(122 days)
The Methadone Metabolite Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of Methadone Metabolite in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Methadone Metabolite Enzyme Immunoassay 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. Clinical consideration and professional judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
LZI's Methadone Metabolite Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibody that can detect Methadone Metabolite (EDDP) in human urine with minimal cross-reactivity to various, common prescription drugs and abused drugs.
The assay is based on competition between Methadone Metabolite labeled with glucose-6phosphate dehydrogenase (G6PDH) enzyme and free drug from the urine sample for a fixed amount of specific antibody. In the absence of free drug from the urine sample the specific antibody binds to the drug labeled with G6PDH enzyme causing a decrease in enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.
Here's an analysis of the acceptance criteria and study detailed in the provided document for the Lin-Zhi International, Inc.'s Methadone Metabolite Enzyme Immunoassay ({0}-{6}):
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal acceptance criteria with numerical targets. Instead, it demonstrates substantial equivalence by comparing the performance characteristics of the LZI device to its predicate device (DRI/Microgenics Corp.'s Methadone Metabolite Enzyme Immunoassay) and showing "acceptable results." The criteria are implied by the performance metrics measured.
| Performance Characteristic | Implicit Acceptance Criterion | LZI's Methadone Metabolite EIA Reported Performance |
|---|---|---|
| Precision (Within Run) | Low %CV (indicating consistency) | Qualitative: |
| Negative: %CV = 0.73 | ||
| 225 ng/mL: %CV = 0.69 | ||
| 300 ng/mL: %CV = 0.72 | ||
| 375 ng/mL: %CV = 0.78 | ||
| 1000 ng/mL: %CV = 0.75 | ||
| Semi-quantitative: | ||
| Quantitates accurately | 225 ng/mL: %CV = 3.88 | |
| 300 ng/mL: %CV = 4.50 | ||
| 375 ng/mL: %CV = 3.40 | ||
| Precision (Run-To-Run) | Low %CV (indicating consistency) | Qualitative: |
| Negative: %CV = 0.74 | ||
| 225 ng/mL: %CV = 0.81 | ||
| 300 ng/mL: %CV = 0.47 | ||
| 375 ng/mL: %CV = 0.63 | ||
| 1000 ng/mL: %CV = 0.93 | ||
| Semi-quantitative: | ||
| Quantitates accurately | 225 ng/mL: %CV = 3.59 | |
| 300 ng/mL: %CV = 3.62 | ||
| 375 ng/mL: %CV = 3.19 | ||
| Sensitivity | Low detection limit | 15 ng/mL |
| Accuracy (Qualitative) | High agreement with a reference method | Vs. GC/MS (n=139): |
| Positive: 100 % agreement | ||
| Negative: 100 % agreement | ||
| Analytical Recovery (Qualitative) | 100% accuracy on positive vs. negative tests | 100% accuracy |
| Analytical Recovery (Semi-quantitative) | Quantitation within a specified percentage of nominal concentration | Quantitates within ±15% of nominal concentration between 30 ng/mL and 900 ng/mL. Average 95.0 % recovery at 225 ng/mL, Average 105.4 % recovery at 375 ng/mL. |
| Specificity | Comparable to predicate device | Comparable to the predicate device. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Accuracy Study: The accuracy study against GC/MS involved n=139 samples.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is implied to be laboratory-based validation data.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
- The ground truth for the test set (specifically for the accuracy study) was established by Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is an analytical chemical method, not an expert human interpretation. Therefore, the concept of "number of experts" and their "qualifications" is not applicable in this context.
4. Adjudication Method for the Test Set
- Since the ground truth was established by an objective analytical method (GC/MS), there was no human adjudication reported or necessary for the test set.
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
- No MRMC study was performed. This device is an in-vitro diagnostic (immunoassay) for methadone metabolites, not an AI-based imaging or interpretive device that would typically involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
- This device is a standalone algorithm/kit. The performance data presented (precision, sensitivity, accuracy, recovery, specificity) represents the performance of the immunoassay system itself, without direct human interpretive "in-the-loop" performance affecting the result generation, although human operators perform the test and interpret the final qualitative/semi-quantitative output.
7. The Type of Ground Truth Used
- The primary ground truth used for accuracy comparison was Gas Chromatography/Mass Spectrometry (GC/MS). This is an objective, gold-standard analytical method for confirming drug presence and concentration.
8. The Sample Size for the Training Set
- The document does not mention a training set in the context of machine learning or AI. This is a conventional immunoassay where the reagents are formulated and optimized, but not "trained" on data in the same way an AI algorithm is. The development and optimization of the assay likely involved numerous samples during its formulation, but this is distinct from "training data" for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as there is no "training set" in the context of an AI/ML algorithm mentioned for this immunoassay device.
§ 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).