(90 days)
The Atellica® IM High-Sensitivity Troponin I (TnIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin) using the Atellica® IM Analyzer. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
The Atellica IM TnIH assay can be used as an aid in prognosis for 30-, 182-, and 365-day all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS). MACE consists of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization.
The Atellica® IM TnIH assay is a 3-site sandwich immunoassay using direct chemiluminescent technology. The Solid Phase reagent consists of magnetic particles conjugated with streptavidin with 2 bound biotinylated capture monoclonal antibodies, each recognizing a unique cTnl epitope.
The Lite Reagent comprises a conjugate with an architecture consisting of a proprietary acridinium ester and a recombinant anti-human cTnl sheep Fab covalently attached to bovine serum albumin (BSA) for chemiluminescent detection.
A direct relationship exists between the amount of cTnl present in the patient sample and the amount of relative light units (RLUs) detected by the system.
The provided document is a 510(k) summary for the Atellica® IM High-Sensitivity Troponin I (TnIH) assay, detailing its substantial equivalence to a predicate device and supporting the addition of a prognostic indication for use. However, it does not explicitly define acceptance criteria as a separate, quantitative table with pass/fail metrics. Instead, the "Performance Characteristics – Clinical Study" section presents the study objective and results that demonstrate the device's performance for the new prognostic indication, implicitly serving as the validation for meeting the FDA's requirements for substantial equivalence.
Based on the information provided, here's a breakdown of the requested elements:
1. A table of acceptance criteria and the reported device performance
The document does not provide a formal table of acceptance criteria with quantitative thresholds for "pass/fail". The study's objective was to demonstrate the ability of the device to predict future mortality or adverse cardiac events. The reported performance focuses on:
- Hazard Ratios (Unadjusted and Adjusted): Showing the increased risk of ACM/MACE for patients with cTnI levels >99th percentile compared to those ≤99th percentile.
- Post-test risk: The cumulative incidence of ACM/MACE for the two troponin level groups.
- Kaplan-Meier Curves: Visually representing the absolute risk of events over time for the two groups.
The implicit acceptance criteria for this prognostic indication would be that the device's measurements (specifically, cTnI levels > 99th percentile) demonstrate a statistically significant association with increased future risk of all-cause mortality (ACM) and major adverse cardiac events (MACE) across the specified follow-up periods (30, 90, 182, and 365 days) in the relevant patient populations.
Reported Device Performance (Excerpted from the document, focusing on statistically significant findings):
| Metric / Population | Follow-Up Time Point | cTnI Levels | Number of Patients (N) / Events (Events) | Post-test risk of ACM/MACE (%, 95% CI) | Unadjusted Hazard Ratio (95% CI) | Adjusted Hazard Ratio (95% CI) |
|---|---|---|---|---|---|---|
| Population 3 (Includes history of MACE) | 90 Days | >99th Percentile | N=137, Events=36 | 26.3 (20.4, 33.2) | 2.24 (1.52, 3.29) | 1.61 (1.06, 2.45) |
| 182 Days | >99th Percentile | N=137, Events=49 | 35.8 (29.0, 43.2) | 2.09 (1.51, 2.90) | 1.59 (1.12, 2.26) | |
| 365 Days | >99th Percentile | N=137, Events=67 | 48.9 (41.4, 56.4) | 2.21 (1.67, 2.92) | 1.56 (1.15, 2.12) | |
| Population 2, Lithium Heparin Plasma (Excludes AMI & prior MACE) | 30 Days | >99th Percentile | N=53, Events=3 | 5.7 (2.2, 13.6) | 10.89 (2.72, 43.53) | 7.46 (1.65, 33.65) |
| 90 Days | >99th Percentile | N=53, Events=4 | 7.5 (3.2, 16.7) | 6.84 (2.23, 20.98) | 5.58 (1.69, 18.47) | |
| 182 Days | >99th Percentile | N=53, Events=7 | 13.2 (6.9, 23.9) | 5.28 (2.32, 12.02) | 3.89 (1.63, 9.30) | |
| 365 Days | >99th Percentile | N=53, Events=8 | 15.1 (8.1, 26.4) | 3.69 (1.75, 7.79) | 2.79 (1.28, 6.08) | |
| Population 2, Serum (Excludes AMI & prior MACE) | 30 Days | >99th Percentile | N=57, Events=2 | 3.5 (1.0, 11.4) | 5.08 (1.08, 23.94) | 2.84 (0.56, 14.38) |
| 90 Days | >99th Percentile | N=57, Events=3 | 5.3 (1.9, 13.9) | 3.87 (1.13, 13.28) | 2.81 (0.78, 10.12) | |
| 182 Days | >99th Percentile | N=57, Events=6 | 10.5 (5.1, 20.5) | 3.80 (1.59, 9.07) | 2.71 (1.10, 6.69) | |
| 365 Days | >99th Percentile | N=57, Events=7 | 12.3 (6.2, 22.8) | 2.75 (1.25, 6.05) | 2.06 (0.92, 4.64) | |
| Population 1 (Excludes adjudicated AMI) | 90 Days | >99th Percentile | N=190, Events=40 | 21.1 (16.4, 26.6) | 4.03 (2.80, 5.80) | 2.03 (1.36, 3.01) |
