Haruhiko Banno1,2, Kelly L Andrzejewski3,4, Michael P McDermott5,6, Alyssa Murphy1, Madhurima Majumder5, Elisabeth A de Blieck6, Peggy Auinger6, Merit E Cudkowicz1, Nazem Atassi1. 1. Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Nagoya University Graduate School of Medicine, Nagoya, Japan. 3. Department of Neurology, University of Rochester, Rochester, NY, USA. 4. Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. 5. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA. 6. Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester, Rochester, NY, USA.
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.
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.
Authors: Eric A Fertuck; John Keilp; Inkyung Song; Melissa C Morris; Scott T Wilson; Beth S Brodsky; Barbara Stanley Journal: Psychother Psychosom Date: 2011-11-22 Impact factor: 17.659
Authors: J P Vonsattel; R H Myers; T J Stevens; R J Ferrante; E D Bird; E P Richardson Journal: J Neuropathol Exp Neurol Date: 1985-11 Impact factor: 3.685
Authors: Andrew McGarry; Michael McDermott; Karl Kieburtz; Elisabeth A de Blieck; Flint Beal; Karen Marder; Christopher Ross; Ira Shoulson; Peter Gilbert; William M Mallonee; Mark Guttman; Joanne Wojcieszek; Rajeev Kumar; Mark S LeDoux; Mary Jenkins; H Diana Rosas; Martha Nance; Kevin Biglan; Peter Como; Richard M Dubinsky; Kathleen M Shannon; Padraig O'Suilleabhain; Kelvin Chou; Francis Walker; Wayne Martin; Vicki L Wheelock; Elizabeth McCusker; Joseph Jankovic; Carlos Singer; Juan Sanchez-Ramos; Burton Scott; Oksana Suchowersky; Stewart A Factor; Donald S Higgins; Eric Molho; Fredy Revilla; John N Caviness; Joseph H Friedman; Joel S Perlmutter; Andrew Feigin; Karen Anderson; Ramon Rodriguez; Nikolaus R McFarland; Russell L Margolis; Eric S Farbman; Lynn A Raymond; Valerie Suski; Sandra Kostyk; Amy Colcher; Lauren Seeberger; Eric Epping; Sherali Esmail; Nancy Diaz; Wai Lun Alan Fung; Alan Diamond; Samuel Frank; Philip Hanna; Neal Hermanowicz; Leon S Dure; Merit Cudkowicz Journal: Neurology Date: 2016-12-02 Impact factor: 9.910