conclude that 100% SDV was appropriate for a given trial. Others, after going through the steps of a risk analysis, determine that a more structured, less-than-100% SDV approach is optimal for a given trial.
So it is not a matter of whether the pendulum swings toward more or less SDV. What is important is that all sponsors engage in a risk-based approach in this decision making.
How can sponsors and CROs be prepared for change–whether it be in regulations, staff turnover, M&As, or other changes both anticipated and unanticipated?
My best advice: Know the regulations inside and out. Also, trust your people and the process. We have found the most successful clients are those who are systems dependent and work within a framework that ensures efficient and effective processes.
It is also critical to demonstrate active oversight. Having an effective QO program in place is important, but equally important is working with a CRO like Beaufort that has a comprehensive understanding of the regulatory environment, that is supported by a highly qualified team, and that has a proven track record of successfully managing clinical trials. Bringing skilled people to the table ensures more accountability, more flexibility and more continuity even in the midst of a changing landscape.
John R. Wilson Jr., PhD, MPH, is senior vice president, Clinical Development and Quality Solutions, at Beaufort where he is responsible for Beaufort’s quality oversight and clinical trial monitoring practices. John has worked in the health care industry his entire career and has broad-based experience in clinical research and pharmaceutical manufacturing, regulatory strategy and compliance, and quality management.