Clinical meaningfulness refers to both the measurement of concepts of interest which are relevant for patients and to treatment effects which are sufficiently large, such they confer clinical benefit for patients. As outlined in a recent publication arising from the Alzheimer’s Association Research Roundtable, “determining whether an Alzheimer’s Disease (AD) intervention is clinically meaningful remains a challenge”.1
The authors, including Cogstate’s Chief Science Officer, Chris Edgar, note that, “demonstrating that treatments are clinically meaningful across the AD continuum is critical for meeting our goals of accelerating a cure by 2025.” They go on to elaborate a framework for which clinical meaningfulness must be established for clinical stage of disease: asymptomatic, prodromal, and dementia; and for each stakeholder i.e., patient, care partner, clinician, regulators, and payers and health economists.
One element of this is establishing thresholds for meaningful change at both the level of the patient (clinically important response) and group (clinically important difference).2.
This concept is further elaborated on in a recent publication in Neurology. Here, the authors describe how the use of anchor and distribution-based estimates for meaningful change have been applied to common neuropsychological tests in the Swedish BioFinder cohort study.
As a co-author, Cogstate’s Dr. Edgar notes, “results demonstrate how such methods might start to inform the field as to both the magnitude of change and difference that might be associated with clinical benefit, as well as those tests that might best predict functional benefit, in asymptomatic and prodromal stages.”
Ongoing research is expected to help establish parameters for clinical benefit across a range of outcomes targeting different parts of the AD spectrum, such as that presented at the recent AAIC meeting by Teng et al.3 Substantial progress is now being made to address a major challenge for the field which it is hoped will address both merging FDA Patient Focused Drug Development Guidance and inform our understanding of new AD therapies.4
Read the Publications:
- Rentz DM, Wessels AM, Annapragadad AV, et al. Building clinically relevant outcomes across the Alzheimer’s disease spectrum. Alzheimers Dement (NY). 2021.
- Borland E, Edgar CJ, Stomrud E, et al. Clinically Relevant Changes for Cognitive Outcomes in Preclinical and Prodromal Cognitive Stages: Implications for Clinical Alzheimer Trials. Neurology 2022
- Lansdall CJ, Teng E, McDougall F, et al. Selecting appropriate meaningful change thresholds for trials in early AD. AAIC meeting San Diego 2022