(99 days)
The ChemTrak AccuMeter® Theophylline Test provides a rapid, noninstrumented enzyme immunochromatographic method for in vitro quantitative measurement of Theophylline concentrations in ambulatory patients using fingerstick whole blood, heparinized venous whole blood or serum. This test has not been validated for use with blood from neonates.
The AccuMeter Theophylline Test is a rapid immunoassay for the quantitative detection of theophylline, using HRP labeled anti-theophylline antibodies and immobilized monoclonal anti-theophylline antibodies. The immunospecific signal is measured by the height of the enzyme label along the test strip.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Metric (Implied) | Reported Device Performance |
|---|---|---|
| Accuracy (Correlation to Predicate) | Correlation Coefficient (R) for AccuMeter Fingerstick vs. TDx | 0.943 (from Table 1, "AccuMeter Compared to TDx Theophylline" for 102 observations) and 0.937 (from Table 2, "AccuMeter Fingerstick vs TDx" for 40 observations). |
| Correlation Coefficient (R) for AccuMeter Serum vs. TDx | 0.959 (from Table 2, "AccuMeter Serum vs TDx" for 39 observations) | |
| Correlation Coefficient (R) for AccuMeter Whole Blood vs. TDx | 0.963 (from Table 2, "AccuMeter Whole Blood vs TDx" for 39 observations) | |
| Precision | Within-Run % CV (Coefficient of Variation) | Level 1: 5.9% (Study 1), 7.7% (Study 2), 7.5% (Study 3) Level 2: 6.0% (Study 1), 6.0% (Study 2), 4.7% (Study 3) |
| Total % CV (Coefficient of Variation) | Level 1: 7.6% (Study 1), 7.8% (Study 2), 10.7% (Study 3) Level 2: 6.7% (Study 1), 7.6% (Study 2), 8.4% (Study 3) | |
| Sensitivity | Lower Limit of Detection | 5 ug/mL (The assay is sensitive enough to detect down to 5 ug/mL. Results <5 ug/mL should be reanalyzed by another method.) |
| Recovery | % Recovery at various concentrations | 8.3 µg/mL: 99.2% 12.5 µg/mL: 100.7% 16.6 µg/mL: 104.2% 20.7 µg/mL: 108.7% 24.8 µg/mL: 103.8% |
Note: The document explicitly states "The regression data demonstrates substantial equivalence, as well as the safety and effectiveness, of the AccuMeter Theophylline Test to the TDx Theophylline Assay." This implies that the achieved correlation coefficients and other performance metrics met the implicit acceptance criteria for substantial equivalence to the predicate device. Specific numerical thresholds for "acceptable" correlation, precision, or recovery are not explicitly stated.
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy (Table 1):
- Sample Size: 102 observations (patients where AccuMeter results were not below the detection limit and valid cassette runs).
- Data Provenance: Clinical studies conducted at three independent clinical sites. From patients receiving theophylline therapy and some theophylline-free subjects. IRB approval was obtained. Retro/Prospective: It is a prospective clinical study since patients were "recruited" and "informed consent was obtained."
- Accuracy (Table 2 - comparison of sample types):
- Sample Size: 40 patients for fingerstick vs TDx comparison, 39 patients for serum vs TDx, and 39 patients for whole blood vs TDx.
- Data Provenance: Conducted at one clinical site. Patients receiving theophylline therapy. Prospective, as mentioned.
- Precision:
- Sample Size:
- Study 1: 80 for Level 1, 80 for Level 2 (total 160 runs over 9-20 days).
- Study 2: 80 for Level 1, 80 for Level 2 (total 160 runs over 9-20 days).
- Study 3: 36 for Level 1, 36 for Level 2 (total 72 runs over 9-20 days).
- Data Provenance: Three field sites. Controls were tested over 9 to 20 days.
- Sample Size:
- Recovery:
- Sample Size: 10 replicates for each of the 5 concentrations (total 50 measurements).
- Data Provenance: Theophylline was spiked into whole blood, indicating a laboratory-based study rather than patient samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
- The ground truth for the accuracy studies was established by the TDx Theophylline Monoclonal II Assay, which is a widely accepted laboratory method (predicate device).
