title: Sample size and cost analysis for pulmonary arterial hypertension drug trials using various imaging modalities to assess right ventricular size and function end points.
abstract: BACKGROUND
  Placebo-controlled trials for pulmonary arterial hypertension are no longer acceptable because new therapies must show clinically significant effects on top of standard treatment. The purpose of this study was to estimate sample sizes and imaging costs for the planning of a hypothetical pulmonary arterial hypertension drug trial using imaging to detect changes in right ventricular size and function in response to combined therapy.
  
  
  RESULTS
  Same-day cardiovascular MR (CMR) and 2-dimensional (2D) and 3D transthoracic echocardiography (2DTTE and 3DTTE) were performed in 22 patients with pulmonary arterial hypertension (54±13 years of age) twice, 6 months apart. Short-axis CMR cines and full-volume 3DTTE data sets of the right ventricle were used to measure end-diastolic volume and ejection fraction. Fractional area change was obtained from 2DTTE. Sample size calculations used a 2-sample t test model incorporating differences between baseline and 6-month measurements. Cost estimates were made using the Medicare fee schedule. No significant differences were noted between baseline and follow-up measurements. Large SDs reflected variable progression of disease in individual patients on standard therapy and measurement variability. These sources of variability resulted in intertechnique differences in sample sizes: to detect a change of 5% to 15% in 3DTTE-derived right ventricular ejection fraction and fractional area change or change of 15 to 30 mL in 3DTTE right ventricular end-diastolic volume; sample sizes were 2× to 2.5× those required by CMR. As a result, the total cost of a trial using complete TTE was greater than CMR, which was greater than limited TTE.
  
  
  CONCLUSIONS
  Because of lower measurement variability, CMR is more cost saving in pulmonary arterial hypertension drug trials than echocardiography, unless limited TTE is used.
authors.affiliation: Section of Cardiology, Department of Medicine, and Department of Radiology, University of Chicago, IL.
authors.forename: Karima
authors.initials: K
authors.lastname: Addetia
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Bhave
authors.forename: Corey E
authors.initials: CE
authors.lastname: Tabit
authors.forename: Mardi
authors.initials: M
authors.lastname: Gomberg-Maitland
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Freed
authors.forename: Karin E
authors.initials: KE
authors.lastname: Dill
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
authors.forename: Victor
authors.initials: V
authors.lastname: Mor-Avi
authors.forename: Amit R
authors.initials: AR
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic / Q000191:economics*; D017046:Cost Savings; D003362:Cost-Benefit Analysis; D003952:Diagnostic Imaging / Q000191:economics*; D004359:Drug Therapy, Combination; D019560:Echocardiography, Three-Dimensional / Q000191:economics; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D017048:Health Care Costs; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics* / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine / Q000191:economics; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D011237:Predictive Value of Tests; D018401:Sample Size; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents
keywords: cardiac imaging techniques; hypertension, pulmonary; right ventricle; sample size