Sample Size and Power Calculations Based on Endpoint Responsiveness: Applications to Trials of Disease-Modifying Therapies in Parkinson's Disease
- 1Indivi AG
Abstract
In Parkinsons disease (PD), early phase clinical trials of disease-modifying agents generally use the MDS-UPDRS Part III as the primary outcome measure of motor function, which typically requires a large sample and/or a long (12- 18 months) treatment duration, even if a substantial treatment effect is assumed. This is due to the rather slow rate of early PD progression relative to the variability of the MDS-UPDRS Part III assessments. Using placebo-arm data from four recent large Phase 2 trials of early-stage PD (SPARK, PASADENA, PADOVA and LUMA), the sample size needed to detect a range of assumed treatment effects on MDS-UPDRS Part III progression was estimated. The trial sample size estimates obtained for MDS-UPDRS Part III and for smartphone-based sensor-derived motor functional composite (MFC) endpoints were compared using an approach based on relative responsiveness to disease progression. The calculations were also implemented in an interactive, publicly accessible application. Powering a one-year trial using the MFC1 endpoint, derived from three active assessments (6-minute walk, U-turn and Hand Pronation-Supination), or the MFC2, which adds 60-Second Typing, was projected to reduce the required sample size by more than half relative to the MDS-UPDRS Part III, assuming equivalent proportional treatment effects.
Related
- Comparative efficacy and safety of targeted disease-modifying therapies in adults with primary IgA nephropathy: a systematic review and network meta-analysis
- The path to treating multiple-etiology dementia: Combining vascular risk control and disease-modifying neurodegenerative therapies
- Enhancing deep sleep with auditory stimulation to boost cognitive training responsiveness in people with Parkinson's disease and mild cognitive impairment: Rationale and design of the double-blind randomized controlled trial PD-CogT-Sleep
- Virus-specific effects of disease-modifying therapies on herpesvirus antibody titers in multiple sclerosis
- Disease-modifying therapies (DMTs) discontinuation in older relapsing-remitting multiple sclerosis (RRMS) patients with stable disease: Two-year randomized, controlled trial.
BibTeX
@misc{gomez2026sample,
title = {{Sample Size and Power Calculations Based on Endpoint Responsiveness: Applications to Trials of Disease-Modifying Therapies in Parkinson's Disease}},
author = {M. Pedrera Gomez and C. Bernasconi and C. Mazza and S. Belachew},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.26363876},
url = {https://www.medrxiv.org/content/10.64898/2026.09.29.26363876v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Sample Size and Power Calculations Based on Endpoint Responsiveness: Applications to Trials of Disease-Modifying Therapies in Parkinson's Disease
AU - M. Pedrera Gomez
AU - C. Bernasconi
AU - C. Mazza
AU - S. Belachew
PY - 2026
DA - 2026/09/29
PB - medRxiv
DO - 10.64898/2026.09.29.26363876
UR - https://www.medrxiv.org/content/10.64898/2026.09.29.26363876v1
AB - In Parkinsons disease (PD), early phase clinical trials of disease-modifying agents generally use the MDS-UPDRS Part III as the primary outcome measure of motor function, which typically requires a large sample and/or a long (12- 18 months) treatment duration, even if a substantial treatment effect is assumed. This is due to the rather slow rate of early PD progression relative to the variability of the MDS-UPDRS Part III assessments. Using placebo-arm data from four recent large Phase 2 trials of early-stage PD (SPARK, PASADENA, PADOVA and LUMA), the sample size needed to detect a range of assumed treatment effects on MDS-UPDRS Part III progression was estimated. The trial sample size estimates obtained for MDS-UPDRS Part III and for smartphone-based sensor-derived motor functional composite (MFC) endpoints were compared using an approach based on relative responsiveness to disease progression. The calculations were also implemented in an interactive, publicly accessible application. Powering a one-year trial using the MFC1 endpoint, derived from three active assessments (6-minute walk, U-turn and Hand Pronation-Supination), or the MFC2, which adds 60-Second Typing, was projected to reduce the required sample size by more than half relative to the MDS-UPDRS Part III, assuming equivalent proportional treatment effects.
ER -