(78 days)
The AMPH Flex® reagent cartridge used on the Dimension clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.
The AMPH method provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order 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 Dade Behring Dimension® AMPH method is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge (Flex®) for use on the Dade Behring Dimension® clinical chemistry system.
The provided document does not explicitly state acceptance criteria in a quantitative format as commonly seen for medical device performance. Instead, it presents performance data by comparing the Dimension® Urine Amphetamines/Methamphetamine Screen Flex® (AMPH Flex®) reagent cartridge against a predicate device (Syva® Emit® II Plus Amphetamine Assay) and a reference method (GC/MS) at three different cutoffs (300, 500, and 1000 ng/mL). The "acceptance criteria" are implied by the agreement rates shown in the comparison tables.
Here's an analysis of the study based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
As explicit acceptance criteria (e.g., "must achieve >95% agreement") are not stated, the table below reflects the observed performance against the reference method (GC/MS). The implied acceptance is that the device demonstrates comparable or acceptable agreement with the gold standard (GC/MS).
Implied Acceptance Criteria and Reported Device Performance for AMPH Flex® Reagent Cartridge vs. GC/MS
| Cutoff (ng/mL) | Performance Metric (Agreement with GC/MS) | Reported AMPH Flex® Performance | Interpretation of Acceptance |
|---|---|---|---|
| 300 | Positive Agreement (Sensitivity) | 72/80 = 90% | Implied acceptance if sensitivity is deemed adequate for screening. |
| Negative Agreement (Specificity) | 49/49 = 100% | Implied acceptance if specificity is deemed adequate for screening. | |
| Discrepancy Analysis in ng/mL (Total cases: 129) | 8 False Negatives (GC/MS Positive, AMPH Flex® Negative) at this cutoff. | Further analysis of false negatives would inform acceptance. | |
| 500 | Positive Agreement (Sensitivity) | Data for "+" in AMPH Flex® vs. GC/MS is partially missing. The table for GC/MS comparison for cutoff 500 ng/mL does not explicitly show the total positives and negatives from GC/MS. The first row in the table is corrupted but seems to be a header. Manual counting of discrepant values suggests more data points are needed to complete this table. | Cannot calculate without complete table data. |
| Negative Agreement (Specificity) | Data for "-" in AMPH Flex® vs. GC/MS is partially missing. | Cannot calculate without complete table data. | |
| Discrepancy Analysis in ng/mL (Total cases: 129) | 14 False Negatives explicitly listed in the discrepant table. | Further analysis of false negatives would inform acceptance. | |
| 1000 | Positive Agreement (Sensitivity) | Data for "+" in AMPH Flex® vs. GC/MS is partially missing. The table is corrupted. | Cannot calculate without complete table data. |
| Negative Agreement (Specificity) | Data for "-" in AMPH Flex® vs. GC/MS is partially missing. | Cannot calculate without complete table data. | |
| Discrepancy Analysis in ng/mL (Total cases: 169) | 14 False Negatives explicitly listed in the discrepant table. | Further analysis of false negatives would inform acceptance. |
Note on missing data: The tables for cutoffs 500 ng/mL and 1000 ng/mL comparing AMPH Flex® to GC/MS are significantly corrupted in the provided text, making it impossible to fully populate the performance metrics. For example, for the 500 ng/mL cutoff against GC/MS there's a row 0 | | | | | Amer | A ARA (C (C) (C) (C) AN ANNUAL (C) 21 | and the same and the state of the states | | - | ---------------------------------------------------------------------------- 8 ! . instead of proper counts. The 1000 ng/mL cutoff against GC/MS similarly has corrupted table data.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- For 300 ng/mL cutoff: 129 native urine specimens
- For 500 ng/mL cutoff: 129 native urine specimens
- For 1000 ng/mL cutoff: 169 native urine specimens (with 129 having separate amphetamine and methamphetamine values suitable for SAMHSA confirmation guidelines)
- Data Provenance: The data consists of "native urine specimens." No country of origin is specified. The study is retrospective, as it analyzes existing urine specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- The document does not explicitly state the number of experts or their qualifications for establishing the ground truth.
- The ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS). While GC/MS is a laboratory method, expert interpretation of GC/MS results (e.g., "Positives by GC/MS were determined by using the criteria...") is implied. However, the document does not detail the personnel or their qualifications involved in this interpretation.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method involving human reviewers for discrepancies between the AMPH Flex® result and the GC/MS result. Discrepant values are simply listed with their GC/MS and AMPH Flex® (and sometimes predicate device) readings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size of Human Improvement with AI vs. without AI Assistance
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic test, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
- Yes, the performance study effectively represents a standalone performance. The AMPH Flex® reagent cartridge on the Dimension® clinical chemistry system is an automated in-vitro diagnostic device. Its performance is evaluated directly against the reference method (GC/MS) without human interpretation affecting the device's analytical result. The results ("Positives" or "Negatives" by AMPH Flex®) are direct outputs of the automated system.
7. The Type of Ground Truth Used
- The ground truth used is Gas Chromatography/Mass Spectrometry (GC/MS), which is considered the preferred confirmatory method for amphetamines in urine. The criteria for defining a positive by GC/MS are explicitly stated for each cutoff level (e.g., "amphetamine plus methamphetamine > 300 ng/mL" for the 300 ng/mL cutoff). This can be classified as a definitive laboratory method (gold standard).
8. The Sample Size for the Training Set
- The document does not provide any information regarding a training set or its sample size. This type of regulatory submission (510(k)) for a laboratory diagnostic test typically focuses on validation data to demonstrate substantial equivalence, rather than detailing the internal development and training of a machine learning algorithm.
9. How the Ground Truth for the Training Set Was Established
- As no information about a training set is provided, the method for establishing its ground truth is also not described.
§ 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).