- The document does not state the number of experts or their qualifications involved in performing the TDx testing or interpreting its results. It mentions "TDx Theophylline testing was performed by a centralized reference laboratory," implying qualified personnel, but no specifics are given.
4. Adjudication Method for the Test Set
- None specified. For the accuracy studies, the TDx assay served as the reference standard, so there was no multi-reader human adjudication process for establishing ground truth as there might be in image-based AI studies.
- For the AccuMeter itself, it is a "noninstrumented enzyme immunochromatographic method" with "Visual Quantitative" detection. While human observation is required for reading the height of the enzyme label, the document doesn't describe any adjudication process for these readings.
5. 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
- No, an MRMC comparative effectiveness study was not done. This study is for a medical device (a rapid immunoassay for theophylline concentration), not an AI algorithm designed to assist human readers with interpretation. The device itself performs the measurement.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This device operates as a standalone test in the sense that it provides a direct quantitative measurement. While a human visually reads the result (height of the enzyme label), the core "algorithm" (the immunoassay process) is performing the measurement without direct human-in-the-loop interpretation of complex data. The document does not describe the device as having an AI algorithm.
7. The Type of Ground Truth Used
- The primary ground truth used for accuracy and comparison was the TDx Theophylline Monoclonal II Assay, which is a Fluorescence Polarization Immunoassay. This is a laboratory-based, quantitative reference method.
8. The Sample Size for the Training Set
- Not applicable / Not specified. This document describes the validation of a physical diagnostic assay (AccuMeter Theophylline Test), not a machine learning or AI algorithm that requires a "training set." The methodology is based on biochemical reactions.
9. How the Ground Truth for the Training Set was Established
- Not applicable. As a non-AI diagnostic device, there is no "training set" in the context of machine learning.
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Oct-01-97 02:49P ChemTrak, Inc.
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408 524 9464
P.03
Addridge
10/1/97 Amendment to 510(k) Number K972495 AccuMeter Theophylline Test
OCT 10 1997
510(k) Summary of Safety and Effectiveness Information Upon Which an Equivalence Determination Could Be Made October 1, 1997
| Device Name:Common Name: | AccuMeter® Theophylline TestTheophylline Test System |
|---|---|
| Intended Use: | The ChemTrak AccuMeter® Theophylline Test provides arapid, noninstrumented enzyme immunochromatographicmethod for in vitro quantitative measurement of Theophyllineconcentrations in ambulatory patients using fingerstick wholeblood, heparinized venous whole blood or serum. This test hasnot been validated for use with blood from neonates. |
| Device Description: | The AccuMeter Theophylline Test is a rapid immunoassayfor the quantitative detection of theophylline, using HRPlabeled anti-theophylline antibodies and immobilizedmonoclonal anti-theophylline antibodies. Theimmunospecific signal is measured by the height of theenzyme label along the test strip. |
| Device Class: | Class II |
| Classification Panel: | Clinical Toxicology Test Systems |
| Facility Address: | ChemTrak, Inc.929 East Arques AvenueSunnyvale, CA 94086-4520 |
| Contact Name: | SubbaRao Gunupudi, Ph.D.Vice President Research & Development |
| Telephone: | (408) 773-8156 |
| Fax: | (408) 773-1651 |
| Alternate Contact: | Mark DeLaurentisClinical Research Manager |
| Telephone: | (408) 773-8156 |
| Fax: | (408) 773-1651 |
| Predicate Device Name: | TDx®/TDxFLX® Theophylline Monoclonal IIAbbott Laboratories, Abbott Park, IL.510(k) Number: K932127 |
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Sample collection and clinical evaluation of the AccuMeter Theophylline Test were performed at three independent clinical sites. IRB approval was obtained for the study protocol. TDx Theophylline testing was performed by a centralized reference laboratory.
