Site-independent confirmation of subject selection for CNS trials: ‘dual’ review using audio-digital recordings

摘要

Background Site-independent review of subject eligibility for central nervous system (CNS) trials has been used as a surveillance method to enhance the integrity and precision of the subject selection process. We evaluated the utility of a customized review strategy that employs site-independent review of audio-digital recordings of site-based screen interviews. Methods We applied a customized site-independent subject selection strategy in nine phase II double-blind, placebo-controlled clinical trials across the CNS spectrum. The Clinical Validation Inventory for Study Admission (C-VISATM, Boston, MA, USA) was developed as a site-independent review method that evaluates and confirms diagnoses, symptom severity, and subject validity prior to enrollment (randomization) into a clinical trial. The C-VISATM method uses audio-digital recordings of actual site-based interviews conducted at the screening visit. The recordings of these interviews accompanied by digital notes are electronically submitted for independent review and ‘dual’ scoring of key rating instruments. A multi-tiered system of site-independent reviewers either affirms subject eligibility or identifies administrative and/or clinical issues that may preclude study eligibility (screen failure). Results In this meta-analysis, 404 of 2,515 submitted C-VISATM eligibility reviews (16.1%) were challenged by tier 1 reviewers and escalated to a tier 2 reviewer. After telephone adjudication with the respective trial site investigator, 168 of these 404 tier 2 reviews (41.6%) were not approved yielding an overall screen fail rate of 6.7% for all C-VISATM submissions. The primary reasons for screen failure were insufficient documentation to support the intended diagnosis, symptom severity that did not meet protocol criteria, the presence of excluded comorbid conditions, and potential confounding factors that might obscure assessment during the trial. Conclusion The C-VISATM review process coupled with dual independent scoring of key rating instruments is a quality assurance strategy that provides a systematic site-independent eligibility filter to enhance the precision of subject selection and the integrity of study data. The C-VISATM strategy has broad applicability across the CNS spectrum because it achieves the objective of confirmatory site-independent review without producing excessive site or subject burden.