(88 days)
Not Found
No
The description focuses on a standard immunoassay technology (CMIA) and its analytical performance characteristics. There is no mention of AI or ML in the device description, intended use, or performance studies.
No
This device is an in vitro diagnostic (IVD) assay designed to aid in the diagnosis of myocardial infarction by measuring cardiac troponin I levels, not to directly treat or mitigate a disease.
Yes
The intended use explicitly states that the device "is to be used as an aid in the diagnosis of myocardial infarction (MI)".
No
The device is a chemiluminescent microparticle immunoassay (CMIA) which is a laboratory-based assay system involving reagents, microparticles, and an instrument (ARCHITECT i2000SR System) to measure a biomarker. This is a hardware-based system with associated software, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is used for the "quantitative determination of cardiac troponin I (cTnl) in human plasma" and is to be used "as an aid in the diagnosis of myocardial infarction (MI)." This clearly indicates that the device is intended to be used in vitro (outside the body) to examine a specimen (human plasma) to provide information for diagnostic purposes (aiding in the diagnosis of MI).
- Device Description: The description details a "chemiluminescent microparticle immunoassay (CMIA)" which is a laboratory-based test performed on biological samples.
- Specimen Type: The assay is performed on "human plasma," which is a biological specimen collected from a patient.
- Performance Studies: The document describes extensive "Nonclinical Performance" studies (precision, linearity, limits of measurement, analytical specificity) and "Clinical Performance" studies (diagnostic accuracy using patient samples) which are standard for IVD devices to demonstrate their analytical and clinical validity.
All these elements align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The ARCHITECT STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnI) in human plasma (dipotassium [K2] EDTA) on the ARCHITECT i2000SR System.
The ARCHITECT STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
Product codes (comma separated list FDA assigned to the subject device)
MMI
Device Description
The ARCHITECT STAT High Sensitivity Troponin-I reagent kit contains:
- Microparticles: 1 bottle (6.6 mL per 100 test bottle / 29.0 mL per 500 test bottle) Anti-troponin I (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.035% solids. Preservative: ProClin 300.
- Conjugate: 1 bottle (5.9 mL per 100 test bottle / 28.5 mL per 500 test bottle). Anti-troponin I (mouse-human chimeric, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer and human IgG. Minimum concentration: 0.1 mg/L. Preservative: ProClin 300.
Principles of the Procedure
The ARCHITECT STAT High Sensitivity Troponin-I assay is a two-step immunoassay for the quantitative determination of cardiac troponin I in human plasma (dipotassium EDTA) using chemiluminescent microparticle immunoassay technology with flexible assay protocols, referred to as Chemiflex.
-
- Sample and anti-troponin I antibody-coated paramagnetic microparticles are combined. The cTnI present in the sample binds to the anti-troponin I coated microparticles.
-
- After incubation and wash, anti-troponin I acridinium-labeled conjugate is added.
-
- Following another wash cycle, Pre-Trigger and Trigger Solutions are added to the reaction mixture.
-
- The resulting chemiluminescent reaction is measured as relative light units (RLUs). There is a direct relationship between the amount of cTnI in the sample and the RLUs detected by the ARCHITECT iSystem optics.
The cTnI concentration is read relative to a standard curve established with calibrators of known cTnI concentrations.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision (Reproducibility):
- Study Type: Reproducibility study using 1 lot of reagent, calibrators, and controls. Performed over a minimum of 3 days on each of 3 instruments.
- Sample Size: 10 samples (12 replicates each).
- Key Results:
- Sample 1 (5.3 ng/L): Within-Run %CV 2.2, Within-Laboratory %CV 4.8, Reproducibility %CV 4.8
- Sample 2 (11.2 ng/L): Within-Run %CV 4.2, Within-Laboratory %CV 4.2, Reproducibility %CV 5.5
- Sample 3 (17.5 ng/L): Within-Run %CV 2.9, Within-Laboratory %CV 3.1, Reproducibility %CV 4.6
- Sample 4 (18.8 ng/L): Within-Run %CV 3.2, Within-Laboratory %CV 3.4, Reproducibility %CV 4.0
- Sample 5 (34.6 ng/L): Within-Run %CV 2.4, Within-Laboratory %CV 2.4, Reproducibility %CV 3.2
- Sample 6 (38.8 ng/L): Within-Run %CV 2.6, Within-Laboratory %CV 3.8, Reproducibility %CV 5.0
- Sample 7 (45.0 ng/L): Within-Run %CV 3.4, Within-Laboratory %CV 4.6, Reproducibility %CV 7.0
- Sample 8 (163.7 ng/L): Within-Run %CV 3.1, Within-Laboratory %CV 4.9, Reproducibility %CV 7.1
- Sample 9 (167.5 ng/L): Within-Run %CV 4.1, Within-Laboratory %CV 4.4, Reproducibility %CV 6.6
- Sample 10 (179.6 ng/L): Within-Run %CV 3.8, Within-Laboratory %CV 3.8, Reproducibility %CV 4.6
Within-Laboratory Precision:
- Study Type: Based on CLSI EP05-A2. Conducted using 3 reagent lots, 2 calibrator lots, 1 control lot, Bio-Rad controls, and 2 instruments. Five controls tested in duplicate, twice per day for 20 days.
- Key Results:
- Low Control (19.3-20.4 ng/L): Within-Run %CV 3.0-4.1, Within-Laboratory %CV 3.7-4.3
- Medium Control (190.7-197.8 ng/L): Within-Run %CV 1.8-2.7, Within-Laboratory %CV 2.1-3.1
- Bio-Rad Level Low (43.3-46.4 ng/L): Within-Run %CV 2.8-3.9, Within-Laboratory %CV 3.2-4.0
- Bio-Rad Level 2 (1198.0-1309.6 ng/L): Within-Run %CV 2.2-3.0, Within-Laboratory %CV 2.5-3.4
- Bio-Rad Level 3 (2812.3-3138.2 ng/L): Within-Run %CV 1.8-3.1, Within-Laboratory %CV 2.7-3.4
Lower Limits of Measurement:
- Study Type: Based on CLSI EP17-A2. Testing of zero-analyte samples (4 reagent lots, 5 instruments, min 3 days) and low-analyte samples (2 reagent lots, 2 instruments, min 3 days).
