Ensuring Uniform Protocol Revision Usage
in Multi-Site
Randomized Prospective Clinical Trials
Methodology
A multi-layered approach to the problem was adopted - traditional center communications and leveraging of the eRO capabilities afforded by the technology. Guidant formulated an internal and external communication plan, and sought the advice and services of MedNet to facilitate smooth, comprehensive rollout and utilization of the new protocol. A simplified overview is shown in figure 1.
Figure 1. Protocol Revision Process Overview
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The eRO web-based system ensured that Investigators had a 30 day warning period that a protocol revision was to be implemented on the "go live" date of 08 Dec 03, and instructed them on the steps to take to remain in compliance, namely to attest to the IRB status and forward the required documents to the sponsor in the required timeframe.
In essence, the system performed a status validation in the background as the user for a given site logged on to either enroll new patients or update data on existing patients. In addition a "flashing banner" was employed on the electronic CRFs to continue to draw users' attention to the upcoming required change. If a user did not come into compliance within the required timeframe, they were precluded from entering new patients into the study until they came into compliance. Figure 2 illustrates the flow process for the user of the system.
Figure 2. User Process Flow
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At each status check (i.e., at each login) before revision acknowledgment, the user would be given the opportunity to review and respond with IRB status and documentation thus -
Figure 3. Protocol Revision Status Form
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Users who failed to submit the required documentation within the requisite timeframe after acknowledgement were displayed the following advice regarding the outcome of post "go live" non-compliance.
Figure 4. Protocol Revision Documentation User Warning
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In addition, the real-time reporting capabilities provided by the eRO to the sponsor enabled daily monitoring of protocol-revision message viewing, acknowledgements, and likely compliance failures, which enabled them to focus field implementation efforts on problematic or tardy sites. The net effect of the methodology employed was that over 90% of sites began using the revised protocol within the required timeframe, and zero patients were erroneously enrolled under the provision protocol revision, as sites were precluded from doing so by the status validation checks used by the system. Delays to the research initiative were minimal post the "go live" date of 08 Dec 03 - as can be seen in the following chart, bearing in mind the downturn in enrollments over the holiday period was expected, and enrollments resumed at an increased rate in January 2004.
Figure 5. INTRINSIC RV Enrollments Over Time
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Conclusion
Protocol revisions are highly problematic in large multi-center clinical trials. Revisions in a paper-based system require a highly burdensome orchestration of multiple players and may result in significant delays to the research initiative. Use of a well-designed web-based data capture and management methodology such as that employed by MedNet Solutions and Guidant facilitates comprehensive and smooth communication and revision roll-out, and inherently precludes non-compliance.
© Timothy Pratt 2005
