(184 days)
The Propoxyphene assay is used for the qualitative analysis of propoxyphene in human urine with a cutoff of 300 ng/mL for used a clinical laboratories. Measurements obtained by this device are used in the diagnosis and treatment of propoxyphene use or overdose. The Propoxyphene assay is calibrated with propoxyphene and will detect propoxyphene and metabolites and analogs. The Propoxyphene assay provides only a preliminary analytical test result. A more specific alternate chemical method must be 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 results are used.
Propoxyphene is an in vitro diagnostic assay for the qualitative analysis of Propoxyphene in human urine. The assay is a homogeneous enzyme, immunoassay with a 300 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.
The provided text describes the Propoxyphene assay, an in vitro diagnostic assay for the qualitative analysis of Propoxyphene in human urine. The study conducted aims to demonstrate its substantial equivalence to the Emit® II Propoxyphene assay (K923873).
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for the Propoxyphene assay in a tabular format with numerical targets. Instead, it defines the performance characteristics and demonstrates substantial equivalence to a predicate device. The primary performance metric reported is concordance (agreement) with the predicate device.
| Acceptance Criteria (Implied) | Reported Device Performance (Propoxyphene assay) |
|---|---|
| Substantial equivalence to Emit® II Propoxyphene assay | Concordance with Emit® II Propoxyphene assay: 99% agreement |
| Acceptable correlation with Emit® II Propoxyphene assay | "Acceptable correlation" |
| Agreement with GC/MS (confirmatory method) | "Agreement with GC/MS" |
| Precision (for Verifier I, Cutoff Calibrator, Verifier II, ±25% Controls) | Total %CV for Verifier I: 1.25% |
| Total %CV for Cutoff Calibrator: 1.49% | |
| Total %CV for Verifier II: 1.19% | |
| Total %CV for -25% Control of Cutoff Calibrator: 2.39% | |
| Total %CV for +25% Control of Cutoff Calibrator: 1.90% | |
| Cutoff concentration | 300 ng/mL |
| Limit of Detection (Sensitivity) | 60 ng/mL |
Note on "Acceptance Criteria": For substantial equivalence claims, the acceptance criteria are often implicitly tied to demonstrating that the new device performs "as well as" or "similarly to" the predicate device for its intended use. Here, 99% agreement with the predicate device appears to be the key performance indicator used to support substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: Not explicitly stated as a single number for the comparative performance study. The text mentions "The clinical specimens tested ranged from 404 to 56,662 ng/mL," implying that multiple clinical specimens were used. However, the exact number tested for the 99% concordance is not provided.
- Data Provenance: Not specified (e.g., country of origin). The study used "clinical specimens." It is not stated whether the data was retrospective or prospective, but clinical specimens usually imply retrospective collection for such comparative studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not applicable. For this type of in vitro diagnostic assay, the "ground truth" for the test set is established by a reference method, not by human experts.
- Qualifications of Experts: N/A.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The ground truth is established by a reference method (GC/MS for confirmatory analysis, and the predicate device for comparative performance), not by a consensus of experts. Discrepancies between the new device and the predicate device were resolved by GC/MS (e.g., the one discordant sample was confirmed by GC/MS).
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, this is an in vitro diagnostic device for analyte detection, not an imaging analysis or decision support system that involves human readers interpreting cases. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study is not relevant here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Standalone Performance: Yes, the device's performance characteristics (e.g., concordance, precision, cutoff, limit of detection) are reported for the instrument-based assay itself, operating without human interpretation of the primary result. The assay generates a qualitative result (positive/negative) based on spectrophotometric measurements. The phrase "qualitative analysis" refers to the output of the device.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- Type of Ground Truth:
- For the comparative study assessing agreement, the Emit® II Propoxyphene assay (predicate device) was used as a reference for initial comparison.
- For resolving discrepancies and confirming concentrations, GC/MS (Gas Chromatography/Mass Spectrometry) was used, which is considered the "gold standard" confirmatory method for drug testing.
8. The Sample Size for the Training Set
- Sample Size for Training Set: Not applicable/not provided. This document describes the performance of a developed assay for regulatory submission, not the development process involving a separate training set for a machine learning model. Immunoassays are not "trained" in the machine learning sense; rather, they are designed and optimized based on chemical and biological principles.
9. How the Ground Truth for the Training Set was Established
- Ground Truth for Training Set: Not applicable. As mentioned above, this is an immunoassay, not a machine learning model, so there isn't a "training set" with ground truth in the AI context. The assay's parameters would have been optimized through laboratory experimentation and validation, rather than learning from a labeled training dataset.
§ 862.3700 Propoxyphene test system.
(a)
Identification. A propoxyphene test system is a device intended to measure propoxyphene, a pain-relieving drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of propoxyphene use or overdose or in monitoring levels of propoxyphene to ensure appropriate therapy.(b)
Classification. Class II (special controls). A propoxyphene 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).