- Key Results:
- LoB: 0.9 ng/L
- LoD: 1.7 ng/L
- LoQ: 3.5 ng/L (analytical measuring interval alignment); Observed LoQ on ARCHITECT i2000SR System was 2.3 ng/L (20 %CV).
Linearity:
- Study Type: Based on CLSI EP06-A.
- Key Results: Linear across the analytical measuring interval of 3.5 to 5000.0 ng/L.
Analytical Specificity (Interference):
- Study Type: Based on CLSI EP07-A2. Each substance/drug tested at 2 analyte levels (approx. 15 ng/L and 500 ng/L).
- Key Results:
- Endogenous Substances: No significant interference (within ± 10%) observed for Unconjugated Bilirubin (≤ 20 mg/dL), Conjugated Bilirubin (≤ 20 mg/dL), Hemoglobin (≤ 500 mg/dL), Total Protein (≤ 9.3 g/dL), Triglycerides (≤ 3000 mg/dL). Interference beyond ± 10% observed for Total Protein at 12.4 g/dL (decreased troponin values by -12.0% at 15 ng/L and -18.4% at 500 ng/L).
- Drugs: No significant interference (within ± 10%) observed for a wide range of commonly used pharmaceuticals and cardiac-specific drugs at therapeutic and high levels, with the exception of fibrinogen.
- Fibrinogen: Interference beyond ± 10% observed at 1000 mg/dL (11.6% increase at 15 ng/L). Specimens with elevated fibrinogen may show falsely elevated values.
- Clinical Conditions: 23 specimens positive for HAMA and 23 for RF evaluated. Assay results may be impacted by HAMA, heterophilic antibodies, and RF, potentially leading to falsely elevated or depressed values. Troponin autoantibodies may lead to falsely low troponin assay results.
Cross-Reactants:
- Study Type: Based on CLSI EP07-A2. Samples with cTnI concentrations from 3.5 to 5000 ng/L containing cross-reactants were tested.
- Key Results: Observed % cross-reactivity was
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.
0
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September 13, 2019
Abbott Laboratories Diagnostic Division Judi Wallach Regulatory Affairs Project Manager Dept. 09AA. Bldg. AP8-1. 100 Abbott Park Road Abbott Park, IL 60064-6038
Re: K191595
Trade/Device Name: ARCHITECT STAT High Sensitivity Troponin-I Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: June 13, 2019 Received: June 17, 2019
Dear Judi Wallach:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K191595
Device Name ARCHITECT STAT High Sensitivity Troponin-I
Indications for Use (Describe)
The ARCHITECT STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnl) in human plasma (dipotassium [K2] EDTA) on the ARCHITECT i2000SR System.
The ARCHITECT STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary (Summary of Safety and Effectiveness)
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
I. 510(k) Number
II. Applicant Name
Abbott Laboratories Diagnostics Division Dept. 9AA, AP8-1 100 Abbott Park Road Abbott Park, IL 60064
Primary contact person for all communications:
Judi Wallach, ADD, Regulatory Affairs Project Manager Telephone Number: (224) 667-1132 Fax Number: (224) 667-4836 E-Mail: judith.r.wallach@abbott.com Date summary prepared: August 14, 2019
Secondary contact person for all communications:
Grace LeMieux ADD, Director, Regulatory Affairs Telephone Number: (224) 668-0409 E-Mail: grace.lemieux@abbott.com
III. Device Name
ARCHITECT STAT High Sensitivity Troponin-I
Reagents
Trade Name: ARCHITECT STAT High Sensitivity Troponin-I Device Classification: Class II Classification Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Governing Regulation: 862.1215
Code: MMI
4
IV. Predicate Device
Reagents
Elecsys Troponin T Gen 5 STAT Immunoassay (K162895)
V. Description of Device
Reagents
The ARCHITECT STAT High Sensitivity Troponin-I reagent kit contains:
- . Microparticles: 1 bottle (6.6 mL per 100 test bottle / 29.0 mL per 500 test bottle) Anti-troponin I (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.035% solids. Preservative: ProClin 300.
- . Conjugate: 1 bottle (5.9 mL per 100 test bottle / 28.5 mL per 500 test bottle). Anti-troponin I (mouse-human chimeric, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer and human IgG. Minimum concentration: 0.1 mg/L. Preservative: ProClin 300.
Principles of the Procedure
The ARCHITECT STAT High Sensitivity Troponin-I assay is a two-step immunoassay for the quantitative determination of cardiac troponin I in human plasma (dipotassium EDTA) using chemiluminescent microparticle immunoassay technology with flexible assay protocols, referred to as Chemiflex.
-
- Sample and anti-troponin I antibody-coated paramagnetic microparticles are combined. The cTnI present in the sample binds to the anti-troponin I coated microparticles.
-
- After incubation and wash, anti-troponin I acridinium-labeled conjugate is added.
-
- Following another wash cycle, Pre-Trigger and Trigger Solutions are added to the reaction mixture.
-
- The resulting chemiluminescent reaction is measured as relative light units (RLUs). There is a direct relationship between the amount of cTnI in the sample and the RLUs detected by the ARCHITECT iSystem optics.
The cTnI concentration is read relative to a standard curve established with calibrators of known cTnI concentrations.
5
VI. Intended Use of the Device
The ARCHITECT STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnI) in human plasma (dipotassium [K₂] EDTA) on the ARCHITECT i2000SR System.
The ARCHITECT STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
VII. Comparison of Technological Characteristics
The ARCHITECT STAT High Sensitivity Troponin-I assay (candidate assay) utilizes a CMIA methodology for the quantitative in vitro determination of cTnI and is intended for use on the ARCHITECT i2000SR System.
