FROM CONCEPT TO TRIAL PLANNING

Incorporating this type of analysis in the clinical trial planning stage enables project teams to define operational boundaries on performance, set realistic time lines, and understand important trade-offs between the number of sites selected versus the number of monitoring resources needed to activate and manage those sites. This helps teams quantitatively identify improvement opportunities in their site selection and start-up processes. Then, when setting performance targets, we can invite all the stakeholders to go through individual parameters to reach consensus based on a common understanding, and align actions/resources to ensure total organizational support in reaching the performance targets.

For example, determining the targeted number of patients per site is generally about determining how many sites to use. PhESi's approach assesses the issue from the perspective of site activation and enrollment performance. We all know that high priority clinical trials generally obtain more resources and financial support. However, effectively utilizing those allocated resources is an entirely different issue. As we saw in the earlier example, more money and resources (applied to activating more sites over a longer period of time) did not, in fact, shorten the enrollment cycle time—instead it prolonged it.

If we were able to get data from several dozen clinical trials in a single indication and enroll the same number of patients in each trial, we could look directly at the relationship between the number of sites used and the performance of those sites using Average Site Enrollment Rate (ASER). In reality, we use number of patients per site (Total Enrollment Target/Number of Sites) as a surrogate to number of sites in trials with same enrollment target.

By doing so, we minimize the impact of clinical trials with different enrollment targets, and still are able to understand the impact of number of sites being used when other factors are equal. We found that when number of patients enrolled per site increases, we increase the performance of all the deployed sites in that clinical trial, as measured by Average Site Enrollment Rate (ASER). In other words, by adding more sites to a clinical trial, the result is a reduction in the average performance of the sites the sponsor has activated. If the same number of patients are allocated across MORE sites then each site enrolls fewer patients and the Average Site Enrollment Rate (ASER) goes down.

Sponsors can rely on this approach to find the "Sweet Spot", with just the right amount of sites to ensure targeted enrollment cycle time to maximize the value of available resources against "speed to market' projections. For example, when working on a respiratory disease clinical trial, we find the ASER for clinical trials with biological intervention to be 0.52, versus 0.83 for the clinical trials with small molecule intervention.

This difference is highly instructive to sponsors as it anticipates and reflects the higher level of difficulties for sites to enroll patients in clinical trials with biological interventions for a particular disease. That 60 percent difference between 0.52 and 0.83 is significant enough to guide the sponsor to commit to a larger number of sites being deployed in a biological trial, so that targeted enrollment cycle times can be achieved.

As these parameters are objective and specific, they are easily accepted by project teams and provides a measure of objective performance to senior management. In return, it effectively improves communication and understanding among stakeholders as to the ramifications of selecting more or fewer sites for example.

This approach also provides a structured framework to proactively detect as well as manage possible derailments in the execution of the trial. Root causes for these derailments can be identified in specific areas, such as site activation and/or site enrollment performance. Before merely adding on more sites, study teams can seriously evaluate whether it makes more sense to enhance the enrollment performance of the existing sites (using a variety of methods and approaches), deploy a site activation "SWAT" team to rapidly activate any new sites or at least understand the time line implications of following their traditional site activation process.

Did you Know?: ASSUMING THE COST TO ACTIVATE A SITE IS $20,000 (A REPRESENTATIVE YET CONSERVATIVE INDUSTRY ESTIMATE), NEEDING 160 MORE SITES IN CLINICAL TRIAL B COMPARED TO CLINICAL TRIAL A MEANS $3.2 MILLION MORE IN SITE ACTIVATION COSTS

Gen Li, PhD, MBA is president and founder of PhESi.HE can be reached at gen.li@phesi.com
. Beth Harper contributed to this article.