title: Impact of repeated measures of joint space width on the sample size calculation: An application to hip osteoarthritis.
abstract: OBJECTIVE
  The aims of the study were to investigate the impact of aggregation of repeated readings (a) on minimising variability of joint space width (JSW) measurements based on calculation of the smallest detectable difference (SDD) and (b) on sample size calculation in a hip OA randomized controlled trial (RCT).
  
  
  METHODS
  (a) Post-hoc analysis of 50 radiographs from a hip OA RCT (ECHODIAH). JSW reliability was calculated by the SDD through the aggregation of repeated readings of hip OA radiographs by an experienced rheumatologist. (b) The observed SDDs were applied to the real ECHODIAH data, to determine the post-hoc theoretical sample sizes.
  
  
  RESULTS
  (a) Although the intra-reader reliability did not improve, SDDs decreased from 0.75 mm to 0.27 mm when aggregating two or more consecutive readings. (b) A significant decrease of sample size was noticed until three consecutive paired JSW measurements, with a sample size ranging from 6588 patients per group (SDD=0.75 mm) to 377 patients (SDD=0.45 mm). However, an increase of the sample size was observed for smaller SDDs.
  
  
  CONCLUSIONS
  In hip OA, the aggregation of repeated radiograph readings leads to a significant decrease in SDD, although the intra-reader reliability of the experienced reader remains stable. The decrease in SDD allowed to reduce significantly the post-hoc calculation of sample size until a SDD value of 0.45 mm. For smaller cut-offs of radiological progression, the sample size increased again indicating that gain in sensitivity does not automatically lead to gain in sample size, particularly if the treatment effect is limited.
authors.affiliation: Rheumatology department, Medicine Faculty, Dijon University Hospital, 21000 Dijon, France; Inserm U1093, Burgundy University, 21000 Dijon, France; Paris-Descartes University, Medicine Faculty, UPRES-EA 4058, Cochin Hospital, Rheumatology B Department, 75014 Paris, France. Electronic address: paul.ornetti@chu-dijon.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Ornetti
authors.affiliation: CIC-P Inserm 1432, Plateforme d'Investigation Technologique, Dijon University Hospital, Dijon, France; Rheumatology department, Pitié-Salpétrière Hospital, AP-HP, 75013 Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
authors.affiliation: CIC-P Inserm 1432, Plateforme d'Investigation Technologique, Dijon University Hospital, 21000 Dijon, France.
authors.forename: Davy
authors.initials: D
authors.lastname: Laroche
authors.affiliation: Division of clinical epidemiology, Geneva University Hospital and University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.affiliation: Paris-Descartes University, Medicine Faculty, UPRES-EA 4058, Cochin Hospital, Rheumatology B Department, 75014 Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Rheumatology department, Medicine Faculty, Dijon University Hospital, 21000 Dijon, France; Inserm U1093, Burgundy University, 21000 Dijon, France.
authors.forename: Jean-Francis
authors.initials: JF
authors.lastname: Maillefert
mesh_terms: D000368:Aged; D001837:Body Weights and Measures; D018450:Disease Progression; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging*; D010865:Pilot Projects; D011859:Radiography; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size
keywords: Hip; Joint space; Osteoarthritis; Randomized clinical trial; Sample size; Smallest detectable difference