The similarities and differences between the candidate assay and the predicate assay are presented in the following table.
| Characteristics | Candidate Device
ARCHITECT STAT High Sensitivity
Troponin-I | Predicate Device
Roche cobas Elecsys Troponin T
Gen 5 STAT
(K162895) |
|------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Platform | ARCHITECT i2000SR | cobas e 411 and e 601 immunoassay
analyzers |
| Methodology | CMIA | Electrochemiluminescence
Immunoassay (ECLIA) |
| Intended Use and
Indications for Use | The ARCHITECT STAT High Sensitivity
Troponin-I assay is a chemiluminescent
microparticle immunoassay (CMIA) used
for the quantitative determination of
cardiac troponin I (cTnI) in human plasma
(dipotassium [K2] EDTA) on the
ARCHITECT i2000SR System.
The ARCHITECT STAT High Sensitivity
Troponin-I assay is to be used as an aid in
the diagnosis of myocardial infarction
(MI). | Immunoassay for the in vitro
quantitative determination of cardiac
troponin T (cTnT) in lithium heparin
plasma. The immunoassay is intended
to aid in the diagnosis of myocardial
infarction.
The electrochemiluminescence
immunoassay "ECLIA" is intended for
use on the cobas system analyzers. |
| Specific Analyte
Detected | cTnI | cTnT |
| Characteristics | Candidate Device
ARCHITECT STAT High Sensitivity
Troponin-I | Predicate Device
Roche cobas Elecsys Troponin T
Gen 5 STAT
(K162895) |
| Specimen Type | Plasma (K2 EDTA) | Plasma (lithium heparin) |
| Reagent Components | Microparticles – Anti-troponin I (mouse,
monoclonal) coated microparticles in TRIS
buffer with protein (bovine) stabilizer.
Minimum concentration: 0.035% solids.
Preservative: ProClin 300.
Conjugate - Anti-troponin I
(mouse-human chimeric, monoclonal)
acridinium-labeled conjugate in MES
buffer with protein (bovine) stabilizer and
human IgG. Minimum concentration:
0.1 mg/L. Preservative: ProClin 300. | M - Streptavidin-coated microparticles
(transparent cap), 1 bottle, 6.5 mL:
Streptavidin-coated microparticles
0.72 mg/mL; preservative.
R1 - Anti-troponin T-Ab~biotin (gray
cap), 1 bottle, 8 mL: Biotinylated
monoclonal anti-cardiac troponin
T-antibody (mouse) 2.5 mg/L;
phosphate buffer 100 mmol/L, pH 6.0;
preservative; inhibitors.
R2 - Anti-troponin
T-Ab-Ru(bpy)2+(black cap), 1 bottle,
8 mL: Monoclonal chimeric
anti-cardiac troponin T-antibody
(mouse/human) labeled with ruthenium
complex 2.5 mg/L; phosphate buffer
100 mmol/L, pH 6.0; preservative. |
| Limit of Quantitation
(LoQ) | The LoQ is 3.5 ng/L. | The LoQ at ≤ 20 %CV is 6.0 ng/L. |
| Measurement Range | Analytical measuring interval (AMI):
3.5 to 5000.0 ng/L (pg/mL) | 6.0 to 10,000 ng/L |
| Potentially
Interfering
Endogenous
Substances and
Clinical Conditions | Samples targeted to 15 and 500 ng/L cTnI
were evaluated with unconjugated and
conjugated bilirubin (20 mg/dL),
hemoglobin (500 mg/dL), total protein
(9.3 g/dL) and triglycerides (3000 mg/dL).
No significant interference (interference
within ± 10%) was observed. | Samples from approximately 13 to
8500 ng/L cTnT were evaluated with
bilirubin (25 mg/dL), hemoglobin
(100 mg/dL), lipemia / Intralipid
(1500 mg/dL), human serum albumin
(7 g/dL), cholesterol (310 mg/dL),
biotin (20 ng/mL), rheumatoid factor
(RF) (900 IU/mL), and human
anti-mouse antibodies (HAMA)
(322 µg/L). Bias less than 10% was
observed. |
| Drug Interferences
(General Drug and
Cardiac Drug Panel) | Commonly used pharmaceuticals and
cardiac-specific drugs were evaluated with
samples targeted to 15 and 500 ng/L cTnI.
No significant interference (interference
within ± 10%) was observed at therapeutic
levels, and no significant interference
(interference within ± 10%) was observed
at high levels, with the exception of
fibrinogen. | Commonly used pharmaceuticals were
evaluated in samples with cTnT
concentrations of 15 ng/L and
9800 ng/L. Cardiac-specific drugs were
tested in samples with cTnT
concentrations of 15 ng/L and
1900 ng/L. Bias less than ± 10% was
observed. |
| Characteristics | Candidate Device
ARCHITECT STAT High Sensitivity
Troponin-I | Predicate Device
Roche cobas Elecsys Troponin T
Gen 5 STAT
(K162895) |
| 99th Percentile
Cutoff / Expected
Values from
Apparently Healthy
Individuals | Female: 17 ng/L (pg/mL)
Male: 35 ng/L (pg/mL)
Overall: 28 ng/L (pg/mL) | Female: 14 ng/L
Male: 22 ng/L
Overall: 19 ng/L |
Similarities and Differences
6
7
VIII. Summary of Nonclinical Performance
A. Precision
Reproducibility
A study was performed using 1 lot of the ARCHITECT STAT High Sensitivity Troponin-I reagent, 1 lot of the ARCHITECT STAT High Sensitivity Troponin-I Calibrators, and 1 lot of the ARCHITECT STAT High Sensitivity Troponin-I Controls. The study was performed to include K2 EDTA plasma specimens within each of 4 concentration ranges (> LoQ to 6 ng/L, 10 to 20 ng/L, 30 to 50 ng/L, and 150 to 200 ng/L). Only one specimen per concentration range was collected in a single day. The study was performed over a minimum of 3 days. Each specimen was stored at room temperature and tested in duplicate, twice in one day, on each of 3 instruments (for a total of 12 replicates) within 8 hours of collection.
