DISCUSSION
PD
We here present an up-to-date inventory of outcome measures for disease-modifying trials in PD based on expert and PPIE consensus. This inventory and framework will be used to guide the decision to select the outcome measures of the EJS ACT-PD MAMS platform trial, based on their fulfilment of desired criteria for an endpoint (e.g., validated, reliable, sensitive to change, acceptable) and their relevance to the intervention based on its mechanism of action and previously known effects (e.g., wet biomarkers as surrogate or direct markers of target engagement). When selecting and classifying the above measures as Core, Supplemental and Exploratory, a compromise had to be made between measures with the best clinimetric properties, acceptability to patients, feasibility, previous experience of use in PD trials, and regulatory considerations, which potentially might have led to prioritizing measures which appear less “promising” from a purely theoretical point of view (i.e., original validation study results) over others, to achieve an adequate balance and provide a realistic and practical tool. This work could also inform other trial initiatives aiming to identify disease-modifying treatments for PD and the framework used will allow updates with new emerging evidence in the future. However, this inventory of outcome measures was created as part of the development of a MAMS trial for progression of PD and as such, presents some particularities which might have influenced the final list of included outcomes. This type of trial requires large participant numbers across a variety of centers, and has a much longer duration than usual randomized controlled trials (RCTs) (i.e., several years) [Despite being included as exploratory due to the lack of formal validation in this setting, novel outcome measures, and especially digital endpoints, are a promising alternative to complement the currently available instruments. Their potentially increased sensitivity and the possibility of continuous monitoring in real-life conditions (i.e., at home) is likely to be a valuable addition to the administration of scales in the clinical setting. In line with this, a number of initiatives are looking into the clinical validity of these endpoints and their implementation in clinical research [The main strength of our approach was strong expert and PPIE consensus, embedding the patient’s voice into the development and recommendation of outcome measures, as well as evidence from literature reviews, information from other initiatives, and input from regulatory bodies.