Clinical trial eligibility in PSP: Population representativeness and potential criteria adjustment based on PSP-NET findings

Parkinsonism Relat Disord. 2024 Dec 10:131:107226. doi: 10.1016/j.parkreldis.2024.107226. Online ahead of print.

Abstract

Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients.

Methods: we enrolled 221 PSP patients diagnosed according to the MDS clinical criteria. All patients were screened with a set of inclusion and exclusion criteria based on previous and ongoing clinical trials in PSP and underwent motor and cognitive evaluation with the Montreal Cognitive Assessment battery and the PSP rating scale, respectively. Then, clinical features of eligible and non-eligible patients were compared at baseline and after 15,93 ± 8,77 months follow up.

Results: Eligible (28 patients, 12,6 %) patients were younger, showed shorter disease duration and lower severity but similar distribution of PSP phenotype and disease progression rates compared to non-eligible patients. The most restrictive non-modifiable criteria were independent gait, disease duration and cognitive status. Willingness to undergo lumbar puncture and treatment stability for previous 60 days represented potentially modifiable criteria.

Conclusion: Overall, PSP eligible for clinical trials are representative of the general PSP population. While motor and cognitive impairment represent the most important non-modifiable barriers to enter a clinical trial, other criteria as willingness to undergo lumbar puncture and treatment stability are potentially modifiable. Specific strategies are discussed to increase the number of eligible patients working on potentially modifiable criteria.