(69 days)
The Emit® II Plus Propoxyphene Assay is a homogeneous drugs-of-abuse enzyme immunoassay with a 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of propoxyphene in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The Emit® II Plus Propoxyphene Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
The Syva Emit® II Plus Propoxyphene Assay is a homogenous enzyme assay intended for use in qualitative and semiquantitative analysis of propoxyphene in urine.
The provided text describes the Syva Emit® II Plus Propoxyphene Assay, a homogeneous enzyme immunoassay for the qualitative and semiquantitative analysis of propoxyphene in human urine. The submission is a 510(k) for substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Comparative Analysis | Equivalent to the predicate device (Syva Emit® II Propoxyphene Assay) with regard to intended use, assay sample, and overall performance characteristics. High agreement in finding samples negative and positive compared to the predicate method. | "The Syva Emit® II Plus Propoxyphene Assay showed excellent correlation to the predicate method. The comparative analysis to the predicate method resulted in 98% agreement in finding samples negative and positive." |
| Spiked Sample Recovery (Qualitative) | Consistently distinguish negative and positive samples around the 300 ng/mL cutoff: |
- Spiked at ≤ -25% of cutoff (0 to 225 ng/mL) should be consistently negative.
- Spiked at ≥ +25% of cutoff (375 to 1500 ng/mL) should be consistently positive. | "In qualitative spike analysis, the Emit® II Plus Propoxyphene Assay using a 300 ng/mL cutoff correctly identified the spiked specimens as being negative and positive. Known levels of propoxyphene, spiked at levels less than or equal to minus 25% of the cutoff (0 to 225 ng/mL) were consistently distinguished as negative and those spiked at levels greater than or equal to plus 25% of the cutoff (375 to 1500 ng/mL) were consistently distinguished as positive." |
| Spiked Sample Recovery (Semiquantitative Accuracy) | For known concentrations within the semiquantitative range (75 to 450 ng/mL), drug recovery should be accurate, with a specified margin of error. | "Within this range [75 to 450 ng/mL], recovery ranged up to ± 13% of nominal concentrations of spiked analyte." |
| Precision (Qualitative) | Acceptable within-run and total precision statistics, demonstrated by Coefficients of Variation (CV) for rates of controls and cutoff calibrator. | "Qualitative results, determined from rates for controls and cutoff calibrator, demonstrated within-run precision with coefficients of variation (CV) of 0.4% and total precision with CV ranging from 0.7 - 0.8%." |
| Precision (Semiquantitative) | Acceptable within-run and total precision statistics, demonstrated by Coefficients of Variation (CV) for concentrations of controls and cutoff calibrator. | "Semiquantitative results, determined from concentrations for controls and cutoff calibrator, demonstrated within-run precision with CV ranging from 1.6 - 2.2% and total precision with CV ranging from 3.0 - 3.8%." |
| Sensitivity | The lowest concentration of propoxyphene that can be distinguished from 0 ng/mL with a 95% confidence level should be below a certain threshold. | "The sensitivity level of the Emit® II Plus Propoxyphene Assay is less than 60 ng/mL. This level represents the lowest concentration of propoxyphene that can be distinguished from 0 ng/mL with a confidence level of 95%." |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample sizes for the test sets used in each performance study (comparative analysis, spiked sample recovery, precision, sensitivity). It describes the methodology (e.g., "known levels of propoxyphene, spiked at levels," "Negative human urine specimens were spiked").
The data provenance is not explicitly stated regarding country of origin. The studies appear to be retrospective in nature, as they involve testing urine samples (both clinical and spiked) in a laboratory setting to evaluate the assay's performance. There is no indication of a prospective study where the assay is used on real-time patient samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts or their qualifications for establishing ground truth within the studies described. For an in vitro diagnostic (IVD) device like this, ground truth is typically established by:
- Predicate device results: For the comparative analysis, the predicate device itself serves as a "ground truth" reference.
- Known spike concentrations: For spiked sample recovery, the known concentrations of propoxyphene added to the samples serve as the ground truth.
- Analytical methods: For sensitivity and precision, the ground truth is derived from the inherent analytical properties of the assay and statistical calculations.
4. Adjudication Method for the Test Set
No adjudication method (e.g., 2+1, 3+1, none) is mentioned. This is typical for IVD device performance studies where ground truth is established analytically (known concentrations, predicate device results) rather than by human interpretation requiring consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an imaging device or a system requiring human interpretation comparison, so MRMC studies are not applicable in this context.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are standalone performance studies of the assay itself. The results reported are direct measurements of the assay's ability to detect and quantify propoxyphene in urine, without human intervention in the analytical process or interpretation of raw signals for diagnosis. The assay yields a result (qualitative positive/negative, or a semiquantitative concentration), which then might be reviewed by a human, but the performance metrics here are about the assay's analytical capabilities.
7. The Type of Ground Truth Used
The types of ground truth used are:
- Predicate device results: For the comparative analysis.
- Known concentrations (spiking): For spiked sample recovery studies.
- Analytical definitions: For precision and sensitivity, the ground truth is based on the inherent analytical properties of the assay and statistical calculations to determine limits and variations.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of an algorithm or machine learning model. This is an immunoassay, not an AI/ML-based device. Therefore, the concept of a training set as a distinct dataset used to train an algorithm is not applicable here. The development and optimization of the assay would involve various experimental stages, but these are not referred to as "training sets."
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the AI/ML sense, this question is not applicable. The assay's parameters would have been optimized during its development through a series of experiments and iterations, likely involving known concentrations of propoxyphene and comparisons to reference methods, but this is part of the assay development process, not the training of a discrete algorithm.
§ 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).