TARGETED ELIGIBILITY REVIEW CAN DECREASE THE NUMBER OF INAPPROPRIATE PARTICIPANTS ENROLLED IN CLINICAL TRIALS

Background

Ensuring enrolled participants meet all the inclusion criteria and none of the exclusion criteria is critical to the success of any clinical trial. Regulatory agencies have historically deferred to the investigators’ determinations on whether a patient is appropriate for a clinical study; however, with the rise of clinics specializing in research rather than patient care, investigators’ motivations for enrolling participants may not always align with the best interest of science. Additionally, there are increasing examples of patients enrolled into trials where standard protocol defined screening procedures and review alone were not enough to ensure the quality of patients enrolled. The complexity of study designs and more robust eligibility criteria have created an environment where more sponsors are looking for additional oversight measures to ensure quality patients are enrolled. To mitigate and reduce the impact of the above-mentioned points, targeted eligibility review utilizing independent medical reviewers has started to become more common in clinical trials.

Objective

To evaluate the impact of targeted eligibility review on participant enrollment in psychiatric trials over the past four years and to analyze the reasons for screen failure.

Methods

Retrospective review of internal study enrollment trackers and targeted eligibility submissions across multiple psychiatric indications was done for over 1000 participants whom sites intended to randomize. Analysis was done comparing all patients who passed the first set of protocol defined screening criteria, as determined by the site, to those patients who were subsequently determined not to meet targeted eligibility criteria.

Results

We reviewed targeted eligibility data for 1332 participants across multiple trials and psychiatry indications. Since these participants’ screening information had already been reviewed by the investigators, and the investigators determined they were eligible to be randomized, all of the participants should have been able to proceed to Baseline. Upon further targeted eligibility review, 156 participants (11.7%) were determined to be screen failures prior to becoming randomized. While the combined analysis revealed an impact of ~12% more participants being screen failed after passing the investigators’ initial screening, this quality impact was observed to be as high at 38% in one individual study where the enrollment criteria were more complex. The overall impact of screen failing these additional patients was at its simplest a proactive reduction in protocol deviations. Additionally, targeted eligibility review may have potentially reduced a negative impact to the statistical analyses of these trials since these participants would have likely needed to be removed from ITT power calculations.

Conclusion

Incorporating targeted eligibility review in psychiatry clinical trials can reduce the risk of enrollment deviations. Further analysis is needed to determine the full impact on data quality.