Clinical studies were conducted at three sites. A minimum of 40 subjects receiving theophylline therapy were recruited from the patient population at each site. Five to ten theophylline-free subjects were also recruited. Informed consent was obtained from all subjects. The following subject demographic and medical information was collected: age; sex: theophylline dose. Site 1 also tested serum and heparinized whole blood on the AccuMeter. Serum was sent to the reference laboratory for TDx theophylline results.
Accuracy
The accuracy of the AccuMeter Theophylline Test has been demonstrated by correlation to Fluorescence Polarization Immunoassay (TDx) using fingerstick and serum specimens in separate studies.
Testing was performed on individuals receiving theophylline therapy at three independent clinical sites. The least-squares linear regression analysis of all sites combined is shown below (Table 1). In 30 out of 149 patients the results were less than the AccuMeter detection limit and were not included for regression analysis. Of the 454 cassettes run on patient samples, the Add Developer Window did not turn green in 6 cassettes and the Control Window did not turn purple in 1 cassette.
| Y axis: | AccuMeter Fingerstick |
|---|---|
| X axis: | TDx |
| Slope | 1.05 |
| Intercept | -0.2 |
| Correlation Coefficient | 0.943 |
| Number of Observations | 102 |
Table 1: Accuracy -- AccuMeter Compared to TDx Theophylline
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10/1/97 Amendment to 510(k) Number K972495 AccuMeter Theophylline Test
The use of fingerstick whole blood, serum, and heparinized whole blood samples in the AccuMeter Theophylline Test was evaluated by parallel testing of 40 patients, by AccuMeter and TDx. at one clinical site. Testing was performed on individuals receiving theophylline therapy. Results of least-squares linear regression analysis are shown in Table 2.
| TheophyllineY Axis : | AccuMeterFingerstick | AccuMeterSerum | AccuMeterWhole Blood |
|---|---|---|---|
| X Axis : | TDx | TDx | TDx |
| Slope | 1.06 | 1.03 | 0.99 |
| Intercept | 0.4 | 0.4 | 1.1 |
| Correlation Coefficient | 0.937 | 0.959 | 0.963 |
| Number of Observations | 40 | 39 | 39 |
| Table 2: Comparison of AccuMeter Fingerstick, Serum and Whole Blood to TDx | ||
|---|---|---|
| Theophylling |
Precision
Precision studies were conducted at three field sites. Two levels of controls were tested twice per day in duplicate over a period of 9 to 20 days. Results appear in Table 3.
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| N* | Observed Meanµg/mL | SDµg/mL | % CV | |
|---|---|---|---|---|
| Study 1 | ||||
| Within Run | ||||
| Level 1 | 80 | 10.8 | 0.64 | 5.9 |
| Level 2 | 80 | 21.3 | 1.27 | 6.0 |
| Total | ||||
| Level 1 | 80 | 10.8 | 0.82 | 7.6 |
| Level 2 | 80 | 21.3 | 1.43 | 6.7 |
| Study 2 | ||||
| Within Run | ||||
| Level 1 | 80 | 10.4 | 0.80 | 7.7 |
| Level 2 | 80 | 22.6 | 1.34 | 6.0 |
| Total | ||||
| Level 1 | 80 | 10.4 | 0.82 | 7.8 |
| Level 2 | 80 | 22.6 | 1.72 | 7.6 |
| Study 3 | ||||
| Within Run | ||||
| Level 1 | 36 | 10.4 | 0.77 | 7.5 |
| Level 2 | 36 | 21.5 | 1.01 | 4.7 |
| Total | ||||
| Level 1 | 36 | 10.4 | 1.11 | 10.7 |
| Level 2 | 36 | 21.5 | 1.81 | 8.4 |
Table 3: Within-Run and Total Precision of AccuMeter Theophylline Test
*The Add Developer Window did not turn green in 8 AccuMeters and the Control Window did not turn purple in 1 AccuMeter.
Sensitivity
The sensitivity of the AccuMeter Theophylline assay is 5 ug/mL. Patient samples not containing theophylline may give results in the range 0 - 4.6 ug/mL. Patients whose blood gives a reading of <5 ug/mL should be reanalyzed by another method.
