Biological quality control for cardiopulmonary exercise testing in multicenter clinical trials

Porszasz, Janos; Blonshine, Susan; Cao,  Robert; Paden, Heather; Casaburi, Richard; Rossiter, Harry. BMC

Pulmonary Medicine, December 2016, Vol. 16 Issue: Number 1 p1-10, 10p;

Abstract: 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.   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 V̇O2at 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 V̇O2at 70 W and ∆V̇O2/∆WR, was compared with the other
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 V̇O2measurements 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.
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.