The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial.
OBJECTIVE
The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts.


METHODS
As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps+/-values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator).


RESULTS
For the reference tape, the cumulative ps+/-value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative rho=0.84; P<0.001).


CONCLUSIONS
Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.
Dittrich
Ralf
R
Department of Neurology, University Hospital of Münster, Germany.
Ritter
Martin A
MA
Kaps
Manfred
M
Siebler
Mario
M
Lees
Kennedy
K
Larrue
Vincent
V
Nabavi
Darius G
DG
Ringelstein
E Bernd
EB
Markus
Hugh S
HS
Droste
Dirk W
DW
D001241:Aspirin / Q000627:therapeutic use*; D016893:Carotid Stenosis / Q000150:complications*; D000077144:Clopidogrel; D006801:Humans; D020766:Intracranial Embolism / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000209:etiology; D015337:Multicenter Studies as Topic; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011786:Quality Control; D016032:Randomized Controlled Trials as Topic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017585:Ultrasonography, Doppler, Transcranial
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin