Benchmarking Protocol Deviations and Their Variation by Major Disease Categories

Abstract

Background Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience. Methods Nearly two-dozen companies provided the Tufts Center for the Study of Drug Development (Tufts CSDD) with data on the design and the performance of 187 protocols. Results The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial. Oncology clinical trials have the highest relative mean number of protocol deviations affecting more than 40% of patients enrolled in each trial. The number of endpoints, the number of procedures per visit, and the number of countries were modestly positively associated with and predictive of, the incidence of deviations per protocol. A strong positive relationship was shown between the number of investigative sites and the number of protocol deviations. Conclusion The results of this initial study provide useful measures that sponsor companies can use to benchmark their own protocol deviation experience, identify factors most associated with protocol deviations, and determine whether remediation is warranted.

Practical Guidelines for Standardised Resolution of Important Protocol Deviations in Clinical Trials Conducted in Sub-Saharan Africa

“…Deviations to randomisation, IP administration plans, and trial follow-up procedures required to assess primary trial endpoints are important deviations because they can significantly affect participant’s safety, well-being, and the reliability of key study data. Though these deviations can virtually occur in every trial, complex study designs, multiple study endpoints, the number of procedures per visit and the number of investigational sites have been positively associated and shown to be predictive of high incidence of protocol deviation in trials [ 27 ].…”

A framework for assessing clinical trial site readiness

“…They also may encourage greater institution-wide attention and investment in issues for which individual disease-specific investigators may have limited influence, such as contracting and IRB turn-around times. Applying the site readiness practices across individual sites of a multisite trial could reduce protocol deviations, which increase with the number of sites in a trial [22], by improving the standardization of training, infrastructure, and culture at disparate sites.…”