title: A maximum confidence approach for measuring progression and regression of coronary artery disease in clinical trials.
abstract: BACKGROUND
  Imaging trials using arteriography have been shown to be effective alternatives to clinical end point studies of atherosclerotic vascular disease progression and the effect of therapy on it. However, lack of consensus on what end point measures constitute meaningful change presents a problem for quantitative coronary arteriographic (QCA) approaches. Furthermore, standardized approaches to QCA studies have yet to be established. To address these issues, two different arteriographic approaches were compared in a clinical trial, and the degree of concordance between disease change measured by these two approaches and clinical outcomes was assessed.
  
  
  RESULTS
  In the Familial Atherosclerosis Treatment Study (FATS) of three different lipid-lowering strategies in 120 patients, disease progression/regression was assessed by two arteriographic approaches: QCA and a semiquantitative visual approach (SQ-VIS). Lesions classified with SQ-VIS as "not," "possibly," or "definitely" changed were measured by QCA to change by 10% stenosis in 0.3%, 11%, and 81% of cases, respectively. The "best" measured value for distinguishing definite from no change was identified as 9.3% stenosis by logistic regression analysis. The primary outcome analysis of the FATS trial, using a continuous variable estimate of percent stenosis change, gave almost the same favorable result whether by QCA or SQ-VIS.
  
  
  CONCLUSIONS
  The excellent agreement between these two fundamentally different methods of disease change assessment and the concordance between disease change and clinical outcomes greatly strengthens confidence both in these measurement techniques and in the overall findings of the study. These observations have important implications for the design of clinical trials with arteriographic end points.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle 98195.
authors.forename: B G
authors.initials: BG
authors.lastname: Brown
authors.forename: L A
authors.initials: LA
authors.lastname: Hillger
authors.forename: C
authors.initials: C
authors.lastname: Lewis
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhao
authors.forename: D
authors.initials: D
authors.lastname: Sacco
authors.forename: B
authors.initials: B
authors.lastname: Bisson
authors.forename: L
authors.initials: L
authors.lastname: Fisher
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D017023:Coronary Angiography / Q000379:methods*; D003327:Coronary Disease / Q000000981:diagnostic imaging*; D005069:Evaluation Studies as Topic; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D015203:Reproducibility of Results