| | | | Within-Run | | Between-
Run | | Within-
Laboratoryª | | Reproducibilityb | |
|-----------|----|----------------|------------|-----|-----------------|-----|------------------------|-----|------------------|-----|
| Sample | n | Mean
(ng/L) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 12 | 5.3 | 0.12 | 2.2 | 0.23 | 4.2 | 0.25 | 4.8 | 0.25 | 4.8 |
| Sample 2 | 12 | 11.2 | 0.47 | 4.2 | 0.00 | 0.0 | 0.47 | 4.2 | 0.62 | 5.5 |
| Sample 3 | 12 | 17.5 | 0.50 | 2.9 | 0.23 | 1.3 | 0.55 | 3.1 | 0.81 | 4.6 |
| Sample 4 | 12 | 18.8 | 0.60 | 3.2 | 0.22 | 1.2 | 0.64 | 3.4 | 0.75 | 4.0 |
| Sample 5 | 12 | 34.6 | 0.84 | 2.4 | 0.00 | 0.0 | 0.84 | 2.4 | 1.10 | 3.2 |
| Sample 6 | 12 | 38.8 | 1.00 | 2.6 | 1.10 | 2.8 | 1.48 | 3.8 | 1.92 | 5.0 |
| Sample 7 | 12 | 45.0 | 1.52 | 3.4 | 1.42 | 3.2 | 2.08 | 4.6 | 3.16 | 7.0 |
| Sample 8 | 12 | 163.7 | 5.00 | 3.1 | 6.23 | 3.8 | 7.99 | 4.9 | 11.68 | 7.1 |
| Sample 9 | 12 | 167.5 | 6.82 | 4.1 | 2.82 | 1.7 | 7.38 | 4.4 | 11.09 | 6.6 |
| Sample 10 | 12 | 179.6 | 6.76 | 3.8 | 0.00 | 0.0 | 6.76 | 3.8 | 8.19 | 4.6 |
4 Includes within-run and between-run variability.
b Includes within-run, between-run, and between-instrument variability.
8
Within-Laboratory Precision
A study was performed based on guidance from Clinical and Laboratory Standards Institute (CLSI) EP05-A2. Testing was conducted using 3 lots of the ARCHITECT STAT High Sensitivity Troponin-I reagent, 2 lots of the ARCHITECT STAT High Sensitivity Troponin-I Calibrators, 1 lot of the ARCHITECT STAT High Sensitivity Troponin-I Controls, 1 lot each of Bio-Rad Liquichek Cardiac Markers Plus Control LT (Level Low, 2, and 3), and 2 instruments. Five controls were tested in duplicate, twice per day on 20 days, following the manufacturers' storage and handling requirements.
Note: Patient samples can only be stored for 8 hours at room temperature; therefore, 20-day precision was conducted with quality controls. Bio-Rad controls were thawed and tested each day of the precision study.
Clinical and Laboratory Standards Institute (CLSI). Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition. CLSI Document EP05-A2. Wayne, PA: CLSI; 2004.
9
| | | Reagent
Lot | n | Mean
(ng/L) | Within-Run | | Within-
Laboratory
(Total)a | |
|-----------------|------------|----------------|----|----------------|------------|-----|-----------------------------------|-----|
