(73 days)
Rapid Single/Multi-drug test Cup and Rapid Single/Multi-drug test Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drug metabolites in human urine at the following cut-off concentrations:
| Test | Calibrator | Cut-off level |
|---|---|---|
| Marijuana (THC) | Delta-9-THC-COOH | 50ng/mL |
| Cocaine (COC) | Benzolecgonine | 300ng/mL |
| Amphetamine (AMP) | D-Amphetamine | 1000ng/mL |
| Methamphetamine (MET) | D-Methamphetamine | 1000ng/mL |
| Morphine 2000 (MOP) | Morphine | 2000ng/mL |
| Barbiturates (BAR) | Secobarbital | 300ng/mL |
| Benzodiazepines (BZO) | Oxazepam | 300ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 3,4-Methylenedioxymethamphetamine | 500ng/mL |
| Methadone (MTD) | Methadone | 300ng/mL |
| Oxycodone (OXY) | Oxycodone | 100ng/mL |
| Phencyclidine (PCP) | Phencyclidine | 25ng/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 including point of care sites and over-the-counter use. The tests will yield preliminary positive results when prescription drugs Barbiturates, Benzodiazepine, and Methadone are ingested, even at or above therapeutic doses. There are no uniformly recognized drug levels for Barbiturates and Benzodiazepine in urine.
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.
Rapid Single/Multi-drug Test Cup and Rapid Single/Multi-drug Test Dipcard are competitive binding, lateral flow immunochromatographic assays for the qualitative detection of Amphetamine, Cocaine, Marijuana, Methamphetamine, Barbiturates, Benzodiazepines, Methylenedioxymethamphetamine, Methadone, Oxycodone, Phencyclidine and their metabolites ( specifically THC ) 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.
Here's a breakdown of the acceptance criteria and study information for the Rapid Single/Multi-drug Test Cup and Dipcard, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for precision or accuracy studies in a quantitative manner (e.g., "must achieve X% agreement"). However, given the nature of the data presented, the implied acceptance criterion for precision is that the device should reliably identify samples at or above the cutoff as positive, and samples significantly below the cutoff as negative, with a reasonable degree of accuracy for concentrations near the cutoff. For accuracy, the implied acceptance criterion is that the device should demonstrate high agreement with GC/MS analysis. For lay user readability, the implied criterion is high user comprehension.
Let's synthesize the data into a table based on these implied criteria.
Note on "Reported Device Performance": The document provides raw numbers of positive/negative results at different concentration levels for precision and individual count breakdowns for accuracy against GC/MS. To create a concise table, I will report the general trends and highlight key metrics. Specific percentages are primarily for the lay-user study.
| Acceptance Criteria Category | Specific Metric (Implied) | Reported Device Performance (Summary) |
|---|---|---|
| Precision (for each drug) | Reliable detection: |
- 0% false positives for negative samples
- 0% false negatives for high positive samples
- Consistent results at +/- 25% cutoff levels | Across all drugs and lots (single/multi-drug, cup/dipcard formats):
- Negative samples (0 ng/mL, -75% & -50% cutoff): Universally reported as 0 positive, 60 negative (100% accurate negative).
- High positive samples (+50%, +75%, +100% cutoff): Universally reported as 60 positive, 0 negative (100% accurate positive).
- Near Cutoff (-25% & +25% cutoff): Showed variability (e.g., AMP -25% cutoff ranged 4-10 positives out of 60, +25% cutoff ranged 50-58 positives out of 60). This variability near cutoff is expected for qualitative tests. |
| Accuracy (vs. GC/MS) | High agreement between device result and GC/MS for all concentration categories. Minimal discordant results. | For clinical specimens: - Drug free, less than half cutoff, and high positive: Generally 100% agreement with GC/MS.
- Near Cutoff Negative and Near Cutoff Positive: Showed some mixed results (expected for qualitative tests near cutoff).
- Discordant Results: A few specific cases reported where the device result (e.g., positive) did not match GC/MS (e.g., device positive for MET at 867ng/mL vs. 1000ng/mL cutoff, device negative for THC at 61ng/mL vs. 50ng/mL cutoff). These are mostly near the cutoff. |
| Interference | No interference from common substances found in urine at 100µg/mL. | None of the tested compounds (listing many common drugs and substances) were shown to interfere with the device's performance when added to drug-free or drug-positive urine. |
| pH Effect | Device performance unaffected by urinary pH range of 3 to 9. | The results demonstrated that varying ranges of pH (3 to 9 in 1 pH unit increments) do not interfere with the test's performance when spiked at 50% below and 50% above cutoff levels. |
| Specific Gravity Effect | Device performance unaffected by urinary specific gravity range (1.002-1.040). | The results demonstrated that varying ranges of urinary specific gravity (1.002, 1.010, 1.020, 1.030, 1.040) do not affect the test result when spiked at 50% below and 50% above cutoff. |
| Lay User Study | High agreement with expected results and high user comprehension for home use. | Agreement: For lay users, agreement percentages were high, generally 100% for clear negatives and clear positives, and ranging from 83% to 97% for samples near the +/- 25% cutoff for various drugs and test formats.
