(62 days)
Healgen Oxazepam Test is an immunochromatographic assay for the qualitative determination of Oxazepam (a drug in the benzodiazepine class) in human urine at a Cut-Off concentration of 300 ng/m L. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
Healgen Morphine Test is an immunochromatographic assay for the qualitative determination of morphine (a drug in the opiate class) in human urine at a Cut-Off concentration of 2000 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the presult is positive. For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
Healgen Oxazepam Test and Healgen Morphine Test are immunochromatographic assays for Oxazepam and Morphine. Each assay test is a lateral flow system for the qualitative detection of Oxazepam and Morphine (target analyte) in human urine. The products are in vitro diagnostic devices, which come in the form of: Strips, Cassettes, DipCards, or Cups. Each product contains a Test Device (in one of the four formats), and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.
This document describes the performance characteristics and acceptance criteria for the "Healgen Oxazepam Test" and "Healgen Morphine Test," which are immunochromatographic assays for the qualitative determination of Oxazepam and Morphine in human urine.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria & Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as pass/fail thresholds in a dedicated table format. Instead, it presents performance data that implicitly serves as the proof of meeting intended performance. The key performance metrics evaluated are precision and method comparison (clinical sample testing) near the cut-off concentrations, and lay-user study accuracy.
I've extracted the relevant performance values. For "acceptance criteria," I'll interpret this as the implied high accuracy expected from such diagnostic tests.
| Performance Metric | Specific Test and Concentration | Implied Acceptance Criteria (e.g., high agreement with GC/MS, low false rates) | Reported Device Performance (Oxazepam) | Reported Device Performance (Morphine) |
|---|---|---|---|---|
| Precision | Samples at -100% to -25% of cut-off | 100% agreement with expected negative result | 50-/0+ (50 negative, 0 positive) across all concentrations (-100%, -75%, -50%, -25%) and all formats (Strip, Cassette, Dip Card, CUP) for all 3 lots tested. | 50-/0+ across all concentrations (-100%, -75%, -50%, -25%) and all formats (Strip, Cassette, Dip Card, CUP) for all 3 lots tested. |
| Precision | Samples at +25% to +100% of cut-off | 100% agreement with expected positive result | 50+/0- (50 positive, 0 negative) across all concentrations (+25%, +50%, +75%, +100%) and all formats (Strip, Cassette, Dip Card, CUP) for all 3 lots tested. | 50+/0- across all concentrations (+25%, +50%, +75%, +100%) and all formats (Strip, Cassette, Dip Card, CUP) for all 3 lots tested. |
| Precision | Samples at Cut-off concentration | High percentage of correct classifications (mix of positive/negative expected) | Oxazepam Strip: 22-/28+ (22 negative, 28 positive); Cassette: 24-/26+; Dip Card: 18-/32+; CUP: 20-/30+ (across 3 lots each). This indicates expected variability near the cutoff. | Morphine Strip: 18-/32+; Cassette: 22-/28+; Dip Card: 22-/28+; CUP: 20-/30+ (across 3 lots each). This indicates expected variability near the cutoff. |
| Method Comparison (Clinical Samples) | Agreement with GC/MS for negative samples (Negative, Low Negative, Near Cutoff Negative) | Very high agreement with GC/MS | Oxazepam (all formats, all 3 viewers): All samples in these categories (10 + 15 + 15 = 40 samples per viewer) were correctly identified as negative (e.g., "10", "15", "15" in negative rows). | Morphine (all formats, all 3 viewers): All samples in these categories (10 + 16 + 14 = 40 samples per viewer) were correctly identified as negative (e.g., "10", "16", "14" in negative rows). |
| Method Comparison (Clinical Samples) | Agreement with GC/MS for positive samples (Near Cutoff Positive, High Positive) | Very high agreement with GC/MS | Oxazepam (all formats, all 3 viewers): Generally high agreement, with some discordant results near cutoff. For example, Strip format: 14/16 positive in "Near Cutoff Positive", 24/24 positive in "High Positive." See detailed discordant rows for exceptions. | Morphine (all formats, all 3 viewers): Generally high agreement, with some discordant results near cutoff. For example, Strip format: 13/17 positive in "Near Cutoff Positive", 23/23 positive in "High Positive." See detailed discordant rows for exceptions. |
| Lay-user Study (Accuracy) | Overall correct results for each concentration level tested (-100% Cutoff to +75% Cutoff) | ≥ 90% correct for all concentrations | Generally 90-100% correct results across all concentration levels and all formats. For example, -25% Cutoff: 90-95% correct; +25% Cutoff: 90-95% correct. Others 100%. | Generally 90-100% correct results across all concentration levels and all formats. For example, -25% Cutoff: 90% correct; +25% Cutoff: 90-95% correct. Others 100%. |
| Lay-user Study (Instructions) | Ease of understanding instructions | Easily understood by lay users | All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid Grade Level: 7. | All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid Grade Level: 7. |
2. Sample sizes used for the test set and the data provenance:
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Precision Studies (Analytical Performance):
- Test Set Size: For each drug (Oxazepam and Morphine), for each format (Strip, Cassette, Dip Card, CUP), and for each of the 3 lots, 50 samples were tested at each of 9 concentrations (-100%, -75%, -50%, -25%, Cut-off, +25%, +50%, +75%, +100% of cut-off).