Recovery
Recovery for the AccuMeter Theophylline Test was determined by spiking theophylline into whole blood at five different concentrations (Table 4).
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| Table 4: Recovery of Theophylline in Whole Blood | |||
|---|---|---|---|
| Concentrationµg/mL | N | Meanµg/mL | Recovery(%) |
| 8.3 | 10 | 8.2 | 99.2 |
| 12.5 | 10 | 12.6 | 100.7 |
| 16.6 | 10 | 17.3 | 104.2 |
| 20.7 | 10 | 22.5 | 108.7 |
| 24.8 | 10 | 25.7 | 103.8 |
covery of Theophylline in Whole Blood D A. T
Substantial equivalence has been demonstrated between the AccuMeter Theophylline Test
ed the characterial concerner in Wasseleral U.Assoc. The characteristics Substantial equivalence nas ocen uchonsinuline Monoclonal II Assay. The characteristics of
and the Abbott TDx®/TDxFLX® Theophylline Monoclonal II Assay (TDx) are and the Abbott TDX&TDXF Theophylline Monoclonal II Assay (TDx) are summarized in Table 5.
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| Table 5: Comparison of the AccuMeter Theophylline Test to the TDx Theophylline | |
|---|---|
| Monoclonal II Assay (Predicate Device) |
| CharacteristicCompared | AccuMeterTheophylline(Test Method) | TDxTheophyllineMonoclonal II(Predicate Device) |
|---|---|---|
| Intended Use | "...provides a rapid,noninstrumented enzymeimmunochromatographicmethod for in vitroquantitative measurement oftheophylline concentrationsin ambulatory patients usingfingerstick whole blood,heparinized venous wholeblood or serum." | "... is a reagent system forthe quantitativemeasurement of theophyllinein serum or plasma." |
| Analyte | Theophylline | Theophylline |
| Methodology | Noninstrumented,Enzyme Immunochroma-tographic | Fluorescence PolarizationImmunoassay |
| Test Sample | Whole Blood or SerumNo Pretreatment | Serum or PlasmaNo Pretreatment |
| Test Components | Single-use CassetteColor Developer | Reagent KitCalibrator KitFluorometer |
| Assay Range | 5-30 µg/mL | 0.82-40 µg/mL |
| Method ofDetection | VisualQuantitative | SpectrophotometricQuantitative |
| Test Storage | Refrigerated | Refrigerated |
The regression data demonstrates substantial equivalence, as well as the safety and effectiveness, of the AccuMeter Theophylline Test to the TDx Theophylline Assay.
Prepared and Submitted October 1, 1997 Mark DeLaurentis Clinical Research Manager ChemTrak, Inc., 929 East Arques Avenue, Sunnyvale, CA 94086-4520
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Image /page/6/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the bird symbol. The text is in all capital letters and is in a sans-serif font.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
OCT 10 1997
SubbaRao Gunupudi, Ph.D. Vice President Research & Development ChemTrak, Inc. 929 East Arques Avenue Sunnyvale, California 94086
Re : K972495 Trade Name: AccuMeter® Theophylline Test Requlatory Class: II Product Code: KLS Dated: September 15, 1997 September 16, 1997 Received:
Dear Dr. Gunupudi:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth General in the Quality System Regulation (QS) for Medical Devices: regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Page of of
510(k) Number (if known): K972495
AccuMeter® Theophylline Test Device Name:
Indications For Use:
్లో
The AccuMeter® Theophylline Test is a rapid, noninstrumented enzyme immunochromatographic method for the in vitro quantitative measurement of theophylline concentrations in ambulatory patients using fingerstick whole blood, heparinized venous whole blood or serum. This test has not been validated for use with blood from neonates.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. 4972495
| Prescription Use | |
|---|---|
| (Per 21 CFR 801.109) |
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 862.3880 Theophylline test system.
(a)
Identification. A theophylline test system is a device intended to measure theophylline (a drug used for stimulation of the muscles in the cardiovascular, respiratory, and central nervous systems) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of theophylline overdose or in monitoring levels of theophylline to ensure appropriate therapy.(b)
Classification. Class II.