(88 days)
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).
The ARCHITECT STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of cardiac troponin I (cTnI) in human plasma (dipotassium EDTA) using chemiluminescent microparticle immunoassay technology with flexible assay protocols, referred to as Chemiflex. The reagent kit contains anti-troponin I (mouse, monoclonal) coated microparticles and anti-troponin I (mouse-human chimeric, monoclonal) acridinium-labeled conjugate. The procedure involves combining sample and antibody-coated microparticles, incubation and wash, adding acridinium-labeled conjugate, another wash cycle, and then adding Pre-Trigger and Trigger Solutions. The resulting chemiluminescent reaction is measured as relative light units (RLUs), which are directly related to the amount of cTnI in the sample. The cTnI concentration is determined relative to a standard curve.
The provided text describes the Abbott Laboratories ARCHITECT STAT High Sensitivity Troponin-I assay (K191595). Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a numerical or categorical format for diagnostic performance (e.g., "Sensitivity must be >X%"). Instead, it presents the performance characteristics observed in the clinical study, implying that these demonstrated values were deemed acceptable for substantial equivalence. The non-clinical performance (precision, linearity, limits of measurement, and analytical specificity) results are presented as the device performance and are implicitly accepted as demonstrating substantial equivalence to the predicate.
For the purpose of this response, I will consider the reported "Sensitivity" and "Specificity" values at different time points and cutoffs as the "reported device performance." The document states that the conclusion drawn from nonclinical laboratory studies and clinical performance is 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). This implies the presented performance metrics met the FDA's criteria for substantial equivalence.
Reported Device Performance (Clinical Study - Myocardial Infarction Diagnosis):
| Metric | Sex | Time Point | Cutoff (ng/L) | Reported Performance (%) | 95% CI (%) |
|---|---|---|---|---|---|
| Sensitivity | Female | Baseline | 28 (Overall) | 91.7 | 73.0 - 99.0 |
| Female | 2 - 4 Hours | 28 (Overall) | 94.4 | 72.7 - 99.9 | |
| Female | 4 - 9 Hours | 28 (Overall) | 94.1 | 71.3 - 99.9 | |
| Male | Baseline | 28 (Overall) | 81.8 | 70.4 - 90.2 | |
| Male | 2 - 4 Hours | 28 (Overall) | 91.7 | 81.6 - 97.2 | |
| Male | 4 - 9 Hours | 28 (Overall) | 93.7 | 84.5 - 98.2 | |
| Female | Baseline | 17 (Female) | 95.8 | 78.9 - 99.9 | |
| Female | 2 - 4 Hours | 17 (Female) | 94.4 | 72.7 - 99.9 | |
| Female | 4 - 9 Hours | 17 (Female) | 94.1 | 71.3 - 99.9 | |
| Male | Baseline | 35 (Male) | 78.8 | 67.0 - 87.9 | |
| Male | 2 - 4 Hours | 35 (Male) | 90.0 | 79.5 - 96.2 | |
| Male | 4 - 9 Hours | 35 (Male) | 93.7 | 84.5 - 98.2 | |
| Specificity | Female | Baseline | 28 (Overall) | 92.0 | 88.9 - 94.5 |
| Female | 2 - 4 Hours | 28 (Overall) | 89.3 | 85.8 - 92.1 | |
| Female | 4 - 9 Hours | 28 (Overall) | 87.0 | 83.1 - 90.4 | |
| Male | Baseline | 28 (Overall) | 81.5 | 77.6 - 84.9 | |
| Male | 2 - 4 Hours | 28 (Overall) | 83.5 | 79.8 - 86.7 | |
| Male | 4 - 9 Hours | 28 (Overall) | 81.0 | 76.9 - 84.6 | |
| Female | Baseline | 17 (Female) | 87.6 | 83.9 - 90.7 | |
| Female | 2 - 4 Hours | 17 (Female) | 85.3 | 81.4 - 88.6 | |
| Female | 4 - 9 Hours | 17 (Female) | 82.8 | 78.5 - 86.6 | |
| Male | Baseline | 35 (Male) | 84.5 | 80.9 - 87.8 | |
| Male | 2 - 4 Hours | 35 (Male) | 86.1 | 82.6 - 89.1 | |
| Male | 4 - 9 Hours | 35 (Male) | 84.3 | 80.5 - 87.6 | |
| AUC | Female | Baseline | N/A | 0.9458 | 0.8738-1.0000 |
| Female | 2 - 4 Hours | N/A | 0.9402 | 0.8381-1.0000 | |
| Female | 4 - 9 Hours | N/A | 0.9404 | 0.8339-1.0000 | |
| Male | Baseline | N/A | 0.9136 | 0.8818-0.9453 | |
| Male | 2 - 4 Hours | N/A | 0.9388 | 0.9028-0.9747 | |
| Male | 4 - 9 Hours | N/A | 0.9479 | 0.9105-0.9854 |
2. Sample size used for the test set and the data provenance
-
Test Set Sample Size:
- Clinical Study: 1065 subjects presenting to the ED with symptoms consistent with ACS.
- 248 specimens with serial sampling from 116 MI subjects (31 female, 85 male).
- 2488 specimens with serial sampling from 949 non-MI subjects (440 female, 509 male).
- Reference Range Study: 1531 apparently healthy individuals.
- Clinical Study: 1065 subjects presenting to the ED with symptoms consistent with ACS.
-
Data Provenance:
- Clinical Study: Multi-center prospective study from 11 geographically diverse EDs in the US.
- Reference Range Study: US population.
- The document implies the studies are prospective as subjects were enrolled for acute clinical presentation (ACS symptoms) and for reference range establishment. Specimens were collected and frozen for subsequent evaluation.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Number of Experts: Three.
- Qualifications of Experts: Board-certified cardiologists.
4. Adjudication method for the test set
- Adjudication Method: The final adjudicated diagnosis (ground truth) was made by majority agreement of the three board-certified cardiologists. This is often referred to as a 3+1 method where consensus among the human readers determines the outcome.
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, a multi-reader multi-case (MRMC) comparative effectiveness study concerning human readers improving with or without AI assistance was not done. This device is an in vitro diagnostic (IVD) assay, a laboratory test system, not an AI or imaging diagnostic software that assists human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the clinical study assessed the standalone performance of the ARCHITECT STAT High Sensitivity Troponin-I assay. The assay itself provides a quantitative measurement and these measurements, when compared against the adjudicated clinical diagnosis, determine its diagnostic accuracy (sensitivity, specificity, etc.). There is no "human-in-the-loop" explicitly described for interpreting the assay result itself, although clinicians use the results in conjunction with other clinical signs.
7. The type of ground truth used
- Clinical Study: The ground truth for the diagnosis of myocardial infarction (MI) was established by the adjudicated diagnosis of three board-certified cardiologists according to the 2007 universal definition of MI. The document also states that troponin results should always be used in conjunction with clinical signs and symptoms in accordance with the fourth universal definition of MI.
- Reference Range Study: Ground truth for "apparently healthy individuals" was based on participants having normal levels of cardiac B-type natriuretic peptide (BNP) and HbA1c, and glomerular filtration rate (GFR) values ≥ 60 mL/min.
8. The sample size for the training set
The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is an immunoassay (hardware and reagents), not an AI algorithm. Therefore, the concept of a "training set" as it relates to AI is not applicable here. The focus is on the analytical and clinical validation of the assay.
9. How the ground truth for the training set was established
As noted above, the concept of a "training set" as related to AI is not applicable to this device submission.
§ 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.