While the ICH E6 addendum, (R2), is already in force in Europe, the FDA has yet to publish the final guidance here in the U.S. Sponsors and CROs alike have been evaluating, discussing and generally worrying about how to prepare for this guidance. The draft guidance sets out some key areas to focus on, but every pharmaceutical company must make considered decisions as to how to align their processes and automation with the guidance.
From a 2016 poll of clinical leaders from global pharmaceutical companies, more than 70% claimed that the ICH E6 (R2) guidance was a top priority for them, yet 90% said they were still using spreadsheets for oversight and collaboration – resulting in some cases delays of more than 6 months, cost overruns and failed inspections. Issues such as these were discussed in a previous Comprehend webinar, where a number of Best Practice steps were presented to help Sponsors and CROs find their way through the ICH E6 (R2) maze.
While every organization has its specific goals and hierarchy, the “12 Best Practice Steps to Operationalizing ICH E6 (R2)” can help them think through some of the key areas where alignment with regulations can be a challenging goal. With regard to the addendum, this means that areas such as risk management, Sponsor-CRO collaboration and oversight, and the use of automation, which all need to be addressed. In a recent Metrics Champion Consortium (MCC) presentation at last year’s Clinical Metrics Performance Summit, founder Linda Sullivan pointed out that pharmaceuticals should not only consider oversight at the study level, but also at the operational process level and executive level. Each of these concerns require a hard look at the steps pharmaceuticals are taking to reach database lock, while considering the requirements of the new addendum.
Understanding the Guidance
In the webinar, the FDA guidance for the addendum was spelled out, and then aspects of technology and process were aligned to help organizations identify where they may need to focus. In one example, sponsors said that often the executive and/or strategic arm of study design and vendor management operates separately from the operational side of the business. This can result in Quality Agreements, Vendor Oversight Plans and Data Transfer agreements that are either inconsistent with the actual study process, or in some cases, not even used. A Best Practice approach to rectifying this could be to “operationalize” the Quality Agreement. For instance, metrics agreed upon in the Quality Agreement are represented by automation shared by both the CRO and the sponsor, and all relevant data in the system is measured by those metrics. An additional benefit would be if the metrics were updated automatically by real-time data, and notifications of breaches were automatically distributed to appropriate team members. The good news is that this can be done today.
Linking Plans to Automated Insights
A key part of the webinar was defining the four areas where sponsors can apply automation to support the addendum. The first area was addressing Quality Agreements. Questions such as “Which metrics to focus on?,” “How do we easily create KPIs?” and “How can we monitor threshold breaches?” can all be resolved through automation. The creation of the CRO Oversight Plan is more process-related, but metrics can be assigned and measured to watch and manage areas such as data transfers and escalation paths. 73% of respondents to a poll agreed that the most difficult part of operationalizing to ICH E6 (R2) comes from aggregating and harmonizing data that needs to be reviewed, evaluated and reported on. When managing data from both in-house sources and external partners, sponsors are overwhelmed by both the complexity and the amount of time necessary to assess critical results. However, if the data can be integrated in a timely manner, and updated in real-time through automation, a huge part of this stress is alleviated. The key to not only a successful process, but also milestone achievement, is absolutely related to the use of visualizations of status, performance and progress. These are scorecards and dashboards for shared participants in the studies and portfolios. They are designed to provide the right knowledge to make insightful decisions early enough in the study phases to impact the success of the project.
Reaching the ICH E6 (R2) Goal
According to the webinar, once these areas have been defined, metrics and KPIs are built, data integration is well established, and users are ready and trained on the process, the 12 Steps to Operationalizing ICH E6 (R2) have been achieved.
For more details, please see our webinar and our Infographic on Operationalizing for ICH E6 (R2).