title: The methods for handling missing data in clinical trials influence sample size requirements.
abstract: OBJECTIVE
  Results of studies estimating osteoarthritis progression may be affected by missing values. In clinical trials assessing disease-modifying osteoarthritis drugs, sample sizes should be calculated using close estimates of outcome variables.
  
  
  METHODS
  Supposing a two-parallel group design in hip osteoarthritis clinical trials, we estimated sample sizes using the joint space width (JSW), number of patients with JSW progression >0.5 mm (JSN), time to total hip arthroplasty (THA), and time to JSN or THA using several approaches to deal with missing data.
  
  
  RESULTS
  Three-year clinical trials testing a treatment effect of 50%, with a power of 80%, could require sample sizes of 121 patients for JSW, 57 for JS progression using multiple imputation for handling missing values; 200 for THA; and 47 for JSN or THA. These numbers vary greatly depending on the approach chosen for handling missing data.
  
  
  CONCLUSIONS
  These results can help investigators plan clinical trials to select the primary outcome and a priori specify the way missing data will be handled.
authors.affiliation: Université Paris V-René Descartes, Faculté de Médecine Cochin Port-Royal and Clinique de Rhumatologie, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Guy-Robert
authors.initials: GR
authors.lastname: Auleley
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Gabriel
authors.initials: G
authors.lastname: Baron
authors.forename: Jean-Francis
authors.initials: JF
authors.lastname: Maillefert
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D015207:Osteoarthritis, Hip / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents