Statistical Considerations in the Design of Clinical Trials Targeting Prodromal Parkinson Disease.

Autor:	Macklin EA; From the Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Biostatistics (C.S.C., M.C.B.), College of Public Health, University of Iowa, Iowa City; and Institute for Neurodegenerative Disorders (J.P.S.), New Haven, CT. emacklin@mgh.harvard.edu., Coffey CS; From the Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Biostatistics (C.S.C., M.C.B.), College of Public Health, University of Iowa, Iowa City; and Institute for Neurodegenerative Disorders (J.P.S.), New Haven, CT., Brumm MC; From the Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Biostatistics (C.S.C., M.C.B.), College of Public Health, University of Iowa, Iowa City; and Institute for Neurodegenerative Disorders (J.P.S.), New Haven, CT., Seibyl JP; From the Biostatistics Center (E.A.M.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Biostatistics (C.S.C., M.C.B.), College of Public Health, University of Iowa, Iowa City; and Institute for Neurodegenerative Disorders (J.P.S.), New Haven, CT.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2022 Aug 16; Vol. 99 (7 Suppl 1), pp. 68-75.
DOI:	10.1212/WNL.0000000000200897
Abstrakt:	Clinical trials testing interventions for prodromal Parkinson disease (PD) hold particular promise for preserving neuronal function and thereby slowing or even forestalling progression to overt PD. Selection of the appropriate target population and outcome measures presents challenges unique to prodromal PD. We propose 3 clinical trial designs, spanning phase 2a, phase 2b, and phase 3 development, that might serve as templates for prodromal PD trials. The proposed phase 2a trial is of a 3-arm design of short duration and focuses on proof of concept with respect to target engagement and change in a motor outcome in a subset of prodromal participants who already manifest asymptomatic but measurable motor dysfunction as an exploratory aim. The proposed phase 2b trial suggests progression of dopamine transporter imaging specific binding ratio as a primary outcome evaluated annually over 2 years with phenoconversion to PD as a key secondary outcome. The proposed phase 3 trial is a large, simple design of a nutraceutical or behavioral intervention with remote administration and phenoconversion as the primary outcome. We then consider what additional data are needed in the short term to better design prodromal PD trials and examine what longer-term goals would accelerate discovery of safe and effective therapies for individuals at risk of PD. Clear and potentially context-specific definitions of phenoconversion and validation of intermediate endpoints are needed in the short term. The use of adaptive trial designs, master protocols, and research registries would help accelerate therapy development in the long term. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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