(195 days)
The Barbiturates assay is used for the qualitative analysis of barbiturates in human urine with a cutoff of 200 ng/mL for use in clinical laboratories. Measurements obtained by this device are used in the diagnosis and treatment of barbiturates use or overdose. The Barbiturates assay is calibrated with secobarbital and will detect a variety of Barbiturates. The Barbiturates assay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
Barbiturates is an in vitro diagnostic assay for the qualitative analysis of barbiturates in human urine. The assay is a homogeneous enzyme immunoassay with a 200 ng/mL cutoff. The assay is based on competition between drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts NAD to NADH, resulting in an absorbance change that can be measured spectrophotometrically.
Here's an analysis of the provided text, focusing on the acceptance criteria and study information for the Barbiturates assay:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to a predicate device and GC/MS, rather than explicitly stated as numerical targets. The overall goal is "acceptable correlation" and "substantial equivalence."
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Substantial equivalence to predicate device (Emit® II Barbiturate assay on SYVA®-30R) for qualitative analysis. | Concordance with Predicate Device (Emit® II Barbiturate assay): 96% agreement. Six samples were negative by Emit II but positive by the Barbiturates assay; these were confirmed by GC/MS to contain phenobarbital between 661 and 1,048 ng/mL (well above the 200 ng/mL cutoff). This suggests the new assay might be more sensitive or detecting a broader range of barbiturates, aligning with "acceptable correlation." |
| Acceptable correlation with GC/MS (confirmatory method) | Concordance with GC/MS: 100% agreement. (This is stated after mentioning the 6 samples confirmed by GC/MS, implying that when GC/MS was used as the reference, the Barbiturates assay matched). |
| Acceptable precision | Precision Studies (Total %CV): |
| - Verifier I: 0.47% | |
| - Cutoff Calibrator: 0.53% | |
| - Verifier II: 0.55% | |
| -25% Control of Cutoff Calibrator: 0.61% | |
| +25% Control of Cutoff Calibrator: 0.55% | |
| Limit of Detection (Sensitivity) | 20 ng/mL |
| Device cutoff for qualitative analysis (200 ng/mL) | Barbiturates assay cutoff: 200 ng/mL (Matches the intended use and predicate device's cutoff for qualitative analysis, which is implied as similar to the new device's qualitative nature). |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set): The document doesn't explicitly state the total number of samples used for the comparative performance studies. It mentions that "Six samples were negative using the Emit II Barbiturate assay on the SYVA-30R Analyzer and positive using the Barbiturates assay," and then were confirmed by GC/MS. It also states "The clinical specimens tested ranged from 302 to 6,481 ng/mL." This suggests a set of clinical specimens was used, but the exact number isn't provided.
- Data Provenance: Not specified. It's unclear if the data is prospective or retrospective, or the country of origin.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not applicable/not mentioned. The ground truth for the comparison studies was established using a predicate device (Emit II Barbiturate assay) and Gas Chromatography/Mass Spectrometry (GC/MS), which is an analytical chemical method, not human expert interpretation.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The "adjudication" was primarily through comparison to a well-established predicate laboratory device and a gold standard analytical method (GC/MS). If there were discrepancies between the new assay and the predicate, GC/MS was used as the definitive adjudicator (as seen with the 6 samples mentioned).
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
- MRMC Study: No, an MRMC study was not done. This device is an in vitro diagnostic assay (laboratory test), not an AI-powered image analysis or diagnostic support tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Standalone Performance: Yes, the entire study focuses on the standalone performance of the Barbiturates assay (an IVD kit) as evaluated on the AEROSET® System. It assesses the assay's performance characteristics (concordance, precision, sensitivity) independently.
7. The Type of Ground Truth Used
- Type of Ground Truth:
- Predicate Device Performance: Comparison to the Emit® II Barbiturate assay on the SYVA®-30R Analyzer served as a primary reference point for establishing "substantial equivalence."
- Gas Chromatography/Mass Spectrometry (GC/MS): This was used as the definitive "gold standard" confirmatory method, especially for resolving discrepancies between the new assay and the predicate (e.g., the 6 discrepant samples). GC/MS is an objective analytical method.
8. The Sample Size for the Training Set
- Sample Size (Training Set): Not specified. For IVD assays, "training sets" are usually not applicable in the same way they are for AI/ML. The assay is developed based on chemical/biological principles and calibrated, not "trained" on data to learn patterns. The calibration process implicitly uses specific samples (e.g., the 200 ng/mL cutoff calibrator), but a "training set" size for algorithm development isn't relevant here.
9. How the Ground Truth for the Training Set Was Established
- Ground Truth (Training Set): Not applicable in the context of an IVD assay's "training set." The assay's fundamental chemistry and cutoff (200 ng/mL, calibrated with secobarbital) are established through analytical chemistry and toxicology principles, not a data-driven "ground truth" as in machine learning model training.
§ 862.3150 Barbiturate test system.
(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).