(28 days)
Xenta Drug Screen Cup and Xenta Drug Screen Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drugs and drug metabolites in human urine at the following cut-off concentrations:
Test Barbiturates (BAR) Benzodiazepines (BZO) Amphetamine (AMP) Methadone (MTD) Oxycodone (OXY) Phencyclidine (PCP)
- Calibrator Secobarbital Oxazepam D-Amphetamine Methadone Oxycodone Phencyclidine
Cut-off level 300 ng/mL 300 ng/mL 1000 ng/mL 300 ng/mL 100 ng/mL 25 ng/mL
The tests contain two formats: 1) Test Cup and 2) Test Dipcard. The tests may be configured as single drug tests or multiple drug tests in any combination of the drug analytes listed in the table above. These tests are intended for in vitro diagnostics use. They are intended for prescription use.
The assays provide only a preliminary analytical test 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 indicated.
Xenta Drug Screen Cup and Xenta Drug Screen Dipcard are competitive binding, lateral flow immunochromatographic assays for the qualitative detection of Barbiturate, Benzodiazepine, Amphetamine, Methadone, Oxycodone, Phencyclidine at or above the cut-off levels as indicated. The tests are performed without the use of an instrument.
The test cup and test dipcard formats use identical test strips made with the same chemical formulation and manufacturing procedures.
The provided document describes the performance of the Xenta Drug Screen Cup and Xenta Drug Screen Dipcard for detecting various drugs in human urine. The study evaluates cross-reactivity, interference, effect of pH and specific gravity, precision, and accuracy.
Here's an breakdown of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria (Implicit) and Reported Device Performance
The document does not explicitly state "acceptance criteria" but rather presents a rigorous set of performance data that would generally be used to support claims of substantial equivalence. For immunoassays of this type, key performance indicators are typically precision (agreement at different concentrations, especially near the cutoff) and accuracy (agreement with a gold-standard confirmatory method like GC/MS).
Implicit Acceptance Criteria (based on common standards for such devices):
- Precision: High percentage of agreement (positive/negative results) for samples spiked at various concentrations, especially those near the cutoff (e.g., -25% and +25% of cutoff). For negative and very high positive concentrations, 100% agreement would generally be expected.
- Accuracy: High concordance with a confirmatory method (GC/MS) for clinical samples, particularly for drug-free, high positive, and discordant samples.
- Specificity (Cross-reactivity): Low or no cross-reactivity with structurally similar compounds and other common substances, or clearly defined cross-reactivity profiles.
- Robustness (Interference, pH, Specific Gravity): The device's performance should not be significantly affected by common interfering substances, varying urine pH, or specific gravity within physiological and expected ranges.
Reported Device Performance:
The document provides extensive data demonstrating the device's performance across these parameters. For brevity, here's a summary derived from the tables provided in section 8:
| Performance Parameter | Reported Performance (Summary from tables) |
|---|---|
| Precision (Agreement at cutoff) | Amphetamine (AMP) at 1000 ng/mL cutoff: Single Test Cup/Dipcard: 32-38 positive out of 60 (53-63%). Multi Test Cup/Dipcard: 32-38 positive out of 60 (53-63%). |
| Barbiturates (BAR) at 300 ng/mL cutoff: Single Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). Multi Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). | |
| Benzodiazepines (BZO) at 300 ng/mL cutoff: Single Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). Multi Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). | |
| Methadone (MTD) at 300 ng/mL cutoff: Single Test Cup/Dipcard: 32-38 positive out of 60 (53-63%). Multi Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). | |
| Oxycodone (OXY) at 100 ng/mL cutoff: Single Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). Multi Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). | |
| Phencyclidine (PCP) at 25 ng/mL cutoff: Single Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). Multi Test Cup/Dipcard: 34-38 positive out of 60 (57-63%). |
Note: Agreement is nearly 100% for samples significantly below (-75%, -50% cutoff) and significantly above (+50%, +75%, +100% cutoff) the cutoff. |
| Accuracy (Concordance with GC/MS) | For all drugs (AMP, BAR, BZO, MTD, OXY, PCP) and both device formats (Single/Multi Drug Test Cup and Dipcard), the device consistently showed:
- 0 false positives in drug-free samples.
- 0 false positives in samples less than half the cutoff.
- Very few false positives (0-1) and some false negatives (4-8) in the "Near Cutoff Negative" (between 50% below cutoff and cutoff concentration) category.
- Very few false positives (0) and some false negatives/positives (range varies, but generally consistent with expected +/- 25% cutoff performance) in the "Near Cutoff Positive" (between cutoff and 50% above cutoff concentration) category.
- 0 false negatives in "High Positive" samples (greater than 50% above the cutoff).
Specific discordant results are minimal and generally at concentrations very close to the cutoff.
In total, for each drug, 80 clinical samples were tested, with very high overall agreement for clearly negative or clearly positive samples. |
| Cross-reactivity | Detailed tables show the lowest concentration of various related compounds that produced a positive result. Percent cross-reactivity is calculated. E.g., L-Amphetamine: 2%, MDA: 50%, Hydrocodone: 3.3%. This is a comprehensive evaluation common for immunoassays. |
| Interference | "None of the compounds listed below were shown to interfere." (List includes numerous common medications and physiological substances at 100 µg/mL). |
| Effect of pH | "The results demonstrate that varying ranges of pH do not interfere with the performance of the test." (Tested pH range 3-9). |
| Effect of Specific Gravity | "The results demonstrate that varying ranges of urinary specific gravity do not affect the test result." (Tested SG 1.002 to 1.040). |
| Stability of Test Line | "The results show that the color T line... are stable from 3 to 50 minutes." (Suggested read time: 5 to 30 minutes). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set Sample Size:
- For each drug, for both single and multi-drug formats, and for both Test Cup and Test Dipcard:
- 9 concentrations (0, -75%, -50%, -25%, Cutoff, +25%, +50%, +75%, +100% of cutoff).
