i-stat ctni Performance Verification vs. ABBOTT AxSYM

Transcription

1 Report #1 i-stat ctni Performance Verification vs. ABBOTT AxSYM i-stat Corporation - 1

2 Summary of Evaluation Study Results Correlation Slope Note 1 with comparative assay for [ctni]<25.0 ng/ml 0.13 Critical Decision Levels (Cut-offs): Current hospital [ctni] cutoffs for myocardial infarction: Cut-off at hospital, using the Abbott AxSYM Equivalent cut-off on the i-stat System 2.0 ng/ml 0.3 ng/ml Concordance Note 2 with comparative assay Abbott AxSYM 94% at current hospital cut-off and equivalent i-stat cut-off Imprecision Note3 in control fluids observed at hospital 5.4% Note 1-3 Please see Notes 1 through 3, on pages 4 and 5. The reader is encouraged to review the attached documentation carefully as it contains important information concerning the interpretation, relevance, and use of the results summarized above. i-stat Corporation - 2 -

3 Method Comparison Data Correlation results for [ctni] <25.0 ng/ml (based on the AxSYM values) are plotted below. Regression statistics are summarised in the following table. Corresponding data for the entire data set are summarised on the following page. Discordant points (open circles) were not included in calculation of slopes so as not to distort the inherent correlation representing the bulk of samples. Discordant points may be due to samples that were obtained >48 hours after patient presentation and that contained degradation products 1 and/or differences in antibody specificity between the two assays. Only the first replicates for each data pair were used in the plots and calculations i-stat vs Abbott AxSYM All results [ctni] < 25.0 ng/ml i-stat ctn AxSYM ctni n Least squares Slope Intercept r i-stat Corporation - 3 -

4 35 i-stat vs Abbott AxSYM All results i-stat ctni AxSYM ctni n Least squares Slope Intercept r i-stat Corporation - 4 -

5 Interpretation and Relevance of Reported Statistics 1. Correlation slopes for troponin assays from different manufacturers are rarely unity; this stems from the lack of a gold standard reference material and consequent differences in calibration from one manufacturer to another. Consequently, differences in result do not imply that one assay is correct and another errant. (Note: See the listed references 2,3 for typical inter-assay correlations.) The correlation slope reported here is that calculated for [ctni] < 25.0 ng/ml; this range was chosen so as to provide the best estimate of the slope in the range where critical decision levels are established by clinicians. Each clinical environment should confirm the reference range and the suitable critical decision levels in their specific setting. 5,6 Where the user wishes to establish i-stat ctni concentrations equivalent to existing comparative assay decision levels, these may be estimated by multiplying the latter by the correlation slope: [i-stat ctni] = Slope * [Comparative Assay ctni] 2. Concordance is defined as the frequency with which two assays agree in answering the question: Is the analyte concentration above or below a specific decision level? for a specific set of data (generally comprised of a specimen population typical of ED presentations with chest pain). Typical values of concordance in commercial ctni assays are 91 to 95%. 2,3 The concordance reported here was calculated from the method comparison data acquired during this study utilizing the current hospital cut-off for [ctni] abnormality and the equivalent cut-off value for the i-stat System. [See Critical Decision Levels (Cut-offs) on page 1 and the 2 2 Contingency Table below.] 2 2 Contingency Table (Concordance Table) Comparative Assay (Cut-off = 2.0 ng/ml) Positive Negative i-stat ctni (Equiv. Cut-off = 0.3 ng/ml) Positive 19 3 Negative 0 30 Concordance (%) = [19] + [30] 100 = 94% [19] + [3] + [0] + [30] i-stat Corporation - 5 -

