title: Biological quality control for cardiopulmonary exercise testing in multicenter clinical trials.
abstract: BACKGROUND
  Precision and accuracy assurance in cardiopulmonary exercise testing (CPET) facilitates multicenter clinical trials by maximizing statistical power and minimizing participant risk. Current guidelines recommend quality control that is largely based on precision at individual testing centers (minimizing test-retest variability). The aim of this study was to establish a multicenter biological quality control (BioQC) method that considers both precision and accuracy in CPET.
  
  
  METHODS
  BioQC testing was 6-min treadmill walking at 20 W and 70 W (below the lactate threshold) with healthy non-smoking laboratory staff (15 centers; ~16 months). Measurements were made twice within the initial 4 weeks and quarterly thereafter. Quality control was based on: 1) within-center precision (coefficient of variation [CV] for oxygen uptake [V̇O2], carbon dioxide output [V̇CO2], and minute ventilation [V̇E] within ±10%); and 2) a criterion that V̇O2 at 20 W and 70 W, and ∆V̇O2/∆WR were each within ±10 % predicted. "Failed" BioQC tests (i.e., those outside the predetermined criterion) prompted troubleshooting and repeated measurements. An additional retrospective analysis, using a composite z-score combining both BioQC precision and accuracy of V̇O2 at 70 W and ∆V̇O2/∆WR, was compared with the other methods.
  
  
  RESULTS
  Of 129 tests (5 to 8 per center), 98 (76%) were accepted by within-center precision alone. Within-center CV was <9%, but between-center CV remained high (9.6 to 12.5%). Only 43 (33%) tests had all V̇O2 measurements within the ±10% predicted criterion. However, a composite z-score of 0.67 identified 67 (52%) non-normal outlying tests, exclusion of which coincided with the minimum CV for CPET variables.
  
  
  CONCLUSIONS
  Study-wide BioQC using a composite z-score can increase study-wide precision and accuracy, and optimize the design and conduct of multicenter clinical trials involving CPET.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01072396; February 19, 2010.
authors.affiliation: Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson Street, Building CDCRC, Torrance, CA, 90502, USA. porszasz@ucla.edu.
authors.forename: Janos
authors.initials: J
authors.lastname: Porszasz
authors.affiliation: TechEd Consultants, Inc., Mason, MI, USA. sblonshine@techedconsultants.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Blonshine
authors.affiliation: Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson Street, Building CDCRC, Torrance, CA, 90502, USA. rcao@labiomed.org.
authors.forename: Robert
authors.initials: R
authors.lastname: Cao
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. heather.paden@boehringer-ingelheim.com.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Paden
authors.affiliation: Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson Street, Building CDCRC, Torrance, CA, 90502, USA. casaburi@ucla.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.affiliation: Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson Street, Building CDCRC, Torrance, CA, 90502, USA. hrossiter@ucla.edu.|Faculty of Biological Sciences, University of Leeds, Leeds, UK. hrossiter@ucla.edu.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Rossiter
mesh_terms: D000328:Adult; D002245:Carbon Dioxide / Q000378:metabolism*; D002986:Clinical Trials as Topic; D005080:Exercise Test / Q000592:standards*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010101:Oxygen Consumption / Q000502:physiology*; D012123:Pulmonary Ventilation / Q000502:physiology*; D011786:Quality Control
chemical_list: D002245:Carbon Dioxide