(161 days)
A software package and instrument interface that is used for quantitative analyses of high performance liquid chromatography (HPLC) test kits.
The CDM makes use of a 486 IBM compatible computer and a separate communications interface. The system accepts signals from a detector, integrates the chromatograms, identifies reference peaks and performs calculations of percent area. In addition, the CDM can control pumps and an automated sampler and store quality control data.
The provided document describes the Bio-Rad Laboratories Clinical Data Management (CDM) system, which is a software package and instrument interface used for quantitative analyses of high-performance liquid chromatography (HPLC) test kits. The study described aims to establish substantial equivalence of the CDM to existing predicate devices, specifically the Hewlett-Packard 3392A Reporting Integrator and, for analytical comparison, the Shimadzu CR501.
Acceptance Criteria and Reported Device Performance
The acceptance criterion implicitly is comparability to the existing Shimadzu CR501 integrator for analytical sensitivity and accuracy across various HPLC tests. The device performance is deemed acceptable if the results (standard deviation, coefficient of variation, correlation coefficient, y-intercept, and slope) are comparable to those obtained with the CR501.
| Test | Performance Metric | CR501 (Reference) | CDM (Device Performance) | Acceptance Criteria Met (Yes/No) |
|---|---|---|---|---|
| HVA by HPLC | Analytical Sensitivity (SD) | 0.018 | 0.020 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 3.6% | 4.0% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A (implied high) | 0.9999 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A (implied near 0) | 0.011 | Yes (Comparable) | |
| Accuracy (slope) | N/A (implied near 1) | 0.994 | Yes (Comparable) | |
| Urinary Metanephrines by HPLC | ||||
| Metanephrine | Analytical Sensitivity (SD) | 0.986 | 0.796 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 6.8% | 5.5% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.9999 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -1.074 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 1.017 | Yes (Comparable) | |
| Normetanephrine | Analytical Sensitivity (SD) | 1.118 | 1.345 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 6.0% | 7.6% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.9999 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -2.867 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 1.023 | Yes (Comparable) | |
| 3-Methoxytyramine | Analytical Sensitivity (SD) | 0.750 | 0.546 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 9.6% | 7.8% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.999 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -0.552 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 0.999 | Yes (Comparable) | |
| VMA by HPLC | Analytical Sensitivity (SD) | 0.010 | 0.010 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 1.9% | 1.9% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.9998 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -0.002 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 0.994 | Yes (Comparable) | |
| Plasma Catecholamines by HPLC | ||||
| Epinephrine | Analytical Sensitivity (SD) | 2.72 | 1.32 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 18% | 13% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.9998 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -2.90 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 0.979 | Yes (Comparable) | |
| Norepinephrine | Analytical Sensitivity (SD) | 5.04 | 3.74 | Yes (Comparable) |
| Analytical Sensitivity (CV) | 14% | 12% | Yes (Comparable) | |
| Accuracy (Correlation Coefficient) | N/A | 0.9999 | Yes (Comparable) | |
| Accuracy (y-intercept) | N/A | -4.43 | Yes (Comparable) | |
| Accuracy (slope) | N/A | 1.003 | Yes (Comparable) | |
| Benzodiazepines by HPLC | Mean Analytical Sensitivity (SD) | 1.64 | 1.59 | Yes (Comparable) |
| Mean Analytical Sensitivity (CV) | 6.44% | 5.92% | Yes (Comparable) | |
| Mean Accuracy (Correlation Coefficient) | N/A | 0.9998 | Yes (Comparable) | |
| Mean Accuracy (y-intercept) | N/A | -0.156 | Yes (Comparable) | |
| Mean Accuracy (slope) | N/A | 0.9982 | Yes (Comparable) | |
| Tricyclic Antidepressants by HPLC | Mean Analytical Sensitivity (SD) | 1.37 | 1.24 | Yes (Comparable) |
| Mean Analytical Sensitivity (CV) | 5.23% | 4.74% | Yes (Comparable) | |
| Mean Accuracy (Correlation Coefficient) | N/A | 0.9997 | Yes (Comparable) | |
| Mean Accuracy (y-intercept) | N/A | 4.25 | Yes (Comparable) | |
| Mean Accuracy (slope) | N/A | 0.955 | Yes (Comparable) |
1. Sample sizes used for the test set and the data provenance:
The document does not explicitly state the sample sizes (e.g., number of specimens or chromatograms) used for the analytical comparison. It mentions "each of the following five tests" and provides sensitivity and accuracy data for various analytes within these tests. The data provenance is not specified, but it implies a laboratory setting where these HPLC tests were performed. It is a retrospective analysis of the device's performance against a comparative device rather than a prospective clinical study involving patient data.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
This study is an analytical comparison of two laboratory instruments (integrators) for quantitative analysis. The "ground truth" here is the quantitative analytical results obtained by a well-established and accepted method (Shimadzu CR501 integrator). Therefore, there were no human experts establishing a "ground truth" in the diagnostic sense (like radiologists interpreting images). The accuracy is measured against the output of the reference instrument.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This is an analytical device comparison, not a diagnostic study requiring adjudication of expert interpretations.
4. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is not an AI-assisted diagnostic study or an MRMC study. It's a comparison of two analytical instruments.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, this study represents a standalone comparison of the CDM system's performance (algorithm-driven integration and calculation) against another standalone instrument (CR501 integrator). There is no "human-in-the-loop performance" in evaluating the integrators' quantitative outputs. The humans operate the HPLC systems, but the comparison is on the data processing output.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" is established by the analytical measurements and calculations performed by the well-accepted and commercially available Shimadzu CR501 integrator. This is an analytical reference standard rather than a clinical ground truth like pathology or expert consensus. The assumption is that the CR501 provides accurate and precise measurements.
7. The sample size for the training set:
Not applicable. This document describes a performance evaluation of a device, not the development or training of a machine learning algorithm. The CDM is a "Clinical Data Management System" that performs calculations, integration, and control, rather than a learning AI system requiring a specific training set as understood in modern AI.
8. How the ground truth for the training set was established:
Not applicable, as there is no mention of a training set for an AI algorithm.
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Image /page/0/Picture/0 description: The image shows the logo for BIO-RAD. The logo is white text on a black background. The text is in a bold, sans-serif font. The logo is enclosed in a rounded rectangle.
Bio-Rad Laboratories
Diagnostics Group 4000 Alfred Nobel Drive Hercules, California 94547 1elephone: 510 724-7000 fax: 510 741-5824
SUMMARY OF SAFETY AND EFFECTIVENESS
Submitter: Bio-Rad Laboratories, Inc. Clinical Systems Division 4000 Alfred Nobel Hercules. California 94547 Phone 1 510 741-6015 Fax 1 510 741-5824
K9603922
JUL - 8 1988
Contact Person: Kenneth J. Kisco Specialist, Regulatory Affairs
Date prepared: January 25, 1996
Product Trade Name: CDM™
Common Name: Clinical Data Management System
Classification Name: Calculator/Data Processing Module, for Clinical use, 75 JQP
To establish substantial equivalence to an existing predicate device, the CDM has been compared to the Hewlett-Packard 3392A Reporting Integrator (K833113). A review of the intended use of each system shows them to be essentially the same. The intended use of the CDM is stated as: A software package and instrument interface that is used for quantitative analyses of high performance liquid chromatography (HPLC) test kits. The intended use of the 3392A Reporting Integrator is stated as: The 3392A is a multipurpose instrument that may be used for qualitative or quantitative analyses in many applications (see Appendix I).
A comparison of the technical features of the CDM and 3392A show the devices to be very similar. The CDM makes use of a 486 IBM compatible computer and a separate communications interface. The system is described in detail in Appendix C. In brief, the CDM accepts signals from a detector, integrates the chromatograms, identifies reference peaks and performs calculations of percent area. In addition, the CDM can control pumps and an automated sampler and store quality control data.
The predicate device, the H-P 3392A, is a CPU device with communication capability. Again. the 3392A accepts signals from a detector, integrates the chromatograms, identifies reference peaks and performs calculations of percent area. In addition, the 3392A can control an automated sampler. A complete comparison of the CDM and the predicate 3392A is summarized in Appendix D.
An analytical comparison of the CDM and the Shimadzu CR501 was done for each of the following five tests: 1) HVA by HPLC 2) Urinary Metanephrines by HPLC, 3) VMA by HPLC, 4) Plasma Catecholamines by HPLC, 5) Benzodiazepines & Tricyclic Antidepressants by HPLC.