- Total precision samples per drug: (9 concentrations * 50 samples/conc * 4 formats * 3 lots) = 5400 samples
- Total precision samples (Oxazepam + Morphine): 10,800 samples.
- Data Provenance: The document states "samples were prepared by spiking drug in negative samples." "These samples were tested using three batches of each device." The provenance (country of origin), whether retrospective or prospective, is not explicitly stated for these analytical samples, but they appear to be experimentally prepared rather than naturally occurring clinical samples.
- Test Set Size: For each drug (Oxazepam and Morphine), for each format (Strip, Cassette, Dip Card, CUP), and for each of the 3 lots, 50 samples were tested at each of 9 concentrations (-100%, -75%, -50%, -25%, Cut-off, +25%, +50%, +75%, +100% of cut-off).
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Method Comparison Studies (Clinical Samples):
- Test Set Size: For each drug (Oxazepam and Morphine), and for each format (Strip, Cassette, Dip Card, CUP), 80 "unaltered clinical samples" (40 negative and 40 positive) were tested.
- Total method comparison samples per drug: (80 samples * 4 formats) = 320 samples.
- Total method comparison samples (Oxazepam + Morphine): 640 samples.
- Data Provenance: "unaltered clinical samples." The geographic origin of these clinical samples is not specified. They appear to be retrospective as they were collected and then blind labeled for testing.
- Test Set Size: For each drug (Oxazepam and Morphine), and for each format (Strip, Cassette, Dip Card, CUP), 80 "unaltered clinical samples" (40 negative and 40 positive) were tested.
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Lay-user Study:
- Test Set Size: 140 lay persons for Oxazepam devices, and 140 lay persons for Morphine devices. Each participant was given 1 blind-labeled sample.
- For Oxazepam and Morphine, each lay person tested one sample at one of 7 concentrations (-100%, -75%, -50%, -25%, +25%, +50%, +75%, of cut-off).
- For each concentration level, 20 samples were tested. So, 20 * 7 = 140 samples were tested per drug.
- Data Provenance: The study was "performed at three intended user sites." The geographic origin is not specified. The samples were "prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens." This indicates a prospective experimental design using prepared urine samples, not naturally occurring clinical samples.
- Test Set Size: 140 lay persons for Oxazepam devices, and 140 lay persons for Morphine devices. Each participant was given 1 blind-labeled sample.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
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For Precision Studies & Lay-user Studies: The document states that drug concentrations in the prepared samples were "confirmed by GC/MS." GC/MS (Gas Chromatography/Mass Spectrometry) is a highly reliable analytical chemistry method, and its results are considered the gold standard for confirming drug concentrations. The "experts" here are the calibrated GC/MS instrument and the analytical chemists operating and interpreting it. Specific expert qualifications are not detailed, but it's implied they adhere to standard laboratory practices for GC/MS.
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For Method Comparison Studies (Clinical Samples): The ground truth was established by "GC/MS results." Similar to above, GC/MS is the reference method, implying that the ground truth was derived from this analytical technique rather than human expert interpretation of the test device itself.
4. Adjudication method for the test set:
- Precision Studies & Lay-user Studies: No explicit adjudication method is mentioned. The ground truth (GC/MS confirmation) is considered definitive for these prepared samples.
- Method Comparison Studies: The comparison was directly against "GC/MS results," which serves as the independent truth. The results from each of the three "laboratory assistants" (viewers) were compared individually to the GC/MS result. There was no listed adjudication process among the viewers; their individual agreement/disagreement with GC/MS is reported.
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, an MRMC comparative effectiveness study was not done. This document describes a traditional in-vitro diagnostic device (lateral flow immunoassay for drugs of abuse) and its validation. It is not an AI-assisted diagnostic device, nor does it involve human readers interpreting images or data with and without AI assistance. The "viewers" in the method comparison study are "laboratory assistants" performing the test and visually reading the results, not interpreting complex medical images.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Not applicable in the context of AI/algorithms. This device is a rapid, visual immunochromatographic assay. Its "performance" is inherently linked to human observation of the test lines. There is no underlying algorithm separate from the chemical reaction displayed visually. The "standalone" performance is essentially the listed "Precision" and "Method Comparison" results, where the device itself (the chemical immunoassay) is assessed for its ability to correctly manifest positive/negative results under various conditions, which are then read by a human.
7. The type of ground truth used:
- GC/MS (Gas Chromatography/Mass Spectrometry) results were used as the gold standard ground truth for both the precision studies (prepared samples) and the method comparison studies (clinical samples). This is a highly accurate and quantitative analytical method for drug concentration determination.
8. The sample size for the training set:
- Not applicable. This document describes a traditional immunochromatographic assay, not a machine learning or artificial intelligence model. Therefore, there is no "training set" in the computational sense. The device's "training" is inherent in its chemical design and manufacturing process, optimized through R&D and quality control, not through data-driven learning.
9. How the ground truth for the training set was established:
- Not applicable. As established in point 8, there is no "training set" for an AI model. For the development and verification of such an immunoassay, the "ground truth" would be established through established chemical and biological assays, often using purified standards and reference methods like GC/MS (as seen in the performance validation), during the manufacturing and R&D phases to ensure the reagents and test strip components function as intended. However, this is part of the product development and quality control, not a "training set" for an algorithm.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).