Early phase Alzheimer’s disease clinical trial recruitment can be viewed as an athletic event. There are frequent and intense efforts followed by a lull in the action as clinical trial site staff are called upon to repeatedly commence and halt their patient recruitment efforts.
And like athletes who get worn out after similar exertions, site staff can feel exhausted, suffering from what’s known as recruitment fatigue. The downside of fatigue in the field of play is more errors and even injury; but when clinical staff get tired it often causes sluggish patient enrollment in early phase trials and decreases the chance for a win in pharmaceutical R&D.
Overlooking Potentially Eligible Patients During Early Phase Recruitment
Compounding this weariness for clinical trial site staff is the frustration that comes when potentially eligible patients – many of them familiar faces – are actually overlooked due solely to the timing of enrollment or other procedural delays. This interruption in patient recruitment and inability to randomize every eligible patient often results in poor and variable enrollment at a site that cannot be forecasted accurately.
This is part one of a three-part series on an uncommonly innovative patient recruitment strategy that Worldwide Clinical Trials introduced in an attempt to invigorate sluggish Alzheimer’s clinical trial recruitment.
Possibility of Delay Multiplies in Clinical Trial Cohort Studies
The lack of accurate forecasting caused by patient recruitment and randomization interruptions noted above complicates study execution and contributes to delay. The possibility of delay traditionally increases in early phase Alzheimer’s disease clinical trials because the populations are usually spread across multiple sites.
These early phase studies are sometimes referred to as cohort studies as they are characterized by a relatively small number of subjects being enrolled at each dose, or cohort, across one or more clinical sites.
For example, a single ascending dose (SAD) study will classically enroll subjects in four to six independent cohorts in a sequential manner with each cohort being initiated following completion of data review at a certain time point of the current cohort; while a multiple ascending dose (MAD) study may require even more cohorts.
Seamless Transition Sought for Early Phase Alzheimer’s Disease Clinical Trial Cohorts
More recently, there has been an effort led by innovative clinical researchers to ensure a seamless transition from single to multiple dose cohorts (SAD-MAD) within a single study often consisting of up to 10–12 cohorts across as many sites. Of note, some sites may be engaged early on in the patient enrollment process while others are activated in a staggered approach.
Unlike clinical studies seeking to enroll healthy volunteers at a single site, the majority of early phase cohort studies in patient populations are conducted across multiple sites, as noted above, with the number of sites being dependent upon sample size, length and complexity of the study, and the recruitment potential of the indication of interest. This complex cohort design is often employed in early phase Alzheimer’s disease clinical trials.
Patient Recruitment Strategies: Guaranteeing Randomization and Avoiding Over-Enrollment
For early phase patient studies, it is common for multiple sites to be engaged in the simultaneous enrollment of patients into a single cohort study. Therefore, it is imperative to ensure the accurate and timely assignment of patients into each cohort while guaranteeing that all screened eligible patients for clinical study participation are actually randomized, and that there is no chance of over-enrollment.
This requires the centralized monitoring of rapidly changing patient recruitment efforts and notifying clinical trial sites of fluctuating accrual speed and limits in real time. This monitoring may involve moving some patients from screening to randomization, holding others back, and opening/closing recruitment across multiple sites simultaneously. Clearly, there is a high potential for confusion and recruitment fatigue.
Interactive Response Technology for Early Phase Patient Recruitment Strategies
In an effort to improve the experience of patients and the staff completing these patient recruitment tasks in early phase Alzheimer’s disease clinical trials, Worldwide Clinical Trials considered introducing a technological solution such as interactive response technology (IRT), which enables:
- • proactive management of patient enrollment/randomization,
- • dosing/drug dispensation,
- • clinical supply logistics, and
- • drug inventory management, unblinding, etc.
This technology includes interactive voice response systems and interactive web technology, which uses the internet instead of the phone as a gatekeeper and data tracker, with obvious advantages in terms of speed, accuracy and ease of use.
In early phase drug development there are multiple strategies which may be employed to help ensure successful cohort study conduct, with all of these strategies requiring a high level of data tracking and operational acumen. In order to be both efficient and successful, a unified approach must be undertaken not only to ensure that timelines are met but also that the study enrolls appropriate patients and yields high-quality data. Each cohort study therefore requires a well-defined and unique strategy which can leverage enhanced technology to ensure:
- • rapid and proper patient recruitment,
- • the seamless collection of data, and
- • accurate scheduling of safety review meetings – complete with relevant outcomes1.
The initial evaluation of the competing pressures in early phase Alzheimer’s disease clinical trials and the potential resolution using technology formed the basis of what became Worldwide’s unique cohort optimization strategy.
- Morissey, M., Roberts, R., O’Gorman, B., Wells, D. Applying New Technology to Randomization, Cohort Management and Dosing in Multicenter Early Phase Trials. Applied Clinical. Trials, Jan 15. 2015.