| Sample | Instrument | | | | SD | %CV | SD | %CV |
| Low Control | 1 | 1 | 80 | 19.3 | 0.61 | 3.2 | 0.72 | 3.7 |
| | | 2 | 80 | 20.3 | 0.61 | 3.0 | 0.78 | 3.9 |
| | | 3 | 80 | 19.7 | 0.64 | 3.3 | 0.78 | 3.9 |
| | 2 | 1 | 80 | 20.4 | 0.84 | 4.1 | 0.85 | 4.1 |
| | | 2 | 80 | 20.2 | 0.64 | 3.2 | 0.83 | 4.1 |
| | | 3 | 80 | 20.0 | 0.66 | 3.3 | 0.87 | 4.3 |
| Medium Control | 1 | 1 | 80 | 190.7 | 4.21 | 2.2 | 5.54 | 2.9 |
| | | 2 | 80 | 195.0 | 3.57 | 1.8 | 4.13 | 2.1 |
| | | 3 | 80 | 191.2 | 4.27 | 2.2 | 4.49 | 2.3 |
| | 2 | 1 | 80 | 197.8 | 5.26 | 2.7 | 5.76 | 2.9 |
| | | 2 | 80 | 196.8 | 4.65 | 2.4 | 5.36 | 2.7 |
| | | 3 | 80 | 194.3 | 4.43 | 2.3 | 5.95 | 3.1 |
| Bio-Rad Level | 1 | 1 | 80 | 43.3 | 1.27 | 2.9 | 1.46 | 3.4 |
| Low | | 2 | 80 | 46.1 | 1.48 | 3.2 | 1.57 | 3.4 |
| | | 3 | 80 | 45.4 | 1.27 | 2.8 | 1.51 | 3.3 |
| | 2 | 1 | 80 | 45.2 | 1.36 | 3.0 | 1.82 | 4.0 |
| | | 2 | 80 | 46.4 | 1.80 | 3.9 | 1.84 | 4.0 |
| | | 3 | 80 | 46.0 | 1.40 | 3.0 | 1.48 | 3.2 |
| Bio-Rad Level 2 | 1 | 1 | 80 | 1198.0 | 31.13 | 2.6 | 33.80 | 2.8 |
| | | 2 | 80 | 1281.3 | 33.38 | 2.6 | 40.95 | 3.2 |
| | | 3 | 80 | 1267.1 | 27.57 | 2.2 | 31.72 | 2.5 |
| | 2 | 1 | 80 | 1260.1 | 38.34 | 3.0 | 42.33 | 3.4 |
| | | 2 | 80 | 1309.1 | 28.25 | 2.2 | 42.68 | 3.3 |
| | | 3 | 80 | 1309.6 | 35.68 | 2.7 | 43.81 | 3.3 |
| Bio-Rad Level 3 | 1 | 1 | 80 | 2812.3 | 64.56 | 2.3 | 80.50 | 2.9 |
| | | 2 | 80 | 3023.0 | 83.52 | 2.8 | 93.82 | 3.1 |
| | | 3 | 80 | 3015.3 | 94.13 | 3.1 | 95.14 | 3.2 |
| | 2 | 1 | 80 | 2978.3 | 80.34 | 2.7 | 102.42 | 3.4 |
| | | 2 | 80 | 3103.9 | 83.93 | 2.7 | 96.25 | 3.1 |
| | | 3 | 80 | 3138.2 | 55.49 | 1.8 | 84.50 | 2.7 |
4 Includes within-run, between-run, and between-day variability.
10
B. Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2. T Testing of zero-analyte samples was conducted using 4 lots of the ARCHITECT STAT High Sensitivity Troponin-I reagent kit across 5 instruments over a minimum of 3 days. Testing of low-analyte samples was conducted using 2 lots of the ARCHITECT STAT High Sensitivity Troponin-I reagent kit on each of 2 instruments over a minimum of 3 days. The limit of blank (LoB), limit of detection (LoD), and LoQ values are summarized below.
| ng/L (pg/mL) | |
|---|---|
| LoBa | 0.9 |
| LoDb | 1.7 |
| LoQc | 3.5 |
a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
c The LoQ presented in the table is in alignment with the low end of the AMI for the ARCHITECT STAT High Sensitivity Troponin-I assay. The observed LoQ on the ARCHITECT i2000SR System was 2.3 ng/L (2.3 pg/mL). This LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.
C. Linearity
A study was performed based on guidance from CLSI EP06-A. * This assay is linear across the analytical measuring interval of 3.5 to 5000.0 ng/L (3.5 to 5000.0 pg/mL).
D. Measuring Interval
Based on representative data for the LoQ, the ranges over which results can be quantified are provided below.
آ Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
11
| ng/L (pg/mL) | |
|---|---|
| AMIa | 3.5 - 5000.0 |
| Extended Measuring Interval (EMI)b | 5000.0 - 50,000.0 |
a AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ).
b EMI: The EMI extends from the ULoQ x dilution factor. The value reflects a 1:10 dilution factor.
E. Analytical Specificity
1. Interference
Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07-A2. * Each substance was tested at 2 levels of the analyte (approximately 15 ng/L and 500 ng/L). No significant interference (interference within ± 10%) was observed at the following concentrations:
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Unconjugated Bilirubin | ≤ 20 mg/dL |
| Conjugated Bilirubin | ≤ 20 mg/dL |
| Hemoglobin | ≤ 500 mg/dL |
| Total Protein | ≤ 9.3 g/dL |
| Triglycerides | ≤ 3000 mg/dL |
Interference beyond ± 10% was observed at the concentrations shown below for
the following substance.
| Potentially
Interfering
| Substance | Interferent Level | Analyte Level | % Interference |
|---|---|---|---|
| Total Protein | 12.4 g/dL | 15 ng/L | -12.0% |
| Total Protein | 12.4 g/dL | 500 ng/L | -18.4% |
§ Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition. CLSI Document EP07-A2. Wayne, PA: CLSI; 2005.
12
Total protein at 12.4 g/dL decreases troponin values at 15 ng/L and 500 ng/L by -12.0% and -18.4%, respectively.
Potentially Interfering Drugs
A study was performed based on guidance from CLSI EP07-A2. Each drug was tested at 2 levels of the analyte (approximately 15 ng/L and 500 ng/L). No significant interference (interference within ± 10%) was observed at the following concentrations:
| Potentially
Interfering Drug | Interferent Level | | Potentially
Interfering Drug | Interferent Level | |
|---------------------------------|-------------------|------------|---------------------------------|-------------------|-----------|
| | Therapeutic | High | | Therapeutic | High |
| Abciximab | 4 µg/mL | 20 µg/mL | Ibuprofen | 40 µg/mL | 500 µg/mL |
| Acetaminophen | 20 µg/mL | 250 µg/mL | Levodopa | 1.8 µg/mL | 20 µg/mL |
| Acetylsalicylic Acid | 260 µg/mL | 1000 µg/mL | Low MW Heparin | 1.8 U/mL | 5 U/mL |
| Adrenaline | 60 ng/mL | 0.37 µg/mL | Methyldopa | 4 µg/mL | 25 µg/mL |
| Allopurinol | 12 µg/mL | 400 µg/mL | Methylprednisolone | 8 µg/mL | 80 µg/mL |
| Ambroxol | 0.1 µg/mL | 400 µg/mL | Metronidazole | 23 µg/mL | 200 µg/mL |
| Ampicillin | 10 µg/mL | 1000 µg/mL | Nicotine | 37 ng/mL | 2 mg/dL |
| Ascorbic Acid | 12 µg/mL | 300 µg/mL | Nifedipine | 125 ng/mL | 60 µg/mL |
| Atenolol | 1 µg/mL | 10 µg/mL | Nitrofurantoin | 2.0 µg/mL | 64 µg/mL |
| Biotin | 10 ng/mL | 290 ng/mL | Nystatin | 2 µg/mL | 7.5 µg/mL |
| Bivalirudin | 11 µg/mL | 42 µg/mL | Oxytetracycline | 2 µg/mL | 5 µg/mL |
| Caffeine | 12 µg/mL | 100 µg/mL | Phenobarbital | 25 µg/mL | 15 mg/dL |
| Captopril | 1.0 µg/mL | 50 µg/mL | Phenylbutazone | 30 µg/mL | 400 µg/mL |
| Carvedilol | 5 µg/mL | 150 µg/mL | Phenytoin | 12 µg/mL | 100 µg/mL |
| Cefoxitin | 120 µg/mL | 2500 µg/mL | Primidone | 10 µg/mL | 10 mg/dL |
