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The most appropriate primary outcomes to design clinical trials on H untington's disease: meta‐analyses of cohort studies and randomized placebo‐controlled trials
Author(s) -
Salem Linda,
Saleh Nadine,
Youssov Katia,
Olivier Audrey,
Charles Perrine,
Scherer Clarisse,
Verny Christophe,
BachoudLévi AnneCatherine,
Maison Patrick
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12077
Subject(s) - randomized controlled trial , medicine , placebo , verbal fluency test , completely randomized design , cohort , physical therapy , clinical trial , cognition , neuropsychology , psychiatry , biology , pathology , alternative medicine , horticulture
Huntington's disease ( HD ) is a rare multifactorial neurodegenerative disease. Both its natural course and any placebo effect are poorly known. All are obstacles to design randomized controlled trials ( RCT s). We conducted meta‐analyses of RCT s and cohorts on all parameters of the U nified H untington's D isease R ating S cale to determine the most appropriate outcomes and to minimize the number of patients required to design RCT s in HD . Twenty‐four RCT s were included, involving 838 patients with a mean age of 50.0 ± 2.3 years and a mean total functional capacity ( TFC ) score of 9.8 ± 0.6. Nineteen cohorts were included involving 1939 patients with a mean age of 48.9 ± 2.3 years and a mean TFC of 10.1 ± 0.7. Significant deterioration was observed in RCT s for all scores except behavioral score. Effect sizes were comparable between RCT s and cohorts for each test except that there was a significant difference for TFC . The weighted mean deterioration per year on the TFC scale was −0.5 (0.2) in RCT s and −0.8 (0.2) in cohorts. The lowest number of patients required per group in a RCT was for TFC (19 per group), whereas 30 patients would be required per group for the total motor score ( TMS ). For cognition, the verbal fluency test required the smallest number of patients: 104 per group. In conclusion, TMS and TFC are the most appropriate outcomes to design RCT s on HD likewise the verbal fluency test for cognition. Our results suggest an effect of placebo administration on the total functional capacity.