Increasing Clinical Trial Efficiency with Continuous CRO Oversight
October 15th, 2015
By Rick Morrison, CEO and Founder Comprehend Systems and Bruno Gagnon, B.Pharm. MSc. Executive Consultant and former Clinical Operations Executive at BioMarin.
What is CRO Oversight?
This question is frequently posed by experienced managers. At minimum, it is essential to have the ability to tell a regulatory inspector that the CRO did what you hired them to do. At any given point of the project (and especially at the end when you tell the story of how the study was conducted) sponsor representatives must be able to explain that they know where they were in the project and how they got where they were supposed to go.
When the head of Clinical Operations says assertively “the study is going well” or “we are on target”, what does it mean?
Not only is it essential to know if the CRO is doing what they were hired for (are they performing against the Scope of Work?) you also want to assess if they are meeting your expectations for the quality of the work. This is why visionary ClinOps executives will develop Quality Agreements with their service providers. The challenge that remains is how to ensure you are following this Quality Agreement?
The amount of resources and, proportionally, the costs associated with CRO oversight is material. However, the size, global scope, and complexity of today’s clinical trials justify easily the need for sufficient CRO oversight. By visualizing and leveraging data coming from different sources in one central location in real time, we can dramatically increase sponsor resource efficiency. In other words, through better use of technology, sponsors can fulfill their needs in CRO oversight with a minimum amount of internal resources.
An emerging biotech company was conducting a phase 3 pivotal study in a chronic infectious disease. The study was expected to have 85 Sites and enroll 240 patients during a period of 9 months. They outsourced site activation, site management, patient enrollment, monitoring, data management and project management to their newly selected CRO partner. The clinical operations team assigned to this study was limited to a Clinical Trial Manager and a CRA.
With the right approach, access to critical data and a focus on key risks, this small team delivered a successful, on-time, on-budget trial. The four success factors were:
- Create a Quality Agreement with their CRO
- Create a CRO Oversight Plan
- Automate the key metrics in the Quality Agreement and CRO Oversight Plan
- Enable efficient, continuous, real-time collaboration
Creating the Quality Agreement and CRO Oversight Plan
The Head of Clinical Operations took the initiative of creating a Quality Agreement. According to the Avoca Group this plan “describes the standards, expectations and responsibilities of both Sponsor and CRO with respect to managing quality of outsourced clinical trials, clinical programs, or clinical functional services.” The next step was to develop a CRO Oversight plan: a step-by-step guide, with specific key indicators of performance or quality in order to continuously assess the CRO.
The following sections were included in this Sponsor’s CRO oversight plans:
- Site Initiation Success Rate
- Patient Enrollment and Retention
- Compliance with Monitoring Visit Schedule
- Visit Report Timeliness
- Compliance with Drug Accountability
- Database Error Rates
- Progress to DB Lock (Query Management)
- Trial Master File Reconciliation/Inspection Readiness
- Budget and Resource Tracking
- CRO Staff Turnover Rate
- Issue Resolution from Audit Findings
Automate The Plans
In order to use minimal resources with the maximum efficiency level, the setup of this project needed to be perfect. With the help of their technology partner, the team required access from aggregate data from all systems (EDC, IXRS, Central Lab, CTMS at the CRO). Then, they ensured they had visualizations (graphs and tables) that mapped to key metrics from the oversight plan.
The next steps were to set the thresholds and notifications: for example, if at any point in time, compliance with the monitoring schedule fell below 90%, an email notification was triggered to the CTM and this would initiate a conversation with the CRO PM to clarify the issue, investigate root cause and apply a corrective and preventative action as needed.
Since there was only a few FTEs working on this project, the Management Team including the Head of ClinOps also needed to have access to key metrics. So another part of the setup was to create an Executive Summary view (read this as a one-page dashboard to provide a quick view of the health of the project). Finally, before launching the automated system, a training was conducted with the fully integrated team between the Sponsor and the CRO.
How It All Comes Together: Efficient, Continuous, Real-Time Collaboration
Early in the project, site activation fell behind. For a number of reasons related to country regulatory approval, IRB/EC review, budgets and contracts, the CRO was unable to deliver according to the Quality Agreement.
Because the Sponsor had real-time access to operational data, the CTM was monitoring KPIs and was able to escalate quickly to their management. Focus changed to identify common obstacles and compare to sites who had been successful at getting activated. The team implemented some best practice and were able to accelerate the rest of the activation.
Patient enrollment was initially lagging but picked up nicely after critical mass of sites was increasing their screening effort.
Another issue that was of concern was a high level of eligibility deviations and some unexpected protocol exceptions (also called “protocol waivers”). These deviations are always a GCP inspection risk: as many sponsors have discovered the hard way, regulatory agencies around the world frown upon the granting of protocol waivers.
To remedy the situation, the Sponsor decided to organize a mid-study investigator meeting and retrain the site key personnel on how to better screen patients and increase the level of protocol compliance from beginning to end.
In this project, the CRO and Sponsor team had access to the same info at the same time. This allowed for ultimate collaboration; it set the tone for a culture of shared accountability and proactive problem solving.
With Quality Agreements and CRO Oversight Plans, Sponsors have the ability to compare where they are against where they should be (actual vs. planned). When the Clinical Trial Manager finds a problem, what does it look like? What should they do to address the issue? In our case study, the trial completed slightly ahead of schedule and results were positive. Because they kept clean project files, the post-study period (from Last Patient Out to CSR) was completed in record time. GCP Inspections were conducted at a few high enrolling sites and at the sponsor headquarters and a few observations were found regarding certain aspects of GCP compliance. However, the Sponsor was able to address the concerns with confidence and make a case that these issues would not be repeated in the future thanks to the implementation of corrective and preventative actions. Ultimately, the Sponsor was able to file with multiple regulatory agencies.
When time and resources are limited, technology is a powerful enabler of CRO oversight. Real time access to operational data gives both Sponsors and CROs alike a high level of confidence that the study is headed in the right direction. Technology is able to foster transparency and openness between Sponsors and CROs. Well documented and accessible quality agreements allow Sponsors to better set and manage expectations with their CROs. The ability to leverage technology to track performance against goals in real time is equally as important to a CRO who thrives on fostering productive and successful long term relationships with a Sponsor. With the right people, processes and systems as well as the basic principles described above, you can succeed and feel you have a healthy partnership with CROs and other service providers.