(14 days)
The Pan Probe Biotech LiveSure™ Methamphetamine Screen Test Card and Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow immuno-chromatographic competitive urinary assays for the detection of Methamphetamine (MET) and its analogs or metabolites in human urine at the NIDA (National Institute on Drug Abuse) and SAMHSA (Substance Abuse and Mental Health Services Administration) cut-off level of 1,000 ng MET/ml. These tests are intended for visual, qualitative IVD screening, for professional use only, and are not intended for quantitative results, nor for over the counter sales. These screen tests for Methamphetamine, provide only preliminary qualitative analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. NIDA and SAMHSA have established gas chromatographic/mass spectrometry (GC/MS) as the preferred confirmatory method. Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.
The Pan Probe Biotech LiveSure™ Methamphetamine Screen Test and Test Strip (i.e., LiveSure™ Methamphetamine) are rapid qualitative competitive chromatographic immunoassays in which a chemically labeled drug conjugate competes with Methamphetamine drug, analogs or metabolites that may be present in test urinary samples for limited specific antibody binding sites. LiveSure™ Methamphetamine devices contain a unique membrane that has been pre-coated both with Methamphetamine drug conjugate at the test band, and have a builtin reference band with second antibody as a system control band. A pink colored anti-Methamphetamine monoclonal antibody-colloidal gold conjugate pad is placed on the right side of the test strip. In the absence of Methamphetamine drug, analogs or metabolites in the pink colored antibody-colloidal gold conjugate moves chromatographically along with the urinary sample on the capillary action. The antibodycolloidal gold conjugate binds to drug conjugate, forming an antibody-antigen complex binds to drug conjugate as a captured reagent at the test region and produces a visible pink colored band. When Methamphetamine is present in a test urine, that drug, analog or metabolite antigen competes with Methamphetamine conjugate at the test band region for the limited antibody sites on the antibody-colloidal gold conjugate. When a sufficient concentration of unnary Methamphetamine drug is present, it blocks limited antibody binding sites. This blockage-binding prevents attachment of pink colored antibody-colloidal gold conjugate to the Methamphetamine drug conjugate zone located at the LiveSure™ Methamphetamine test band region. To serve as a procedural control, a pink colored band in a control region will always appear regardless of presence of Methamphetamine in samples. Thus, negative unne samples produces two pink colored bands, while positive urine samples produce only one pink colored band.
The Pan Probe Biotech LiveSure™ Methamphetamine Screen Test Card and Test Strip are in vitro diagnostic devices intended for the qualitative detection of Methamphetamine, its analogs, or metabolites in urine samples.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in a quantitative form (e.g., "sensitivity must be >X%"), but rather implied through a comparison with a predicate device (EMIT® II Assay) and a gold standard (GC/MS). The performance is presented as a comparison to these methods.
| Metric | Acceptance Criteria (Implied) | LiveSure™ Methamphetamine Test Card Performance | LiveSure™ Methamphetamine Test Strip Performance | EMIT® II Assay Performance |
|---|---|---|---|---|
| Agreement with GC/MS (quantitative positive results) | 100% agreement with positive GC/MS results, and high agreement with negative GC/MS results, with overall accuracy comparable to or superior to predicate. | 100% | 100% | 100% |
| Agreement with GC/MS (negative results) | High agreement with negative GC/MS results. | 98.2% | 97.0% | 96.4% |
| Agreement with EMIT® II (positives) | High agreement with EMIT® II positives. | 97.8% | 99.3% | N/A |
| Specificity vs. EMIT® II (negatives) | High specificity compared to EMIT® II negatives. | 98.2% | 98.2% | N/A |
| False Positives/Negatives (within ±25% of 1000 ng/ml cut-off) | No false positives or false negatives. | 0 false positives, 0 false negatives | 0 false positives, 0 false negatives | 1 false positive (below 750 ng/ml), 3 false negatives (above 1001 ng/ml) |
| Overall Accuracy vs. GC/MS | Comparable or superior to predicate. | 99.0% (297/300) | 98.3% (295/300) | 97.0% (291/300) |
| Equivalence to EMIT® II Assay | Data essentially showing equivalency. | Considered equivalent or superior | Considered equivalent or superior | N/A |
2. Sample Size Used for the Test Set and the Data Provenance
- Sample Size for Test Set: 300 urine samples.
- Data Provenance: The data was obtained from "independent clinical testing" conducted at an "external reference laboratory." The country of origin is not explicitly stated, but given the submission is to the U.S. FDA, it is likely that the study was conducted within the United States or at a facility that complies with U.S. regulatory standards. The study appears to be retrospective, as a set of 300 urine samples were tested against the new devices, the predicate, and GC/MS.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS) analysis. GC/MS is a laboratory analytical method and does not involve human experts in the same way as an imaging study. Therefore, the concept of "number of experts" or their "qualifications" for establishing GC/MS ground truth is not applicable. The GC/MS results are considered the definitive, quantitative ground truth.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by GC/MS, which is an objective chemical analysis, not a subjective human interpretation requiring adjudication.
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
Not applicable. This is an in vitro diagnostic device for chemical analysis, not an imaging device or AI-assisted diagnostic tool that involves human readers interpreting results. The device itself provides a qualitative "positive" or "negative" indication.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study is inherently a standalone performance evaluation. The LiveSure™ Methamphetamine Screen Test Card and Test Strip are designed to provide a direct readout (bands appearing or not appearing), and their performance was assessed directly against reference methods (EMIT® II and GC/MS) without human interpretation affecting the device's output. While a human reads the results from the test strip, the "performance" here refers to the accuracy of the chemical reaction in producing the correct visual outcome.
7. The Type of Ground Truth Used
The primary and most robust ground truth used was Gas Chromatography/Mass Spectrometry (GC/MS) results, which provided quantitative confirmation of Methamphetamine presence and concentration.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. This is an immunoassay device, not a software algorithm that undergoes a training phase with a dataset. The development and optimization of the immunoassay reagents and design would have involved internal testing and validation, but this is not typically referred to as a "training set" in the way it is for AI/ML.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" with established ground truth is not directly applicable to this type of immunoassay device. The device's performance characteristics (e.g., antibody specificity, cut-off levels) would have been established through internal R&D using various methods and known concentrations of analytes and interferents, but not through a formal "training set" in the data science sense.
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).