6 3. Low-End Imprecision was established for the i-stat ctni test cartridge via in-house experiments. The plot of [ctni] vs. %CV was included in the 510(k) submission (see plot below). Each of 12 low level spiked samples (ITC, HyTest TM, Finland) were prepared and assayed by running simultaneously with three lots of i-stat ctni test cartridges on 18 i-stat 1 handheld analyzers. Whole blood employed in the experiment was drawn from 4 healthy donors. The imprecision (%CV) as a function of ctni concentration is illustrated in the following figure. i-stat Method Imprecision vs ctni Level %CV [ctni] (ng/ml) The efficient execution of site evaluation studies necessitates the stockpiling of patient samples as frozen plasmas for method correlation. Samples comprised of freeze-thawed plasmas are subject to artifactual changes that may affect absolute results 4 and precision in various ctni assays. Imprecision estimated from measurements in these sample types is therefore not expected to be representative of imprecision observed in the intended sample type, i.e. freshly drawn whole blood as used in the plot above. If on-site measurement of whole blood imprecision is desired, a whole blood protocol similar to the one used in the 510(k) analytical studies will be required. i-stat Corporation - 6 -

7 Reliable estimates of the i-stat ctni assay imprecision may be had in the following sources: Control fluids at hospital (i-stat) 5.4% Control fluids, factory lot calibration (i-stat) a 6.0% Fresh Whole Blood/Plasma, factory lot calibration (i-stat) b 6.9% Fresh Whole Blood/Plasma, previous clinical studies (i-stat) c 6.9% a Control fluids, factory lot calibration (i-stat) this is the total imprecision of a minimum of 24 cartridges per lot for 14 lots of i-stat ctni test cartridges pooled over 3 control levels and spanning 42 i-stat-1 handheld analyzers. b Fresh Whole Blood/Plasma, factory lot calibration (i-stat) this is the pooled withinsample imprecision of whole bloods and plasmas spiked with ctni (as ITC, HyTest TM, Finland). The calculated value spans 196 spiked whole bloods and plasmas (0.05 ng/ml < [ctni] < 45 ng/ml, N = 6 i-stat ctni test cartridges per fluid), 14 lots of i-stat ctni test cartridges, and 42 i-stat-1 handheld analyzers. c Fresh Whole Blood/Plasma, previous clinical studies (i-stat) this is the pooled within-sample imprecision for patient specimens exhibiting [ctni] > 0.2 ng/ml and being comprised of 189 whole blood samples and 189 plasma samples (N = 6 i-stat ctni test cartridges per fluid); results were generated using 6 lots of i-stat ctni test cartridges and 18 i-stat-1 handheld analyzers at 3 clinical sites at which data for the 510(k) submission were acquired. d Frozen-thawed sample imprecision from method comparison in the current evaluation The imprecision reported here is pooled over all pairwise points for which [ctni] > 0.08 ng/ml (upper 99 th percentile of reference range for the i-stat ctni assay). i-stat Lot Numbers ctni Test Cartridges: S03288 Controls Level 1: M30381 Level 2: M30382 Level 3: M30383 Calibration Verification: M3038SA Software: JAMS113/CLEW G93 i-stat Corporation - 7 -

8 References 1. D. Atar, L.H. Madsen, R. Labugger, J.E. VanEyk. Molecular modifications of troponin I and T detected in serum from patients with acute myocardial infarction [Article in Danish]; Ugeskr Laeger, 165:2, (2003) 2. D. Uettwiller-Geiger et al. Multicenter Evaluation of an Automated Assay for Troponin I; Clinical Chemistry, 48:6, (2002). 3. F.A. Apple et al. Multicenter Clinical and Analytical Evaluation of the AsSYM Troponin-I Immunoassay to Assist in the Diagnosis of Myocardial Infarction; Clinical Chemistry, 45:2, (1999). 4. P.O. Collinson et al., Measurement of cardiac troponins, Ann. Clin. Biochem. 38, (2001). 5. The Joint European Society of Cardiology/American College of Cardiology Committee; Myocardial infarction redefined - A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction, Eur. Heart J., 21:18, (2000). 6. i-stat ctni Cartridge and Test Information Sheet (copy attached). i-stat Corporation - 8 -

9 Raw Data Method Comparison Sample AxSYM #1 i-stat #1 i-stat # i-stat Corporation - 9 -

10 Raw Data Imprecision Sample ID Level Level Level mean sd %CV 4.9% 5.9% 5.3% Calibration Verification Run Level 1 Level 2 Level mean target range i-stat Corporation