| Cinnarizine | 4 µg/mL | 400 µg/mL | Propranolol | 1 µg/mL | 5 µg/mL |
| Clopidogrel | 15 µg/mL | 75 µg/mL | Quinidine | 4 µg/mL | 20 µg/mL |
| Cocaine | 0.1 µg/mL | 10 µg/mL | Rifampicin | 7 µg/mL | 60 µg/mL |
| Cyclosporine | 0.8 µg/mL | 5 µg/mL | Salicylic Acid | 199 µg/mL | 600 µg/mL |
| Diclofenac | 2.5 µg/mL | 50 µg/mL | Simvastatin | 4 µg/mL | 20 µg/mL |
| Digoxin | 1 ng/mL | 7.5 µg/mL | Sodium Heparin | 2 U/mL | 8 U/mL |
| Dopamine | 0.3 µg/mL | 900 µg/mL | Streptokinase | 4 U/mL | 31.3 U/mL |
| Doxycycline | 10 µg/mL | 50 µg/mL | Theophylline | 12 µg/mL | 75 µg/mL |
| Eptifibatide | 2 µg/mL | 7 µg/mL | TPA | 0.52 µg/mL | 2.3 µg/mL |
| Erythromycin | 11 µg/mL | 200 µg/mL | Trimethoprim | 12 µg/mL | 75 µg/mL |
| Fibrinogen | 100 mg/dL | NA | Verapamil | 325 ng/mL | 160 µg/mL |
| Fondaparinux | 1.2 µg/mL | 4 µg/mL | Warfarin | 2 µg/mL | 30 µg/mL |
| Furosemide | 20 µg/mL | 400 µg/mL | | | |
MW = Molecular weight, NA = Not applicable, TPA = Tissue plasminogen activator
Interference beyond ± 10% was observed at the concentrations shown below for the following drug.
13
| Potentially Interfering
Substance | Interferent Level | | Analyte
Level | % Interference |
|--------------------------------------|-------------------|------------|------------------|----------------|
| Fibrinogen | NA | 1000 mg/dL | 15 ng/L | 11.6 |
Specimens from individuals with elevated levels of fibrinogen may demonstrate falsely elevated values.
Potentially Interfering Clinical Conditions
Twenty-three specimens positive for HAMA and 23 specimens positive for RF were evaluated for potential interference.
Specimens from patients who have received preparations of mouse monoclonal antibodies for diagnosis or therapy may contain HAMA. Such specimens may show either falsely elevated or depressed values when tested with assay kits such as ARCHITECT STAT High Sensitivity Troponin-I or others that employ mouse monoclonal antibodies. ** ** Specimens containing HAMA may show either falsely elevated or depressed values when tested with the ARCHITECT STAT High Sensitivity Troponin-I assay.
Heterophilic antibodies in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays. Patients routinely exposed to animals or to animal serum products can be prone to this interference, and anomalous values may be observed. Additional information may be required for diagnosis. **
RF in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays. * Specimens containing RF may show either falsely
Primus FJ, Kelley EA, Hansen HJ, et al. "Sandwich" type immunoassay of carcinoembryonic antigen in patients receiving murine monoclonal antibodies for diagnosis and therapy. Clin Chem 1988;34(2):261-264.
** Schroff RW, Foon KA, Beatty SM, et al. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1985;45(2):879-885.
Boscato LM, Stuart MC. Heterophilic antibodies: a problem for all immunoassays. Clin Chem 1988;34(1):27-33.
14
elevated or depressed values when tested with the ARCHITECT STAT High Sensitivity Troponin-I assay.
Although the ARCHITECT STAT High Sensitivity Troponin-I assay is specifically designed to minimize the effects of HAMA, heterophilic antibodies, and RF, assay results may be impacted by these proteins.
Troponin autoantibodies have been reported to be present in approximately 10% to 20% of patients presenting to the emergency department (ED) and may lead to falsely low troponin assay results and delay in treatment of acute coronary syndrome (ACS). §§ · *** Therefore, a test result that is inconsistent with the clinical picture and patient history should be interpreted with caution.
2. Cross-Reactants
A study was performed based on guidance from CLSI EP07-A2. Samples with cTnI concentrations from 3.5 to 5000 ng/L containing the cross-reactants listed in the following table were tested with the ARCHITECT STAT High Sensitivity Troponin-I assay.
The observed % cross-reactivity was 89 Park JY, Jaffe AS. Troponin autoantibodies: from assay interferent to mediator of cardiotoxicity. Clin Chem 2017;63(1):30-32.
*** Nussinovitch U, Shoenfeld Y. Anti-troponin autoantibodies and the cardiovascular system. Heart 2010;96:1518-1524.
15
F. Expected Values
A reference range study was conducted based on guidance from CLSI EP28-A 3c. *** Specimens were collected from 1531 apparently healthy individuals in a US population with normal levels of cardiac B-type natriuretic peptide (BNP) and HbA1c, and glomerular filtration rate (GFR) values ≥ 60 mL/min. Each specimen was stored frozen, thawed, and evaluated in replicates of one using the ARCHITECT STAT High Sensitivity Troponin-I assay. The 99th percentiles described in the following table for this population were determined using the robust statistical method described in CLSI EP28-A3c.
| Apparently Healthy
Population | N | Age Range
(years) | 99th Percentile
(ng/L, pg/mL) | 90% CI*
(ng/L, pg/mL) |
|----------------------------------|------|----------------------|----------------------------------|--------------------------|
| Female | 765 | 21 - 75 | 17 | [14, 20] |
| Male | 766 | 21 - 73 | 35 | [27, 44] |
| Overall | 1531 | 21 - 75 | 28 | [22, 33] |
- CI = Confidence Interval
IX. Summary of Clinical Performance
A multi-center prospective study was performed to assess diagnostic accuracy of the ARCHITECT STAT High Sensitivity Troponin-I assay. Specimens were collected at 11 EDs from 1065 subjects presenting to the ED with symptoms consistent with ACS. The specimen collection sites represented geographically diverse EDs associated with primary care hospitals and medical centers, reflecting regional, urban, suburban, and rural patient populations. All subject diagnoses were adjudicated by three board certified cardiologists according to the 2007 universal definition of MI *** before the ARCHITECT STAT High Sensitivity Troponin-I assay results were available. The final adjudicated diagnosis was made by majority agreement of the 3 board-certified cardiologists. The observed MI prevalence in this study was 10.89%.
