(302 days)
The Methadone Metabolite Immunoassay is intended to be used for the qualitative and semi-quantitative determination of the presence of Methadone Metabolite (2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine or EDDP) in human urine at cutoffs of 300 and 1000 ng/mL. The semi-quantitative range of the assay is 31-2000 ng/mL. The assay provides a simple and rapid analytical screening procedure to detect methadone metabolite in human urine.
The subject device, the DR1 Methadone Metabolite Enzyme Assay, is a ready-to-use, liquid homogeneous enzyme immunoassay. The assay uses specific antibodies that detect EDDP in human urine without cross-reactivity to the parent drug, methadone. The assay is based on the competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH), and free drug from the urine sample for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the drug labeled with G6PDH and causes a decrease in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and the enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH. The subject DRI® Methadone Metabolite Enzyme Assay utilizes a new monoclonal antibody and enzyme-conjugate, with increased reagent stability and calibrator and control separations.
Here's a breakdown of the acceptance criteria and the study information based on the provided text:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Accuracy: Agreement with predicate device | 100% agreement (Predicate device: 57 true positives, 54 true negatives) |
| Accuracy: Agreement with GC/MS | 95% agreement (69 true positives, 73 true negatives) |
| Total Imprecision (Predicate Device) | ≤ 0.8% CV across 4 levels (0, 300, 1000, 2000 ng/mL) |
| Total Imprecision (Subject Device) | ≤ 0.9% CV across 6 levels (150, 300, 500, 750, 1000, 1250 ng/mL) |
| Total Imprecision (Subject Device, dose mode) | ≤ 5.7% CV |
| Assay Sensitivity | Approximately 31 ng/mL |
| Intra- and Inter-assay Reproducibility | ≤ 5.7% |
| Linearity | Up to 2000 ng/mL |
| Adequate separation for 300 ng/mL cutoff | Demonstrated for specimens between 150 and 500 ng/mL |
| Adequate separation for 1000 ng/mL cutoff | Demonstrated for specimens between 750 and 1250 ng/mL |
| Cross-reactivity: Methadone | Does not cross-react |
| Interference: Common endogenous substances, urinary pH, unrelated compounds | No deleterious effect |
| Interference: Potentially cross-reacting compounds | No deleterious effect |
Study Details
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Sample size used for the test set and the data provenance:
- Accuracy (comparison to predicate device): 111 samples (57 true positives, 54 true negatives). Data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Accuracy (comparison to GC/MS): 142 samples (69 true positives, 73 true negatives). Data provenance is not specified.
- Imprecision studies: The number of unique samples is not explicitly stated. Instead, it refers to "4 levels of analyte concentration" for the predicate and "6 levels of analyte concentration" for the subject device, suggesting controlled spiked samples or pooled samples at specific concentrations rather than a large set of varied patient samples for this particular aspect.
- Sensitivity, reproducibility, linearity, clinical accuracy: Established through "a series of laboratory and clinical studies." The specific sample sizes for each of these broader categories are not detailed beyond the accuracy numbers mentioned above. The type of study (retrospective or prospective) is not explicitly stated, but "clinical studies" for accuracy suggest the use of patient samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable/Not mentioned. The ground truth for accuracy was established using a "commercial EIA Assay" (for the predicate comparison) and the "GC/MS reference method" (for the subject device comparison). These are analytical reference methods, not expert human readers.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. The ground truth was established by laboratory reference methods (commercial EIA and GC/MS), not through human adjudication.
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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:
- No. This device is an in vitro diagnostic (IVD) immunoassay, which is an automated or semi-automated laboratory test. It does not involve human readers interpreting images or data where AI assistance would be relevant for "improving" reader performance.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance data presented (accuracy, imprecision, sensitivity, reproducibility, linearity, specificity) represent the standalone performance of the DRI® Methadone Metabolite Enzyme Assay. As an IVD, it is designed to operate primarily as an algorithm/assay without human interpretive input for the final result (though human oversight, calibration, and QC are essential).
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Analytical Reference Methods:
- For the predicate device comparison: a "commercial EIA Assay."
- For the subject device comparison: "GC/MS reference method" (Gas Chromatography/Mass Spectrometry), which is considered the gold standard for confirmatory drug testing.
- Analytical Reference Methods:
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The sample size for the training set:
- Not explicitly stated. The document describes performance characteristics and studies (e.g., sensitivity, reproducibility, linearity, clinical accuracy), but it does not detail a separate "training set" as one would typically discuss for machine learning models. For an immunoassay, the "training" analogous process involves assay development, optimization, and validation using various samples to establish performance parameters, but not in the sense of a distinct, labeled training dataset for an AI algorithm.
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How the ground truth for the training set was established:
- Not applicable in the context of a "training set" for an AI algorithm. The development and optimization of the immunoassay likely involved using known spiked samples, clinical samples characterized by reference methods (like GC/MS), and internal controls to optimize reagent concentrations, antibody specificity, and overall assay performance.
§ 862.3620 Methadone test system.
(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).