title: Biologically implausible carotid intima-media thickness measurement values: effects on rate of change over time.
abstract: OBJECTIVE
  Carotid intima-media thickness (CIMT) is a marker of atherosclerosis that is commonly used to assess the effect of therapeutic interventions. It is currently unclear to what extent biologically implausible values affect treatment effects. We evaluated the impact of biologically implausible CIMT values on the estimated rate of change in CIMT.
  
  
  METHODS
  Data were used from the METEOR (Measuring Effects on Intima-media Thickness: an Evaluation of Rosuvastatin) trial. METEOR was a randomized, placebo-controlled trial showing that rosuvastatin reduced the 2-year change in CIMT among low-risk individuals with subclinical atherosclerosis. In the main METEOR analysis, the data were analyzed without exclusion of biologically implausible data. In this post-hoc analysis, we constructed twelve definitions to define mildly or extremely biologically implausible values using distance from the interquartile range, median or mean. We evaluated the effect of removing implausible values on the estimated rate of change in CIMT.
  
  
  RESULTS
  The percentage of biologically implausible CIMT values ranged from 0.6% to 9.7%, depending on the definition used. Across all definitions, removal of biologically implausible CIMT values marginally reduced standard errors and did not change the primary outcome (i.e., a nonsignificant change in the rosuvastatin group, significant progression in the placebo group, and a statistically significant difference between treatment groups).
  
  
  CONCLUSIONS
  This study was focussed on the impact of implausible values in the analytical part of a CIMT study. Ultrasound images were not re-examined to determine whether an implausible measurement was due to measurement error or temporal morphological thickening,
  
  
  CONCLUSIONS
  Removal of biologically implausible CIMT values marginally decreased the variability of the estimated rate of change in CIMT without having a large impact on the estimated rate of change.
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands. s.a.e.peters@umcutrecht.nl
authors.forename: Sanne A E
authors.initials: SA
authors.lastname: Peters
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.forename: Mike K
authors.initials: MK
authors.lastname: Palmer
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: John R
authors.initials: JR
authors.lastname: Crouse
authors.forename: Daniel H
authors.initials: DH
authors.lastname: O'Leary
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Evans
authors.forename: Joel S
authors.initials: JS
authors.lastname: Raichlen
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D059168:Carotid Intima-Media Thickness / Q000592:standards; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011237:Predictive Value of Tests; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium