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The Illusion of Safety

by Craig Morgan
04Sep2017

Risk is our constant companion, and as clinical trials grow in complexity so do risk-based challenges to bring new therapies to market at an ever-increasing pace. The continued reliance on Excel, which lacks project- and risk management functionality has created an illusion of safety often fueling the rescue study industry.

The Illusion of Safety

To date, risk management efforts in drug development have focused mostly on post-marketing drug safety, but regulatory changes and competition are now emphasizing a risk-based management approach beginning with study startup (SSU). The Food and Drug Administration and the European Medicines Agency have released documents on greater acceptance of risk-based methodologies, which they state should begin from the start of a clinical trial.

In keeping with the regulatory trend toward identifying and mitigating risk, forward thinking industry leaders have been trading in their Excel spreadsheets, in favor of custom-built SSU applications that can automatically trigger workflows as a trial unfolds, ensuring country-specific regulatory and SOP compliance, as well as generating critical operational metrics.

Focusing on site selection and site activation (current gaps in the project manager tool kit), these new tools bring workflow-based processes to study teams, allowing both sponsors and contract research organizations to visualize key data in real-time and identify bottlenecks early on. Using quantitative data to perform intelligent site selection (i.e., relying on algorithms to weigh data sources) drives better site selection and reduces overall study risk. This technology mitigates risk factors for recruitment and retention by finding the optimum alignment of top-performing sites with substantial patient databases, and quickly assessing which sites have performed best in similar studies.

For site activation, such tools enable project managers to discover meaningful patterns in the data for tasks such as status of packages for the institutional review board (IRB), patient enrollment success, and receipt of study drug. Risk can thus be continuously tracked and mitigation strategies can be adapted much earlier in the decision-making cycle due to features such as: activity alerts, study team member assignments and role management, milestone tracking along the critical path (and milestone re-projection warnings), and real-time views of global study status (including anywhere, anytime access to study data). In support of risk mitigation activities, real-time alerts help project managers intervene immediately or before a major setback has happened, instead of after the fact. This is crucial, since in conventional SSU, intervention typically takes place after an issue has occurred, when it is too late to proactively avoid the problem.

The operational metrics associated with contracts (Figure 1 shows site level contracts tasks and milestones) – a notorious bottleneck in starting trails – illustrate this point. The All Contracts executed milestone normally available in an eTMF as a summary of artifacts does not provide the operational metrics which precede it (e.g., Site Budget ready to First Budget package send, Site Contract language ready to Last Contract language ready for approval, etc.) If the trial timeline is delayed, what caused the delay? The budget? The contract? Or maybe, the template? The reality is you would have no idea an issue even exists until after your planned date for All Contracts executed has elapsed, let alone what caused the delay and where to focus your process improvement efforts.

Operational metrics associated with site level contracts tasks and milestones

Figure 1: Operational metrics associated with site level contracts tasks and milestones

Research recently published on global site contract cycle times found that overall contract cycle times have doubled from an industry median of 1.5 months in 2009-2011 to over 3 months in 2014-2015. Contracts conducted in North America, traditionally a top performer, have increased from 1.3 in 2010-2011 to 2.4 in 2014-2015. Emerging markets continue to have longer cycle times. Additionally, Oncology trials typically have the longest site contracts cycle time compared to other therapy areas. The study evaluated 20,000 recently-executed contracts for Phase II/III trials from leading biopharmaceutical companies.

SSU represents a complex array of processes and without tools designed for risk management planning, each has potential for causing delays, and ultimately jeopardizing the study. To mitigate this situation, purpose-built SSU tools spanning site identification, feasibility assessment and activation that provide risk management capabilities are a critical improvement over traditional manual processes. Stakeholders can view elements in real time related to site performance, such as high patient availability, enrollment and retention, and critical cycle-time metrics, and take corrective action. This level of process improvement can help keep studies on track and within budget, and ultimately, speed new therapies to market.

Article originally published in CenterWatch, May 2017

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