| 182 Days | >99th Percentile | N=190, Events=56 | 29.5 (24.0, 35.6) | 3.66 (2.71, 4.95) | 1.97 (1.42, 2.73) | |
| 365 Days | >99th Percentile | N=190, Events=75 | 39.5 (33.3, 46.0) | 3.64 (2.81, 4.72) | 1.85 (1.39, 2.47) |
Note: Bolded Hazard Ratios indicate statistically significant findings (95% CI does not cross 1.0). Italicized Hazard Ratios (e.g., serum at 30, 90, 365 days for Population 2) are explicitly marked as "Not Statistically Significant" in the document.
The overall conclusion states: "The results of the clinical study provided in this submission support the addition of an indication for use as an aid in prognosis for all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS)." This implies that the observed effects (higher risk for cTnI > 99th percentile) were deemed sufficient, particularly for the statistically significant findings.
2. Sample sized used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Test Set Sample Size:
- Population 1: 2064 patients
- Population 2:
- Lithium Heparin Plasma: 1190 patients
- Serum: 1214 patients
- Population 3: 874 patients
- Data Provenance: The document states, "This prognostic risk analysis utilized the same emergency department cohort previously described in K171566." It does not explicitly state the country of origin. The study was prospective in terms of follow-up for outcomes after initial presentation, as patients were "followed up for 30-, 90-, 182-, and 365-day progression to ACM and MACE."
3. 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)
The ground truth for Adjudicated AMI was mentioned ("Entire Population Excluding Subjects with Adjudicated AMI"). The document does not specify the number or qualifications of experts used for establishing this adjudication or for the MACE/ACM outcomes. It says "a detailed symptom history was obtained for each subject" and "the following information was collected from each subject's medical chart." This suggests medical record review, but the specific adjudicators are not detailed.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
The document mentions "adjudicated AMI" and the collection of outcome data (ACM/MACE events). However, it does not describe the specific adjudication method (e.g., how many reviewers, conflict resolution) for AMI or the MACE/ACM outcomes. It implies that MACE consisted of clearly defined clinical events (myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization) which are typically obtained from medical records.
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. This is an in vitro diagnostic (IVD) assay for measuring a biomarker (Troponin I). It is not an AI-assisted imaging device or a device involving "human readers" in the typical sense of an MRMC study. The study assesses the prognostic performance of the cTnI assay result itself, not human interpretation enhanced by AI.
6. If a standalone (i.e., algorithm only without human-in-the loop performance) was done
Yes, in a sense. The performance evaluated is that of the assay (the Atellica® IM High-Sensitivity Troponin I (TnIH) measurement) as a standalone prognostic indicator, reported as a quantitative value. It's the "algorithm" of the assay (producing the cTnI value) that is assessed for its ability to predict outcomes in patient populations, without direct human cognitive input being part of the primary performance metric. Clinical decision-making would then incorporate this result.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the prognostic indication was outcomes data, specifically:
- All-Cause Mortality (ACM)
- Major Adverse Cardiac Events (MACE): Consisting of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization.
This long-term outcome data was collected from patient follow-up over 30, 90, 182, and 365 days.
8. The sample size for the training set
The document describes a clinical performance study for the new prognostic indication. It does not mention a separate "training set" for model development, implying that this was a single-cohort validation study using the full collected dataset (the test set described above). The purpose of the submission is to expand the intended use of an already existing device (cleared under K171566), suggesting the core assay technology was already established.
9. How the ground truth for the training set was established
As no separate "training set" is explicitly mentioned for the prognostic model development (if one occurred), this question is not fully answerable from the provided text. The ground truth for the clinical validation (the "test set") was established through prospective follow-up for clinical outcomes (ACM/MACE) as described in point 7.
§ 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.