Botulinum neurotoxins for the treatment of focal dystonias: Review of rating tools used in clinical trials

Abstract

Botulinum neurotoxins (BoNTs) are used to achieve therapeutic benefit in focal dystonia. An expert panel recently reviewed published evidence on the efficacy of BoNTs for the treatment of focal dystonias and produced recommendations for clinical practice. Another panel reviewed the clinimetric properties of rating scales for dystonia and produced recommendations for current usage and future directions. Considering that the strength of evidence derives not only from the quality of the study design, but also from usage of validated outcome measures, we combined the information provided by these two recent reviews and assessed the appropriateness of the rating instruments used in clinical trials on BoNT treatment in focal dystonia.Data sources included all the publications on BoNT treatment for focal dystonias reviewed by the recent evidence-based analysis. We reviewed all rating instruments used to assess primary and secondary outcome following BoNT treatment. The publications were allocated into five topics according to the focal dystonia type reviewed in the meta-analysis: blepharospasm, oromandibular dystonia, cervical dystonia, upper limb dystonia, and laryngeal dystonia. For each topic, papers were divided, according to the terminology used in the meta-analysis, into placebo-controlled, active comparator and methodological or uncontrolled. For each topic we identified the rating tools used in each study class and annotated which were the mostly used in each focal dystonia type. Outcome measures included tools related to motor and non-motor features, such as pain and depression, and functional as well as health-related quality of life features. Patient- and investigator-reported outcomes were also included. Rating instruments were classified as recommended, suggested, listed or not included, based on recommendations produced by the rating scale task force. Both primary and secondary outcome measures were assessed. As a final step we compared current practice, as summarized by the meta-analysis, with the recommendations of the rating scales panel.For blepharospasm, three placebo-controlled trials used suggested scales, one active-comparator study used a recommended scale and three active-comparator studies used suggested scales. For oromandibular dystonia, one placebo-controlled study used a suggested scale. For cervical dystonia, six placebo-controlled trials used a recommended scale, four active-comparator trials used a recommended scale and one active-comparator study used a suggested scale. For upper limb and laryngeal dystonia, no trial used validated instruments.Appropriately designed studies should be based on recommended rating instruments. Therapeutic trials not using clinimetrically tested rating measures do not provide sufficient information on efficacy of BoNT treatment, even if the study design is robust. Further research is needed to develop and validate new tools to assess all types of focal dystonia and to apply them in prospective placebo-controlled clinical trials.