- 60 determinations per lot for each concentration (this is derived from 3 aliquots x 3 runs/day x 10 days x 2 operators/device type at each of the 3 sites, meaning 60 samples per lot, per concentration for each device type).
- Tested with 3 lots.
- Total precision observations for one drug and one device format (e.g., AMP on Single Test Cup) = 9 concentrations x 60 determinations/lot x 3 lots = 1620 observations.
- Total observations for all 6 drugs and 2 device types (Single Test Cup, Multi Test Cup, Single Test Dipcard, Multi Test Dipcard) multiplied by 1620 observations per format.
- For each drug, for both single and multi-drug formats, and for both Test Cup and Test Dipcard:
- Accuracy Test Set Sample Size:
- 80 clinical urine samples per drug (AMP, BAR, BZO, MTD, OXY, PCP) for each of the four device variants (Single Drug Test Cup, Multi Drug Test Cup, Single Drug Test Dipcard, Multi Drug Test Dipcard).
- Total accuracy samples = 80 samples/drug x 6 drugs = 480 clinical samples (with GC/MS confirmation). These 480 samples are then tested across the 4 device variants.
- Data Provenance:
- Clinical Urine Samples: "80 clinical urine samples collected all from sample place several hospitals and drug relief reformatory."
- Retrospective/Prospective: The description does not explicitly state retrospective or prospective collection for the clinical samples. However, given they were "collected all from sample place," it implies they were likely existing samples (retrospective) or collected for the specific purpose of the study (prospective), but the exact method isn't specified. The emphasis on blind labeling and randomization for testing suggests a controlled prospective-like application in the study even if samples were retrospectively sourced.
- Country of Origin: Not explicitly stated for specific samples, but the submitting company is "Xenta Biomedical Science Co., Ltd." located in Guangzhou, China.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- The ground truth for the clinical accuracy test set was established by Gas Chromatography/Mass spectrometry (GC/MS). GC/MS is considered the "preferred confirmatory method" and the gold standard for drug detection in urine.
- No human "experts" (e.g., radiologists) were used to establish the ground truth in this context; instead, a highly accurate analytical laboratory method (GC/MS) served as the gold standard. Therefore, the concept of "qualifications of those experts" does not directly apply in the way it would for image-based diagnostic devices. The expertise lies in the laboratory personnel performing and interpreting the GC/MS analysis.
4. Adjudication Method for the Test Set
- GC/MS was used as the confirmatory method to adjudicate the results of the rapid tests.
- For the precision study, samples were "blindly labeled by a nonparticipant" and "randomized prior to testing," indicating a blind comparison against the known spiked concentrations.
- For the accuracy study, clinical samples were also "blindly labeled by a nonparticipant" and "randomized prior to testing" against the GC/MS confirmed results.
- There's no mention of a traditional group adjudication method (e.g., 2+1, 3+1) involving multiple human readers of the rapid test, as the rapid test is interpreted visually by a single operator. Discordant results were analyzed by comparing the device result directly against the GC/MS result and the drug concentration.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of human readers improve with AI vs without AI assistance
- No, an MRMC comparative effectiveness study was not performed, nor would it be applicable for this type of device.
- This device is a qualitative lateral flow immunoassay for drug detection in urine, designed for visual interpretation. It is not an AI-assisted diagnostic imaging device for human interpretation like those typically evaluated in MRMC studies. Therefore, there's no AI component or human reader improvement analysis.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, in essence. The device itself is a "standalone" test in the sense that its performance (how accurately it detects drugs based on chemical reactions) is tested directly against gold standard methods (GC/MS) or known spiked concentrations.
- The interpretation step is visual, performed by a human operator, but the core performance data (cross-reactivity, precision, accuracy) reflect the inherent capability of the immunoassay itself to produce a detectable signal at certain concentrations. The studies described are primarily focused on this standalone performance of the test strip.
7. The Type of Ground Truth Used
- Laboratory Confirmatory Method (GC/MS): This was the primary gold standard ground truth for the clinical accuracy studies.
- Known Spiked Concentrations: For the precision studies, the ground truth was established by spiking drug-free urine with precisely measured concentrations of analytes, confirmed by GC/MS. This allows for a very controlled evaluation of the device's consistency and ability to detect at specific thresholds.
8. The Sample Size for the Training Set
- The document describes performance studies for the device, implying a final validation of a developed product. It does not mention a "training set" in the context of an algorithm or machine learning model.
- For a traditional immunoassay, there isn't a "training set" in the computational sense. The "training" for such a device involves the biochemical development and optimization of the reagents and test strip design. The provided data are for verification and validation of the final product.
9. How the Ground Truth for the Training Set Was Established
- As there is no "training set" in the context of an AI/machine learning algorithm, this question is not applicable. The development of an immunoassay involves optimizing antibody-antigen reactions and signal generation, which is a biochemical engineering process, not a data-driven model training process.
§ 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).