#* Clinical and Laboratory Standards Institute (CLSI). Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline—Third Edition. CLSI Document EP28-A3c. Wayne, PA: CLSI; 2010.
Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur Heart J 2007;28(20):2525-2538.
16
- 248 specimens with serial sampling from 116 MI subjects (31 female subjects, . 85 male subjects)
- . 2488 specimens with serial sampling from 949 non-MI subjects (440 female subjects, 509 male subjects)
The specimens were collected in K2 EDTA tubes and frozen. The specimens were thawed and evaluated using the ARCHITECT STAT High Sensitivity Troponin-I assay.
NOTE: The study population did not include type 4 or 5 MI subjects. Therefore, the ability of the assay to identify these patients was not evaluated.
The results were analyzed using the serial sampling time points collected during the ED visit.
An analysis for both females and males was performed using the overall 99th percentile cutoff (28 ng/L). The results are summarized in the following table.
| Sex | Time
Pointa | Nb | Sensitivityc | | Specificityd | | PPVe | | NPVf | |
|--------|----------------|-----|-----------------|----------------|-------------------|----------------|------------------|----------------|-------------------|-----------------|
| | | | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI |
| Female | Baseline | 412 | 91.7
(22/24) | 73.0 -
99.0 | 92.0
(357/388) | 88.9 -
94.5 | 41.5
(22/53) | 28.1 -
55.9 | 99.4
(357/359) | 98.0 -
99.9 |
| | 2 - 4
Hours | 418 | 94.4
(17/18) | 72.7 -
99.9 | 89.3
(357/400) | 85.8 -
92.1 | 28.3
(17/60) | 17.5 -
41.4 | 99.7
(357/358) | 98.5 -
100.0 |
| | 4 - 9
Hours | 372 | 94.1
(16/17) | 71.3 -
99.9 | 87.0
(309/355) | 83.1 -
90.4 | 25.8
(16/62) | 15.5 -
38.5 | 99.7
(309/310) | 98.2 -
100.0 |
| Male | Baseline | 519 | 81.8
(54/66) | 70.4 -
90.2 | 81.5
(369/453) | 77.6 -
84.9 | 39.1
(54/138) | 30.9 -
47.8 | 96.9
(369/381) | 94.6 -
98.4 |
| | 2 - 4
Hours | 526 | 91.7
(55/60) | 81.6 -
97.2 | 83.5
(389/466) | 79.8 -
86.7 | 41.7
(55/132) | 33.2 -
50.6 | 98.7
(389/394) | 97.1 -
99.6 |
| | 4 - 9
Hours | 489 | 93.7
(59/63) | 84.5 -
98.2 | 81.0
(345/426) | 76.9 -
84.6 | 42.1
(59/140) | 33.9 -
50.8 | 98.9
(345/349) | 97.1 -
99.7 |
a All time points are relative to ED presentation / ED triage; baseline is within 2 hours of ED presentation / ED triage.
b Some time points could not be collected for some subjects.
For footnotes c-f:
| Diagnosis | |||
|---|---|---|---|
| ARCHITECT STAT High Sensitive Troponin-I | MI | Non-MI | |
| cTnI Value > cutpoint | A | B | |
| cTnI Value ≤ cutpoint | C | D |
c Sensitivity = A/(A + C) × 100
17
d Specificity = D/(B + D) × 100
- e Positive Predictive Value (PPV) = A/(A + B) × 100
- f Negative Predictive Value (NPV) = D/(C + D) × 100
The lower end of the CI for PPV demonstrated for female subjects using the established overall 99th percentile was as low as 15.5%. Taking into consideration the lower bound of the 95% CI, up to 71.9% (baseline), 82.5% (at 2 to 4 hours), and 84.5% (at 4 to 9 hours) of positive troponin results could come from females that are not having an MI.
The lower end of the CI for PPV demonstrated for male subjects using the established overall 99th percentiles was as low as 30.9%. Taking into consideration the lower bound of the 95% CI, up to 69.1% (baseline), 66.8% (at 2 to 4 hours), and 66.1% (at 4 to 9 hours) of positive troponin results could come from males that are not having an MI.
Troponin results should always be used in conjunction with clinical signs and symptoms in accordance with the fourth universal definition of MI§§§ requiring myocardial injury represented by a rise and/or fall of cTn values with at least one value above the 99th percentile URL and at least one of the following: symptoms of myocardial ischaemia, new ischaemic ECG changes, development of pathological O waves, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology, identification of a coronary thrombus by angiography or autopsy.
The results using the sex-specific 99th percentile cutoffs (female 17 ng/L, male 35 ng/L) are summarized in the following table.
§§§ Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018;72(18):2231-2264.
