, Volume 11, Issue 1, pp 117–127 | Cite as

Designing Clinical Trials for Dystonia

  • Wendy R. Galpern
  • Christopher S. Coffey
  • Alberto Albanese
  • Ken Cheung
  • Cynthia L. Comella
  • Dixie J. Ecklund
  • Stanley Fahn
  • Joseph Jankovic
  • Karl Kieburtz
  • Anthony E. Lang
  • Michael P. McDermott
  • Jeremy M. Shefner
  • Jan K. Teller
  • John L. P. Thompson
  • Sharon D. Yeatts
  • H. A. Jinnah


With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.


Dystonia Clinical trials Exploratory trials Confirmatory trials Adaptive designs 



This article was based, in part, on a workshop that was held in May 2012 involving an international group of dystonia clinicians, clinical trialists, and statisticians, as well as representatives from industry and the US Food and Drug Administration. The workshop was sponsored by the Dystonia Medical Research Foundation, The Dystonia Coalition (U54 NS65701 from NINDS and the Office of Rare Diseases Research in NCATS at NIH), and the National Institute of Neurological Disorders and Stroke (U13NS079084). Full conflict of interest disclosures are available in the electronic supplementary material for this article.

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. (outside the U.S.) 2013

Authors and Affiliations

  • Wendy R. Galpern
    • 1
  • Christopher S. Coffey
    • 2
  • Alberto Albanese
    • 3
  • Ken Cheung
    • 4
  • Cynthia L. Comella
    • 5
  • Dixie J. Ecklund
    • 2
  • Stanley Fahn
    • 6
  • Joseph Jankovic
    • 7
  • Karl Kieburtz
    • 8
  • Anthony E. Lang
    • 9
  • Michael P. McDermott
    • 10
  • Jeremy M. Shefner
    • 11
  • Jan K. Teller
    • 12
  • John L. P. Thompson
    • 4
  • Sharon D. Yeatts
    • 13
  • H. A. Jinnah
    • 14
  1. 1.National Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA
  2. 2.Clinical Trials Statistical & Data Management CenterUniversity of IowaIowa CityUSA
  3. 3.Department of NeurologyCatholic University and Carlo Besta National Neurological InstituteMilanItaly
  4. 4.Department of BiostatisticsColumbia UniversityNew YorkUSA
  5. 5.Rush University Medical CenterChicagoUSA
  6. 6.Movement Disorder Division, Neurological InstituteColumbia UniversityNew YorkUSA
  7. 7.Parkinson’s Disease Center and Movement Disorders Clinic, Department of NeurologyBaylor College of MedicineHoustonUSA
  8. 8.Center for Human Experimental TherapeuticsUniversity of Rochester Medical CenterRochesterUSA
  9. 9.Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s DiseaseToronto Western HospitalTorontoCanada
  10. 10.Department of Biostatistics and Computational Biology and Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  11. 11.Department of NeurologyUpstate Medical UniversitySyracuseUSA
  12. 12.Dystonia Medical Research FoundationChicagoUSA
  13. 13.Department of Public Health SciencesMedical University of South CarolinaCharlestonUSA
  14. 14.Department of Neurology, Human Genetics & PediatricsEmory UniversityAtlantaUSA

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