(223 days)
The DRI Amphetamines Assay is intended for the qualitative or semi-quantitative determination of amphetamine and methamphetamine in human urine. The assay has cutoff levels of 500 and 1000 ng/mL. The assay provides a simple and rapid analytical screening procedure for detecting amphetamine and methamphetamine in urine on automated clinical analyzers. The assay is calibrated with methamphetamine.
This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used 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 positive results are used.
The DRI Amphetamines Assay is a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies, which can detect amphetamine and/or methamphetamine in urine with minimal cross-reactivity to various over-the-counter structurally unrelated compounds. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the 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. In the presence of free drug, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting 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.
Here's a breakdown of the acceptance criteria and the study details for the Thermo Scientific DRI® Amphetamines Assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Design Input Specifications) | Reported Device Performance (Achieved) |
|---|---|---|
| Precision (Qualitative) | All negative samples recover as negative, all positive samples recover as positive. | All negative samples recovered as negative and all positive samples recovered as positive. |
| Precision (Semi-Quantitative) | Within-run %CV and total-run %CV meet design specifications. | Within run %CV for was less than or equal to 6.2% and the total run %CV was less than or equal to 6.9%. (The specific numerical design specifications for %CV are not explicitly stated, but the submission claims they were met.) |
| Accuracy / Method Comparison | Greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays. | Greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays. (Note: Discordant results were observed for individual analyte detection due to the assay's 100% cross-reactivity to both amphetamine and methamphetamine, but this was explained and seemingly accepted within the context of the overall agreement and intended use of a screening assay.) |
| Dilution Recovery (Linearity) | Recovery less than ±4% error of the expected value for levels tested throughout the assay range (0 to 2000 ng/ml). | Recovery was less than ±4% error of the expected value for levels tested from 0 to 2000 ng/ml. The assay dilutes in a linear fashion. |
| On-Board Open Vial Reagent Stability | Reagents stored on the analyzer are stable for a minimum of 60 days. | Reagents stored on the analyzer are stable for a minimum of 60 days. |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: The document does not provide specific numerical sample sizes for the precision, accuracy/method comparison, dilution recovery, or stability studies. It broadly states "Samples spiked with d-amphetamine and d-methamphetamine were tested" for precision, and "Samples were tested by DRI qualitative and semi-quantitative assay and compared to GC/MS" for method comparison.
- Data Provenance: Not explicitly stated. Given it's a 510(k) submission for a diagnostic kit, the samples would likely be human urine samples, potentially spiked or clinical samples. It's common for such studies to be conducted internally or at contract research organizations in the country where the manufacturer is located (USA, in this case, Microgenics Corporation is in Fremont, CA). The study type appears to be prospective as it involves controlled testing to demonstrate performance.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications:
- Number of Experts: Not applicable in the context of this device.
- Qualifications of Experts: Not applicable. For drug screening assays, the "ground truth" is typically established by a highly specific and sensitive reference method.
4. Adjudication Method for the Test Set:
- Adjudication Method: Not applicable. The ground truth is established by a reference analytical method (GC/MS) rather than human adjudication of interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- MRMC Study: No, this type of study was not performed. MRMC studies are typically for image-based diagnostic devices where multiple human readers interpret cases. This device is an in-vitro diagnostic assay.
- Effect Size of Human Readers with/without AI Assistance: Not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study was done:
- Standalone Study: Yes, the performance studies described (Precision, Accuracy/Method Comparison, Dilution Recovery, Stability) represent the standalone performance of the device/assay without human interpretation beyond standard laboratory procedures (e.g., loading samples, reading results from an automated analyzer). The assay itself is an "algorithm" in the chemical sense, providing a result.
7. The Type of Ground Truth Used:
- Type of Ground Truth: The primary ground truth used for method comparison (accuracy) was Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is widely considered the gold standard for confirming the presence and concentration of drugs in urine samples due to its high specificity and sensitivity. For precision, the "ground truth" was derived from the known concentrations of spiked samples.
8. The Sample Size for the Training Set:
- Sample Size for Training Set: The document does not specify a separate "training set" or its size. For an in-vitro diagnostic assay like the DRI Amphetamines Assay, the development process might involve numerous experiments and optimization steps that could be considered analogous to "training." However, the 510(k) summary focuses on the final validation/test set. The assay itself is based on a chemical reaction and antibody-antigen binding kinetics, not a machine learning algorithm that requires a distinct training dataset in the same way.
9. How the Ground Truth for the Training Set Was Established:
- Ground Truth for Training Set: Not explicitly stated as a distinct "training set" in the context of machine learning. The "ground truth" during the development and optimization of such an assay would involve known concentrations of amphetamines and methamphetamines in urine, validated through highly accurate analytical methods, to ensure the assay's reagents, reaction conditions, and calibration curve are optimized to accurately detect and quantify the target analytes. This iterative process is part of the assay's design and engineering.
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).