Readability/Ease of Use: 100% of users felt the test was easy to use and the instructions were easy to understand. The labeling was assessed at a 6th-grade reading level. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: 60 determinations per lot per concentration (Total: 9 concentrations * 60 determinations/lot * 3 lots = 1620 observations for each drug type). This was for both single drug and multi-drug formats, and both cup and dipcard.
- Data Provenance: Not explicitly stated, but based on the overall document, it is likely internal laboratory testing or conducted at the specified Point-of-Care sites, implying prospective. The "nonparticipant" blinding suggests a controlled, prospective design.
- Accuracy Study (Clinical Urine Specimens):
- Sample Size: 80 clinical urine specimens for each drug type. These were divided into five categories (drug free, less than half cutoff, near cutoff negative, near cutoff positive, high positive).
- Data Provenance: "Clinical urine specimens" suggests real-world samples. The study was conducted by nurses at two Point-of-Care sites, indicating prospective, real-world data collection using the device.
- Home Use Consumer Study:
- Sample Size: 360 lay users. Urine samples were prepared at various concentrations (0, +/- 50% cutoff, +/- 25% cutoff, +100% cutoff). Each participant performed 1 test on a provided specimen.
- Data Provenance: Prospective, controlled study with lay users using prepared samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Precision Study: Ground truth was established by spiking known concentrations of drugs into drug-free urine. The concentrations were "confirmed with GC/MS." No human experts were used for ground truth directly for precision.
- Accuracy Study (Clinical Urine Specimens): The ground truth for the clinical urine specimens was established by Gas Chromatography/Mass Spectrometry (GC/MS) analysis. This is an analytical chemistry technique, not human expert interpretation.
- Home Use Consumer Study: Ground truth was established by spiking known concentrations of drugs into drug-free urine. The concentrations were "confirmed with GC/MS." No human experts were used for ground truth directly for the lay user study's analytical performance.
4. Adjudication Method for the Test Set
- Precision Study: The samples were "blindly labeled by a nonparticipant" and "randomized prior to testing." Results were qualitative (Positive/Negative) based on the device's output. No explicit multi-reader adjudication method (e.g., 2+1) is mentioned; it appears to be a direct comparison of the device's qualitative result to the known spiked concentration.
- Accuracy Study (Clinical Urine Specimens): "All samples were blindly labeled by a nonparticipant" and "randomized prior to testing." The device results were compared directly to the GC/MS analysis. No multi-reader adjudication is mentioned for the device's interpretation or the GC/MS results.
- Home Use Consumer Study: Each participant performed one test and filled out a questionnaire. The device's qualitative result (positive/negative) from the lay user was compared against the known spiked concentration. No explicit multi-reader adjudication is mentioned.
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. This device is a qualitative in-vitro diagnostic (drug test cup/dipcard) that provides a direct positive or negative result, read by an individual (either a healthcare professional or a lay user). It is not an imaging AI device that assists human readers in interpreting complex medical images. Therefore, an MRMC comparative effectiveness study involving AI-assisted human readers is not applicable and was not performed.
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 qualitative test. Its performance (producing a positive or negative line) is inherent to the device's chemical assay. While a human physically observes the lines, the "algorithm" is the chemical reaction and visual indicator built into the device. The precision and accuracy studies directly reflect this standalone chemical "algorithm's" performance against known concentrations or GC/MS. The lay user study evaluated the human reading the standalone device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The primary ground truth used for evaluating the performance of the device was known spiked concentrations of drugs (confirmed by GC/MS) for precision and lay user studies, and Gas Chromatography/Mass Spectrometry (GC/MS) analysis for clinical accuracy studies. GC/MS is a highly accurate analytical method considered a gold standard for confirming the presence and concentration of drugs in urine.
8. The sample size for the training set
The document describes performance studies, but it does not mention a "training set" in the context of machine learning or AI models. This device is a lateral flow immunoassay, which does not typically involve training data in the AI sense. The design and validation of this type of device rely on analytical and clinical performance studies, not machine learning model training.
9. How the ground truth for the training set was established
As there is no mention of a "training set" for an AI or machine learning model, this question is not applicable to the information provided in the document. The ground truth for the performance evaluation (test sets) was established through spiking known drug concentrations into urine and confirmation via GC/MS, as detailed in point 7.
§ 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).