title: Feasibility of placebo-controlled trial designs for new CFTR modulator evaluation.
abstract: BACKGROUND
  New CFTR modulators are in development that sponsors anticipate will be comparable or superior to approved modulators. Testing these agents for efficacy will require either placebo-controlled or active-comparator trials.
  
  
  METHODS
  We surveyed US CF physicians and their patients eligible to receive approved modulators or their families for willingness to participate in placebo-controlled modulator trials of varying duration.
  
  
  RESULTS
  Interest in placebo-controlled trials of short duration (2-4weeks) was greatest, with few respondents, particularly among patient respondents, willing to consider 6month studies. Patients/families with access to approved modulators were consistently less interested in placebo-controlled modulator trials of any duration.
  
  
  CONCLUSIONS
  Sample size and interpretability advantages of placebo-controlled trials outweigh alternative active-comparator trials, but must consider physician and patient thresholds for forgoing treatment with approved modulators. Enrollment will be most feasible for short-duration trials and those conducted among populations without access to approved modulators.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, USA. Electronic address: drv15@case.edu.
authors.forename: Donald R
authors.initials: DR
authors.lastname: VanDevanter
authors.affiliation: University of Washington and Seattle Children's Hospital, Seattle, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Cystic Fibrosis Foundation, Bethesda, USA; John Hopkins School of Medicine, Baltimore, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyle
mesh_terms: D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000235:genetics / Q000523:psychology / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005240:Feasibility Studies; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D010358:Patient Participation; D018579:Patient Selection; D045808:Refusal to Participate / Q000523:psychology*; D018401:Sample Size; D035703:Therapies, Investigational / Q000379:methods / Q000523:psychology; D013997:Time Factors
chemical_list: D049990:Membrane Transport Modulators; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Enrollment; Modulator; Placebo; Trial design