In clinical trials of preclinical Alzheimer’s disease (AD), participant characteristics, outcome measures, assessment procedures, and the context of assessment require substantially different strategies and procedures than those applied in clinical trials of symptomatic AD. Many of the tests and scales used commonly to measure cognitive change in symptomatic AD lack the sensitivity to capture the subtle changes that can occur in preclinical AD.
New approaches to the assessment of clinical trial outcomes are required to optimize studies for detecting the earliest disease-related changes and to measure the potential benefits of treatment with new investigational drugs.
Understanding the Preclinical AD Period
Clinical pathological models have provided methods and consensus criteria to allow identification of AD up to 30 years before dementia can be classified clinically. This is known as the preclinical period. People with preclinical AD are cognitively unimpaired (CU), and do not typically have concerns about their memory or thinking.
To address the unique population of CU adults in preclinical AD, new instruments such as the ADCS Preclinical Alzheimer’s Cognitive Composite (PACC) have been developed and refined.
Recently, a digital version of the PACC has been developed and implemented. This digital PACC has shown to be valid for clinical trials and is being used in pivotal trials of experimental anti-amyloid drugs in preclinical AD. The digital design streamlines distribution, training, and data quality. It also allows use of the PACC in remote supervised contexts, increasing flexibility for large late phase trials.
Three neuropsychologist share trial considerations from decades of work in preclinical AD in this whitepaper > Accurate Clinical and Cognitive Measurement in Preclinical Alzheimer’s Disease: Understanding and Addressing Unique Participant and Procedural Challenges
Validated Digital PACC Leverages Predictive Power & Reduces Burden
Just like conventional clinician-administered cognitive tests, digital tests of cognition can be bundled into a sensitive PACC battery for detection of the very early signs of AD-related cognitive changes. Based on decades of experience in cognitive science, Cogstate developed a digital PACC that substitutes conventional paper scales with digital scales within the same cognitive domains.
The digital PACC has demonstrated validity for use in in-clinic assessment contexts as well as for remote, supervised administration contexts. The equivalency of data arising from these different modes of administration has been presented at CTAD, AAIC, and AD/PD meetings and we invite you to follow the hyperlinks to access that data.
The digital PACC is particularly well-suited for clinical trials in the preclinical stage of AD where patient populations are typically younger, healthy, active in their jobs, communities, or families and often very busy. The facility to conduct some- or all the clinical assessments in remote, supervised contexts provides a low-burden solution for participants that can help reduce attrition rates.
In addition to remote administration benefits, the Cogstate digital PACC offers important operational advantages including repeatability without practice effects, culture-neutrality, and suitability for deployment in studies with a global footprint.
The digital PACC features real-time data monitoring and quality control. It is also easy to administer without the need for expert clinicians, thus reducing financial and operational costs for rater training.
Finally, digital cognitive assessments help address the FDA mandate for increased enrollment of diverse patient populations. Remote testing options can enhance study reach into additional geographic areas and facilitate enrollment of diverse patient groups who either reside outside of immediate catchment areas of clinical sites or lack transportation. Furthermore, as remote assessment requires fewer raters, expert raters from diverse cultural or linguistic backgrounds can be made available to study sites in various locations or countries.
In short, the Cogstate digital PACC—now being used in late phase trials in preclinical AD—helps address the challenges of conventional PACCs, minimizing rater training costs, reducing patient burden, improving patient diversity, and providing valid and reliable results.
