(80 days)
The Bayer ADVIA Chemistry Alpha-1-antitrypsin assay is an in vitro diagnostic device intended to quantitatively measure Alpha-1-antitrypsin concentration in human serum and plasma on the ADVIA® Chemistry system. Measurement of alpha-1-antitrypsin levels aid in the diagnosis of juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.
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Here's an analysis of the provided text, focusing on acceptance criteria and the study proving device performance:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds for performance metrics. Instead, it presents performance data for the new device alongside a predicate device (Roche) for comparison (for imprecision) and reports correlation with another comparison system (Hitachi) without direct acceptance values. The "acceptance" can be inferred by the FDA's clearance, which implies the device's performance was deemed substantially equivalent to a legally marketed predicate.
However, we can infer some criteria from the data provided:
| Performance Metric | Inferred Acceptance Criteria (Implicit) | Reported Device Performance (ADVIA 1650) | Comparison/Predicate Performance |
|---|---|---|---|
| Imprecision (CV%) | Similar or better within-run CV% compared to predicate, and generally low. | Level 91.83: 1.1% | Roche Level 67.5: 3.9% |
| Level 188.39: 0.83% | Roche Level 496.8: 0.7% | ||
| Level 346.99: 0.85% | Roche Level 574.8: 7.33% | ||
| Correlation ($R^2$) vs. a comparison system | Strong linear correlation (r value close to 1) | r = 0.965 | Not applicable (comparison system) |
| Interference (% Recovery) | % Recovery close to 100% (within a reasonable range, e.g., 90-110%) | Hemoglobin: 109.88% | Not applicable |
| Bilirubin conj: 102.83% | Not applicable | ||
| Bilirubin unconj: 98.84% | Not applicable | ||
| Intralipid: 109.05% | Not applicable | ||
| TRIG concentrate: 106.37% | Not applicable | ||
| Analytical Range | A suitable range for clinical diagnostic use. | 5.37 mg/dL to 510 mg/dL | Not applicable |
2. Sample Size Used for the Test Set and Data Provenance
- Imprecision: Not explicitly stated, but typically involves multiple replicates over several runs. The levels noted (e.g., 91.83 ug/dL) likely represent specific control or patient samples tested multiple times.
- Correlation:
- Sample Size: N = 44 (for serum specimens)
- Data Provenance: Not explicitly stated (e.g., country of origin). It is retrospective as these are existing samples being tested on two different systems.
- Interference: Not explicitly stated, but based on the table, 5 different interfering substances were tested. For each substance, it appears one AAT concentration was spiked with the interferent.
- Analytical Range: Not explicitly stated, but typically involves testing a series of diluted and concentrated samples to determine linearity.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of in vitro diagnostic device (IVD) for quantitative measurement of a biomarker does not rely on expert interpretation for ground truth in the same way an imaging AI or diagnostic algorithm might.
- For Imprecision, the "ground truth" is the established reference value of the control material or the sample's true concentration, measured meticulously in a laboratory setting.
- For Correlation, the "ground truth" for the comparison is the measurement obtained from the chosen comparison system (Hitachi AAT in this case).
- For Interference, the "ground truth" is the known concentration of alpha-1-antitrypsin in the sample before the interferent is added.
- For Analytical Range, the "ground truth" is the known concentration of standard solutions or diluted samples.
Therefore, the concept of "experts establishing ground truth" as it applies to diagnostic interpretation is not relevant here. The ground truth is inherent in the chemical and analytical properties of the samples and the established reference methods.
4. Adjudication Method for the Test Set
Not applicable. As explained above, this is a quantitative measurement, not a diagnostic interpretation that requires adjudication among experts.
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
Not applicable. This is an in vitro diagnostic assay (a laboratory test), not an AI-assisted diagnostic imaging or interpretation system that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented (imprecision, correlation, interference, analytical range) reflect the standalone performance of the device/method (Bayer ADVIA Chemistry Alpha-1-antitrypsin assay). This device is an automated chemical analyzer component, and its "performance" is its ability to accurately and precisely measure the analyte without human interpretive intervention.
7. The Type of Ground Truth Used
- For Imprecision: Reference material values or meticulously measured sample concentrations.
- For Correlation: Measurements from a predicate/comparison device (Hitachi AAT).
- For Interference: Known spiked concentrations and baseline measurements of the unspiked sample.
- For Analytical Range: Gravimetrically or volumetrically prepared standard solutions.
8. The Sample Size for the Training Set
Not applicable in the context of an IVD assay's analytical validation. This device is not an AI/ML model that requires a distinct "training set." The development of the assay (e.g., reagent formulation, assay parameters) would involve extensive R&D and optimization, but not a "training set" in the machine learning sense. The data presented are for verification and validation of the final assay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there's no "training set" in the AI/ML context for this type of device. The accuracy of the assay itself is validated against established analytical principles and reference methods.
§ 866.5130
Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition,alpha -1-antitrypsin deficiency has been associated with pulmonary emphysema.(b)
Classification. Class II (performance standards).