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Placebo response in degenerative cerebellar ataxias: a descriptive review of randomized, placebo-controlled trials

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Abstract

Placebo response in degenerative cerebellar ataxias (CAs) has never been studied despite the large number of randomized controlled trials (RCTs) that have been conducted. In this descriptive review, we aimed to examine the placebo response in patients with CAs. We performed a literature search on PubMed for RCTs on CAs that were published from 1977 to January 2020 and collected data on the changes from the baseline to the endpoint on various objective ataxia-associated clinical rating scales. We reviewed 56 clinical trials, finally including 35 parallel-group studies and excluding 21 cross-over studies. The included studies were categorized as follows: (1) studies showing significant improvements in one or more ataxia scales in the placebo groups (n = 3); (2) studies reporting individual placebo responders with improvements in one or more ataxia scales in the placebo groups (n = 5)—the overall proportion of placebo responders was 31.9%; (3) studies showing mean changes in the direction of improvement in at least one ataxia scale in the placebo groups, though not statistically significant (n = 19); (4) studies showing no placebo response in any of the ataxia scales in the placebo groups (n = 4); (5) studies where data on the placebo groups were unavailable (n = 9). This review demonstrated the placebo response in patients with CAs on various objective ataxia scales. Our study emphasizes that the placebo response should be considered when designing, analyzing, and interpreting clinical trials and in clinical practice in CA patients.

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Data access and responsibility statement

HJ. Kim and JH. Choi had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Department of Neurology and Movement Disorder Center, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea

    Ji-Hyun Choi, Han-Joon Kim & Beomseok Jeon

  2. Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea

    Ji-Hyun Choi

  3. Department of Neurology, Chungnam National University Sejong Hospital, Sejong-si, South Korea

    Chaewon Shin

  4. Department of Neurology, Chungnam National University College of Medicine, Daejeon, South Korea

    Chaewon Shin

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  1. Ji-Hyun Choi
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Conception: CS and HJK, execution: JHC, CS, HJK, and BJ, Writing of the first draft: JHC and HJK, review and critique: JHC, CS, HJK, and BJ.

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Correspondence to Han-Joon Kim.

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Choi, JH., Shin, C., Kim, HJ. et al. Placebo response in degenerative cerebellar ataxias: a descriptive review of randomized, placebo-controlled trials. J Neurol 269, 62–71 (2022). https://doi.org/10.1007/s00415-020-10306-7

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