Our goal to remove hurdles to the development and implementation of innovative interventions extends to the entire translational continuum, and etiological biomarkers for age-related neurodegenerative diseases are the main use-case. Biomarkers consist of biological measurements that can detect a neurodegenerative disorder in vivo. They can potentially enable patient diagnosis, population screening, subject stratification for clinical trials, assessing patient response to new drugs, etc. However, to accomplish these tasks reliably, biomarkers must be validated under many respects, pertaining to the three main domains aiming to demonstrate Analytical Validity, Clinical Validity, Clinical Utility.
Demonstrating Analytical Validity means demonstrating that our measurement does assess the target biological anomaly, and that it does reliably. Experiments in this domain are close to basic research, however they need to use specific methods, like Standard Operating Procedures (SOPs), to collect such evidence consistently and enable all subsequent validation steps.
In the field of Analytical validity, our group is currently coordinating the definition and implementation of SOPs for cognitive assessment. Using these SOPs in memory clinics would improve at once the validation of biomarkers assessed on real world patients, and the reliability and cost-effectiveness of clinical diagnostic procedures.
This project was funded by the Swiss National Science Foundation (SNSF) and Alzheimer Forum Switzerland (AFS), and is being continued with the support of the European Alzheimer’s Disease Consortium (EADC) and the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Professional Interest Area (PIA) on Cognition.
Demonstrating Clinical Validity means providing evidence that our measurement can reliably detect the clinical disorder casued by the biological anomaly in patients. Many studies show this ability for biomarkers of Alzheimer’s disease (AD) and related disorders. However, they also contain many gaps, which prevents drafting evidence-based guidelines for clinical use. This is demonstrated by the fact that the official clinical guidelines (e. g., DSM-5) still do not incorporate biomarkers, and other guidelines are based on expert consensus rather than on formal evidence-to-decision procedures. Relative to this domain, we have developed a methodological framework spelling out the study design and critical outcome measures for many development steps, and keep taking care of updating this methodology to the evolving construct of AD and related disorders and providing clarifications helping researchers to comply with such framework.
Demonstrating Clinical Utility means providing evidence that using the biomarker is effective in improving patients’ health. This is the most challenging step, because it requires that the biomarker validation performed in clinical research comply not only with the “upstream” requirements of Analytical and Clinical Validity, but also with “downstream” requirements posed by regulators, health funders, health technology assessment, policy makers, as well as patients and other parts of our society. This part of the methodology is the object of current research plans. Ongoing tasks consist of importing methods from implementation science to define the methodology of specific implementation-related steps.
An ongoing overarching task consists of contributing to federate existing cohorts to make data FAIR (Findable, Accessible, Interoperable and Reusable) through the participation to the IMI-2 EPND project (European Platform for Neurodegenerative Diseases)