18
| Cutoff
(ng/L) | Time
Pointa | Nb | Sensitivityc | | Specificityd | | PPVe | | NPVf | |
|------------------------|----------------|-----|-----------------|-------------------------|-------------------|-------------------------|------------------|-------------------------|-------------------|--------------------------|
| | | | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI |
| 17
(Female
only) | Baseline | 412 | 95.8
(23/24) | 78.9 - 99.9 | 87.6
(340/388) | 83.9 - 90.7 | 32.4
(23/71) | 21.8 - 44.5 | 99.7
(340/341) | 98.4 - 100.0 |
| | 2 - 4
Hours | 418 | 94.4
(17/18) | 72.7 - 99.9 | 85.3
(341/400) | 81.4 - 88.6 | 22.4
(17/76) | 13.6 - 33.4 | 99.7
(341/342) | 98.4 - 100.0 |
| | 4 - 9
Hours | 372 | 94.1
(16/17) | 71.3 - 99.9 | 82.8
(294/355) | 78.5 - 86.6 | 20.8
(16/77) | 12.4 - 31.5 | 99.7
(294/295) | 98.1 - 100.0 |
| 35
(Male
only) | Baseline | 519 | 78.8
(52/66) | 67.0 - 87.9 | 84.5
(383/453) | 80.9 - 87.8 | 42.6
(52/122) | 33.7 - 51.9 | 96.5
(383/397) | 94.2 - 98.1 |
| | 2 - 4
Hours | 526 | 90.0
(54/60) | 79.5 - 96.2 | 86.1
(401/466) | 82.6 - 89.1 | 45.4
(54/119) | 36.2 - 54.8 | 98.5
(401/407) | 96.8 - 99.5 |
| | 4 - 9
Hours | 489 | 93.7
(59/63) | 84.5 - 98.2 | 84.3
(359/426) | 80.5 - 87.6 | 46.8
(59/126) | 37.9 - 55.9 | 98.9
(359/363) | 97.2 - 99.7 |
a All time points are relative to ED presentation / ED triage; baseline is within 2 hours of ED presentation / ED triage.
b Some time points could not be collected for some subjects.
For footnotes c-f:
| Diagnosis | ||
|---|---|---|
| ARCHITECT STAT High Sensitive Troponin-I | MI | Non-MI |
| cTnI Value > cutpoint | A | B |
| cTnI Value ≤ cutpoint | C | D |
c Sensitivity = A/(A + C) × 100
d Specificity = D/(B + D) × 100
e PPV = A/(A + B) × 100
t NPV = D/(C + D) × 100
The lower end of the CI for PPV demonstrated for female subjects using the established female 99th percentile was as low as 12.4%. Taking into consideration the lower bound of the 95% CI, up to 78.2% (baseline), 86.4% (at 2 to 4 hours), and 87.6% (at 4 to 9 hours) of positive troponin results could come from females that are not having an MI.
The lower end of the CI for PPV demonstrated for male subjects using the established male 99th percentile was as low as 33.7%. Taking into consideration the lower bound of the 95% CI, up to 66.3% (baseline), 63.8% (at 2 to 4 hours), and 62.1% (at 4 to 9 hours) of positive troponin results could come from males that are not having an MI.
Troponin results should always be used in conjunction with clinical signs and symptoms in accordance with the fourth universal definition of MI requiring myocardial injury
19
represented by a rise and/or fall of cTn values with at least one value above the 99th percentile URL and at least one of the following: symptoms of myocardial ischaemia, new ischaemic ECG changes, development of pathological Q waves, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology, identification of a coronary thrombus by angiography or autopsy.
There are conditions other than MI that are known to cause myocardial injury and elevated troponin values. The ARCHITECT STAT High Sensitivity Troponin-I clinical trial enrolled all patients presenting to the ED with symptoms consistent with ACS. Some of these patients had an acute or chronic condition other than MI.
In the clinical trial, 16.5% of patients without an MI diagnosis had at least one ARCHITECT STAT High Sensitivity Troponin-I test result above the sex-specific 99th percentile on one or more serial draws.
| Cardiac Conditions | Non-Cardiac Conditions |
|---|---|
| Angina | Cardiac contusion related to a traumatic injury |
| Atrial fibrillation | Chronic lung disease |
| Cardiomyopathy | Pneumonia |
| Coronary artery disease | Pulmonary embolism |
| Heart failure | Renal failure |
| Hypertensive urgency | Shock |
| Pericarditis | Systemic sclerosis |
| Recent cardiac intervention | |
| Severe valvular heart disease | |
| Tachycardia |
One or more of the following conditions were found in 71.3% of these patients:
The Area Under the Curve (AUC) results *** are summarized in the following table.
Obuchowski NA. Fundamentals of clinical research for radiologists: ROC analysis. Am J Roentgenol 2005;184(2):364-372.
20
| Sex | Time Pointa | Nb | AUC | Standard Error | 95% Wald CI |
|---|---|---|---|---|---|
| F | Baseline | 412 | 0.9458 | 0.0367 | [0.8738, 1.0000] |
| 2 - 4 Hours | 418 | 0.9402 | 0.0521 | [0.8381, 1.0000] | |
| 4 - 9 Hours | 372 | 0.9404 | 0.0544 | [0.8339, 1.0000] | |
| M | Baseline | 519 | 0.9136 | 0.0162 | [0.8818, 0.9453] |
| 2 - 4 Hours | 526 | 0.9388 | 0.0184 | [0.9028, 0.9747] | |
| 4 - 9 Hours | 489 | 0.9479 | 0.0191 | [0.9105, 0.9854] |
a All time points are relative to ED presentation / ED triage; baseline is within 2 hours of ED presentation / ED triage.
b Some time points could not be collected for some subjects.
X. Conclusion Drawn from Nonclinical Laboratory Studies and Clinical Performance
The results presented in this 510(k) premarket notification demonstrate that the candidate assay (ARCHITECT STAT High Sensitivity Troponin-I) performance is substantially equivalent to the predicate Elecsys Troponin T Gen 5 STAT Immunoassay (K162895).
The similarities and differences between the candidate assay and the predicate assay are presented in section VII. The results presented in this 510(k) provide reasonable assurance that the ARCHITECT STAT High Sensitivity Troponin-I assay is safe and effective for the stated intended use. Any differences between the candidate assay and the predicate assay shown in the tables do not affect the safety and effectiveness of the candidate assay.
There is no known potential adverse effect to the operator when using this in vitro device according to the ARCHITECT STAT High Sensitivity Troponin-I package insert instructions.