Novel Approach to Movement Disorder Society-Unified Parkinson's Disease Rating Scale Monitoring in Clinical Trials: Longitudinal Item Response Theory Models.

BACKGROUND

Although nontremor and tremor Part 3 Movement Disorder Society-Unified Parkinson's Disease Rating Scale items measure different impairment domains, their distinct progression and drug responsivity remain unstudied longitudinally. The total score may obscure important time-based and treatment-based changes occurring in the individual domains.

OBJECTIVE

Using the unique advantages of item response theory (IRT), we developed novel longitudinal unidimensional and multidimensional models to investigate nontremor and tremor changes occurring in an interventional Parkinson's disease (PD) study.

METHOD

With unidimensional longitudinal IRT, we assessed the 33 Part 3 item data (22 nontremor and 10 tremor items) of 336 patients with early PD from the STEADY-PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine for PD, placebo vs. isradipine) study. With multidimensional longitudinal IRT, we assessed the progression rates over time and treatment (in overall motor severity, nontremor, and tremor domains) using Markov Chain Monte Carlo implemented in Stan.

RESULTS

Regardless of treatment, patients showed significant but different time-based deterioration rates for total motor, nontremor, and tremor scores. Isradipine was associated with additional significant deterioration over placebo in total score and nontremor scores, but not in tremor score. Further highlighting the 2 separate latent domains, nontremor and tremor severity changes were positively but weakly correlated (correlation coefficient, 0.108).

CONCLUSIONS

Longitudinal IRT analysis is a novel statistical method highly applicable to PD clinical trials. It addresses limitations of traditional linear regression approaches and previous IRT investigations that either applied cross-sectional IRT models to longitudinal data or failed to estimate all parameters simultaneously. It is particularly useful because it can separate nontremor and tremor changes both over time and in response to treatment interventions.

Informations de copyright

© 2021 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

Déclaration de conflit d'intérêts

The research of Sheng Luo was supported by National Institute on Aging (Grant R01AG064803). The Rush Parkinson's Disease and Movement Disorders Program is a designated Clinical Center of Excellent supported by the Parkinson Foundation. The authors have no conflicts of interest to report.