(122 days)
The Bayer ADVIA IMS Acetaminophen method is an in vitro diagnostic device intended to measure acctaminophen levels in human serum or plasma (Lithium heparin). Such measurements are used in the diagnosis of acetaminophen toxicity and overdose.
This in-vitro diagnostic method is intended to measure acetaminophen in human serum and plasma using lithium heparin as the anticoagulant on ADVIA® IMS™. Acetaminophen (Tylenol, paracetamol, p-hydroxyacetanilide) is used in many formulations as an analgesic, generally with no adverse effects. Measurement of acetaminophen is used in the diagnosis and treatment of severe liver damage caused by overdose through chronic usage, accident or self-infliction.
Here's an analysis of the provided text to extract the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a formal, enumerated list. However, based on the performance data presented and the conclusion of equivalence to a predicate device, we can infer the implied acceptance criteria were met by showing comparable or better performance in the following areas:
| Criteria Category | Implied Acceptance Criterion | Reported Device Performance (ADVIA IMS) |
|---|---|---|
| Imprecision (CV%) | CV% should be comparable to or better than the predicate device (Abbott/TDx) at similar levels. | |
| Level 1.5 mg/dL | ≤ 4.9% (Predicate device value) | 2.6% |
| Level 5.0 mg/dL (approx) | ≤ 3.0% (Predicate device 3.5 mg/dL) | 1.5% |
| Level 14.9-15 mg/dL | ≤ 3.9% (Predicate device 15 mg/dL) | 1.3% |
| Correlation (Regression) | Strong correlation with the predicate device (Y=ADVIA IMS, X=comparison system) with an R-value close to 1 and a regression equation close to Y=X. | |
| Serum (vs Abbott/TDx) | R-value close to 1, slope close to 1, intercept close to 0. | R=0.999, Y=1.05X - 0.25 |
| Plasma (y) vs Serum (x) (within ADVIA IMS) | R-value close to 1, slope close to 1, intercept close to 0. | R=0.998, Y=1.00X + 0.05 |
| Correlation (Syx) | Syx (standard error of the estimate) should be low, indicating good agreement. | |
| Serum (vs Abbott/TDx) | Low value (e.g., -15% | -4% |
| Lipids (Triglycerides) | >-15% | -9% |
| Analytical Range | Sufficient range for clinical use (0-20 mg/dL). | 0 to 20 mg/dL |
2. Sample Sizes and Data Provenance
- Test Set Sample Sizes:
- Imprecision (Serum): Not explicitly stated how many samples per level were used for CV calculation, but generally, this involves replicate measurements on multiple samples.
- Correlation (Serum vs Abbott/TDx): 46 specimens
- Correlation (Plasma vs Serum on ADVIA IMS): 50 specimens
- Interfering Substances: A single Acetaminophen concentration was tested for each interferent, but the number of unique samples is not specified.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It implies the studies were conducted by Bayer Corporation for regulatory submission.
3. Number of Experts and Qualifications for Ground Truth
This type of in-vitro diagnostic device (an assay for a chemical compound) typically does not rely on human experts to establish "ground truth" for the test set in the same way imaging devices do. The ground truth for such assays is established through:
- Reference Methods: Highly accurate and precise analytical methods (e.g., GC-MS, HPLC) or certified reference materials are used to assign true values to samples.
- Predicate Device Measurements: For comparison studies, the predicate device itself serves as a "ground truth" for the new device, assuming the predicate device is already validated and accepted.
The document does not mention any human experts or their qualifications for establishing ground truth.
4. Adjudication Method for the Test Set
Not applicable. As described in point 3, this device's performance evaluation does not involve subjective interpretations requiring adjudication by experts. The ground truth for quantitative assays is based on analytical measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is an in-vitro diagnostic assay for measuring acetaminophen concentrations, not an imaging device or a device requiring human interpretation of results in a diagnostic imaging workflow. Therefore, an MRMC study is not relevant or performed for this type of device.
6. Standalone Performance
Yes, the studies presented (Imprecision, Correlation, Interfering Substances, Analytical Range) represent the standalone performance of the ADVIA IMS Acetaminophen method. The "Correlation" section specifically compares the new device's measurements (Y) against a known comparison system (X), which serves as a benchmark for its standalone accuracy.
7. Type of Ground Truth Used
The ground truth used for this device's evaluation is primarily comparison to a legally marketed predicate device (Abbott/TDx) and likely reference methods or certified materials for establishing the validity of the predicate device and the new device's calibration and analytical range. For the interference study, the "true" acetaminophen concentration would have been precisely known when the interfering substance was added.
8. Sample Size for the Training Set
The document does not provide information about a "training set" or its sample size. For an in-vitro diagnostic assay of this nature, the development process typically involves:
- Method development and optimization.
- Calibration using a set of calibrators (the calibrator part number 04919015 is mentioned).
- Verification and validation studies using various types of samples to assess precision, accuracy, linearity, interference, etc.
There typically isn't a "training set" in the machine learning sense, as this is a chemical assay, not an AI/ML algorithm.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no mention of a "training set" in the context of an AI/ML algorithm. The calibration process for the assay would establish its measurement curve, and this would be based on precisely known concentrations of acetaminophen.
§ 862.3030 Acetaminophen test system.
(a)
Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of acetaminophen overdose.(b)
Classification. Class II.