Analysis of Participant Withdrawal in Huntington Disease Clinical Trials
Article type: Research Article
Authors: Banno, Haruhikoa; b; 1 | Andrzejewski, Kelly L.c; d; 1 | McDermott, Michael P.e; f | Murphy, Alyssaa | Majumder, Madhurimae | de Blieck, Elisabeth A.f | Auinger, Peggyf | Cudkowicz, Merit E.a | Atassi, Nazema; *
Affiliations: [a] Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Nagoya University Graduate School of Medicine, Nagoya, Japan | [c] Department of Neurology, University of Rochester, Rochester, NY, USA | [d] Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA | [e] Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA | [f] Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester, Rochester, NY, USA
Correspondence: [*] Correspondence to: Nazem Atassi, MD, MMSc, Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge Street, Suite 656, Boston, MA 02114, USA. Tel.: +1 617 643 6114; Fax: +1 617 724 7290; E-mail: [email protected].
Note: [1] These authors are equally contributed.
Abstract: Background: Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials. Objective: We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal. Methods: Analyses of participant withdrawal were performed for three randomized, double-blind, placebo-controlled trials including the CARE-HD (coenzyme Q10 and remacemide in HD, n = 347), DOMINO (pilot study of minocycline in HD, n = 114), and 2CARE (coenzyme Q10 in HD, n = 609) trials. Reasons for withdrawal were obtained by review of textual data in the study databases. Participant demographic and clinical characteristics were analyzed as potential predictors of time to withdrawal using Cox-proportional hazards models. Results: Estimated probabilities of withdrawal at 12 months were 2.9% for CARE-HD, 10.5% for DOMINO, and 5.9% for 2CARE. The top reasons for withdrawal (202 in total), expressed as mean percentage across the three trials, were loss to follow-up (23.2%), death (15.9%), and loss of interest/desire to participate (15.2%). Baseline and time-dependent variables associated with time to withdrawal were mainly motor, behavioral, and functional scores. Age, gender, ethnicity, and educational level were not associated with time to withdrawal in any of the three studies. Conclusions: The estimated withdrawal probability at 12 months ranged from 2.9% to 10.5% in the three HD trials considered here. A possible strategy to improve retention of participants in future HD clinical trials is to enroll individuals with higher baseline functional and behavioral status.
Keywords: Huntington disease, clinical trial, patient selection, retention
DOI: 10.3233/JHD-170246
Journal: Journal of Huntington's Disease, vol. 6, no. 2, pp. 149-156, 2017
