title: A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.
abstract: OBJECTIVE
  To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases.
  
  
  METHODS
  Registry based study of ClinicalTrials.gov registration entries.
  
  
  METHODS
  The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate.
  
  
  METHODS
  Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison.
  
  
  RESULTS
  Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%).
  
  
  CONCLUSIONS
  Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.
authors.affiliation: Department of Biostatistics, University of Liverpool, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK. stubel168@msn.com.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Bell
authors.affiliation: Department of Biostatistics, University of Liverpool, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK. cat1@liverpool.ac.uk.
authors.forename: Catrin
authors.initials: C
authors.lastname: Tudur Smith
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D006801:Humans; D035583:Rare Diseases / Q000628:therapy*; D012042:Registries; D012107:Research Design