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First, using the HVA by HPLC test, analytical sensitivity was: CR501 SD 0.018, CV 3.6%; CDM SD 0.020 CV 4.0%. Accuracy using HVA by HPLC test yielded a correlation coefficient of 0.9999, a y-intercept of 0.011, and a slope of 0.994. The HVA by HPLC test results for analytical sensitivity and method comparison given by the Clinical Data Management (CDM) System are comparable to those obtained using the CR501 integrator.
Second. using the urinary metanephrines by HPLC test for analytical sensitivity yielded the following: Metanephrine CR501 SD 0.986, CV 6.8%; Metanephrine CDM SD 0.796, CV 5.5%; Normetanephrine CR501 SD 1.118. CV 6.0%: Normetanephrine CDM SD 1.345 CV 7.6%; 3-Methoxytyramine CR501 SD 0.750, CV 9.6%; 3-Methoxytyramine CDM SD 0.546 CV 7.8%. CDM accuracy using the urinary metanephrines by HPLC was: Metanephrine CDM yielded a correlation coefficient of 0.9999, a v-intercept of -1.074, and a slope of 1.017; Normetanephrine CDM yeilded a correlation coefficient of 0.9999, a y-intercept of -2.867, and a slope of 1.023; 3-Methoxytyramine CDM yielded a correlation coefficient of 0.999, a y-intercept of -0.552, and a slope of 0.999. The urinary metanephrines by HPLC test results for sensitivity and method comparison given by the Clinical Data Management (CDM) System are comparable to those using the CR501 integrator
Third, using the VMA by HPLC test, analytical sensitivity was: CR501 VMA SD 0.010, CV 1.9%; CDM VMA SD 0.010, CV 1.9%. CDM VMA yielded a correlation coefficient of 0.9998, a yintercept of -0.002, and a slope of 0.994 The VMA by HPLC results for analytical sensitivity and method comparison given by the Clinical Data Management (CDM) System are comparable to those using the CR501 integrator.
Fourth, using the Plasma Catecholamines by HPLC test, analytical sensitivity was: Epinephrine CR501 SD 2.72, CV 18%; Epinephrine CDM SD 1.32, CV 13%; Norepinephrine CR501 SD 5.04.CV 14%: Norepinephrine CDM SD 3.74. CV 12%. Epinephrine CDM veilded a correlation coefficient 0.9998, a v-intercept -2.90, and a slope 0.979 and Norepinephrine CDM veilded a correlation coefficient 0.9999, a y-intercept -4.43, and a slope 1.003. The Plasma Catcholamines by HPLC test results for sensitivity and response comparison given by the Clinical Data Management (CDM) System are comparable to those using the CR501 integrator.
The fifth test used the bezodiazepines & tricyclic antidepressants by HPLC. Each of these tests measure mulitple analytes. The following data represent the means of the sensitivity and accuracy results. Using the Benzodiazepine by HPLC test method analytical sensitivity was: a mean CR501 SD 1.64; a mean CR501 CV 6.44%; a mean CDM SD 1.59; a mean CDM CV 5.92%. Accuracy for the Benzodiazepine by HPLC test method was: a mean correlation coefficient of 0.9998, a mean y-intercept -0.156, and a mean slope 0.9982.
Using the tricyclic antidepressants by HPLC test method, analytical sensitivity was: CR501 a mean SD 1.37 a mean CV 5.23%; CDM a mean SD 1.24 and a mean CV 4.74%. Accuracy for the tricyclic antidepressants by HPLC test method was: a mean correlation coefficient of 0.9997, a mean y-intercept 4.25 and a mean slope 0.955.
Equivalence was shown between the Clinical Data Management (CDM) system and the CR501 integrator in testing the following: 1) HVA by HPLC 2) Urinary Metanephrines by HPLC, 3) VMA by HPLC, 4) Plasma Catecholamines by HPLC, 5) Benzodiazepines & Tricyclic Antidepressants by HPLC.
§ 862.2260 High pressure liquid chromatography system for clinical use.
(a)
Identification. A high pressure liquid chromatography system for clinical use is a device intended to separate one or more drugs or compounds from a solution by processing the mixture of compounds (solutes) through a column packed with materials of uniform size (stationary phase) under the influence of a high pressure liquid (mobile phase). Separation of the solutes occurs either by absorption, sieving, partition, or selective affinity.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.