As recounted in part one and part two of “Uncommon Patient Recruitment Strategies in Alzheimer’s Disease Clinical Trials”, clinical trial enrollment in early phase Alzheimer’s disease (AD) clinical trials imposes heavier management burdens due to the number of clinical sites and cohorts, or groups, of patients enrolled per site. Part one of this series reflected on clinical trial enrollment challenges such as sluggish recruitment that can result from overburdened clinical site personnel, while part two discussed how Worldwide Clinical Trials began to develop a technology assisted cohort optimization strategy to reinvigorate recruitment and ensure efficient patient enrollment strategies.
In the third and final part of this series, we examine Worldwide’s uncommon technology assisted cohort research design as evidenced by the recent conduct of two separate Phase I, double blind, placebo-controlled Alzheimer’s clinical studies designed to establish the safety and tolerability of both single and multiple ascending dose(s) of blinded active drug in patients across similar single ascending dose (SAD) to multiple ascending dose (MAD) settings.
A total of 80 patients for the first clinical study, and a total of 57 patients for the second study, were enrolled across 10 dose-ascending cohorts for each study. Screen failure rates were 54% and 45%, respectively. For the first study, Alzheimer’s patients were enrolled across 12 sites in the US and Europe, while patients were recruited from nine clinical sites across five countries in Europe for the second study.
Access to Neurological Imaging and Cerebrospinal Fluid Sampling Expertise Critical to Site Selection
For both early phase Alzheimer’s disease clinical trials, the main objective was to assess the safety and tolerability, and pharmacokinetics across SAD and MAD cohorts. Having appropriate Phase I facilities and experience, access to neurologic imaging centers, and familiarity with cerebrospinal fluid (CSF) sampling procedures were critical factors in the site selection process for both of these Alzheimer’s clinical studies.
One primary challenge shared by both of these studies was related to the method of cohort management and escalation requirements. The complex cohort research design of two component sub-studies (SAD and MAD) resulted in the implementation of Worldwide’s unique clinical trial enrollment strategy to support study screening and enrollment activities and direct escalation to subsequent cohorts.
Importantly, in one of the studies, patients were able to transition from the SAD to the MAD cohort; and in the other study, patients that discontinued early were replaced, rendering accurate tracking via IRT obligatory. In both early phase Alzheimer’s disease clinical trials, the project team worked closely with the interactive response technology (IRT) staff to program and successfully leverage the technology necessary to support these trials, permitting vigorous and competitive patient enrollment to occur across multiple sites simultaneously, and importantly providing an equal opportunity to enroll patients across selected cohorts.
Cohort transition was determined by a series of programmable criteria based upon the unique protocol requirements. Medical monitoring staff were responsible for authorizing dosing of patients within a cohort via electronic approval, while the project management staff were responsible for the activation and closure of given cohorts based upon the outcome of each safety review meeting via IRT. The combined efforts across all functional groups and implementation of this technology facilitated continuous early phase study management in which recruitment into a fixed cohort of patients could be controlled centrally across multiple site locations.
One key factor in the successful implementation of Worldwide’s IRT-assisted cohort optimization strategy can be attributed to the speed and accuracy of data collection as well as efficient cohort management. The project team created a streamlined, effective process specifically tailored to these early phase Alzheimer’s disease cohort studies that was designed to facilitate an ongoing review of patient eligibility on the part of the study medical monitor.
Information was gathered from various data sources and compiled for easy review and confirmation of patient status. Ongoing details were provided to ensure patient wellbeing was maintained throughout the treatment period. Routine contact with sites coupled with a rolling data review resulted in the successful achievement of having over 90% of data clean at all times. This in turn permitted timely scheduling of the intra-cohort safety review meetings, saving even more time. Notably, a detailed written cohort design and management plan supported
- – protocol compliance,
- – the realistic opportunity for enrollment of eligible patients across sites,
- – the consistency in patient visits,
- – and importantly the optimization of the management of the various cohorts, saving time and costs while safeguarding patient safety and quality.
Worldwide Successfully Optimizes Early Phase Alzheimer’s Disease Clinical Trials
The ability to facilitate uninterrupted clinical trial enrollment across multiple sites in early phase Alzheimer’s disease clinical studies resulted in a continuous screening process, alleviating disruption in momentum and recruitment fatigue in cohort studies. The use of Worldwide’s IRT-assisted cohort optimization strategy:
- – allowed each site an equal opportunity to enroll patients,
- – decreased burden upon sites by providing a tiered screening approach, and
- – allowed for more accurate study planning and clinical research preparation for both patients and caregivers (i.e. accommodation for travel plans/vacations).
Safety and data review committee functions were also managed more effectively within this technology driven cohort design, yielding high quality data while minimizing review timelines and transition between cohorts.
In summary, Worldwide’s uncommonly elegant technology-assisted cohort optimization strategy detailed above resulted in faster progression through cohorts while preserving study data integrity in early phase multi-center Alzheimer’s disease studies, saving both time and money.
Thank you for reading the three-part blog series on Worldwide’s unique approach to early phase Alzheimer’s disease clinical trials. Our medical, scientific and operational experts look forward to speaking with you developing unique approaches to solving your complex challenges in clinical trial research.