Angiographic core laboratory reproducibility analyses: implications for planning clinical trials using coronary angiography and left ventriculography end-points.
OBJECTIVE
To assess reproducibility of core laboratory performance and impact on sample size calculations.


BACKGROUND
Little information exists about overall reproducibility of core laboratories in contradistinction to performance of individual technicians. Also, qualitative parameters are being adjudicated increasingly as either primary or secondary end-points. The comparative impact of using diverse indexes on sample sizes has not been previously reported.


METHODS
We compared initial and repeat assessments of five quantitative parameters [e.g., minimum lumen diameter (MLD), ejection fraction (EF), etc.] and six qualitative parameters [e.g., TIMI myocardial perfusion grade (TMPG) or thrombus grade (TTG), etc.], as performed by differing technicians and separated by a year or more. Sample sizes were calculated from these results. TMPG and TTG were also adjudicated by a second core laboratory.


RESULTS
MLD and EF were the most reproducible, yielding the smallest sample size calculations, whereas percent diameter stenosis and centerline wall motion require substantially larger trials. Of the qualitative parameters, all except TIMI flow grade gave reproducibility characteristics yielding sample sizes of many 100's of patients. Reproducibility of TMPG and TTG was only moderately good both within and between core laboratories, underscoring an intrinsic difficulty in assessing these.


CONCLUSIONS
Core laboratories can be shown to provide reproducibility performance that is comparable to performance commonly ascribed to individual technicians. The differences in reproducibility yield huge differences in sample size when comparing quantitative and qualitative parameters. TMPG and TTG are intrinsically difficult to assess and conclusions based on these parameters should arise only from very large trials.
Steigen
Terje K
TK
Cardiovascular Imaging Research Core Laboratory, Division of Cardiology, Vancouver Hospital, 3300-950 W. 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
Claudio
Cheryl
C
Abbott
David
D
Schulzer
Michael
M
Burton
Jeff
J
Tymchak
Wayne
W
Buller
Christopher E
CE
John Mancini
G B
GB
D002986:Clinical Trials as Topic / Q000592:standards*; D017023:Coronary Angiography / Q000592:standards*; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000000981:diagnostic imaging; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging; D006331:Heart Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007753:Laboratories / Q000592:standards*; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging; D015588:Observer Variation; D015397:Program Evaluation; D011785:Quality Assurance, Health Care; D015635:Radionuclide Ventriculography / Q000592:standards*; D015203:Reproducibility of Results; D018401:Sample Size; D012720:Severity of Illness Index; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left