(58 days)
Hightop® Multi-Drug Urine Test Cup tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethy1-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:
| Drug (Identifier) | Cut-off level |
|---|---|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Secobarbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethy1-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |
Hightop® Multi-Drug Urine Test Cup offers any combinations from 2 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for OTC use.
The tests may vield positive results for the prescription drugs Buprenorphine, Oxazepam, Secobarbital, Propoxyphene, and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.
The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.
Hightop® Multi-Drug Urine Test Cup Rx tests are competitive binding. lateral flow immunochromatographic assavs for qualitative and simultaneous detection of Amphetamine, Secobarbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:
| Drug (Identifier) | Cut-off level |
|---|---|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Secobarbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Cannabinoids (THC) | 50 ng/mL |
Hightop® Multi-Drug Urine Test Cup Rx offers any combinations from 2 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for prescription use.
The tests may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Secobarbital, Propoxyphene, and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.
The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.
The Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx are rapid, single-use in vitro diagnostic devices. Each test kit contains a test device in one pouch. One pouch contains a test Hightop® Cup and two desiccants, and a package insert. The Hightop® Multi-Drug Urine Test Cup is intended for over-the-counter use and the Hightop® Multi-Drug Urine Test Cup Rx is intended for prescription use.
The provided document describes the performance characteristics and studies for the Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx. This device is an in-vitro diagnostic test.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
For an in vitro diagnostic device like this multi-drug urine test cup, the "acceptance criteria" generally refers to the expected outcomes and performance targets for sensitivity and specificity around the defined cut-off concentrations, as demonstrated by the precision and method comparison studies. The reported device performance is indicated by the agreement of the device results with LC/MS (Liquid Chromatography/Mass Spectrometry) reference results.
The precision study results show the device performance across various concentrations relative to the cutoff, aiming for all negative results below the -25% cutoff and all positive results above the +25% cutoff. The "Near Cutoff Negative" and "Near Cutoff Positive" categories show deviations which are commonly observed for immunoassay devices operating close to the clinical cutoff.
A summarized table of the stated performance for each drug at various concentrations relative to the cutoff is presented in the original document (e.g., page 11). For the purpose of this summary, a general acceptance criterion for qualitative drug screening tests is typically high agreement with a reference method, especially for samples outside the +/- 25% cutoff range, and reasonable agreement within the +/- 25% cutoff range, as these regions represent the limits of detection and decision points for such assays. The acceptance is implicitly demonstrated by the results showing high concordance for samples sufficiently above or below the cutoff.
Here is a summary of the precision data for Buprenorphine (BUP 10) as an example. Similar tables exist for each drug on pages 11-15.
Acceptance Criteria (Implicitly based on performance expectations for qualitative drug screens) and Reported Device Performance (Precision Study for BUP 10)
| Concentration by LC/MS (ng/mL) (Relative to 10 ng/mL Cutoff) | Acceptance Criteria (Expected Result) | Reported Performance (Lot I, total 40 tests) | Reported Performance (Lot II, total 40 tests) | Reported Performance (Lot III, total 40 tests) |
|---|---|---|---|---|
| Positive Samples | ||||
| +100% cutoff (20.639) | All Positive (40+) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) |
| +75% cutoff (18.961) | All Positive (40+) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) |
| +50% cutoff (16.144) | All Positive (40+) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) |
| +25% cutoff (12.894) | Mostly Positive | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) | 0-/40+ (100% Positive) |
| Cutoff (10.931) | Mix of Positive/Negative (as expected at cutoff) | 12-/28+ (70% Positive) | 11-/29+ (72.5% Positive) | 13-/27+ (67.5% Positive) |
| Negative Samples | ||||
| -25% cutoff (7.847) | Mostly Negative | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) |
| -50% cutoff (4.699) | All Negative (40-) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) |
| -75% cutoff (2.372) | All Negative (40-) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) |
| -100% cutoff (0) | All Negative (40-) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) | 40-/0+ (100% Negative) |
| Note: A result of "0-/40+" means 0 negative results and 40 positive results. "40-/0+" means 40 negative results and 0 positive results. "12-/28+" means 12 negative results and 28 positive results. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Sample Size for Analytical Studies (Precision, Specificity, Interference, pH/SG effect): For each drug and each concentration point (-100%, -75%, -50%, -25%, cutoff, +25%, +50%, +75%, +100% cutoff), tests were performed two runs per day for 20 days using three lots of test Cups. This means for each concentration point, there were 2 runs/day * 20 days * 3 lots = 120 tests. For each drug, across the 9 concentration points reported in the precision studies, there were 9 * 40 * 3 = 1080 tests (40 tests per lot). For interference and specificity: results are reported for relevant concentrations.
- Sample Size for Method Comparison Studies: For each drug, 80 unaltered urine samples were used (40 negative and 40 positive). These 80 samples were tested by three operators.
- Sample Size for Lay-User Study:
- Configuration 1 (AMP 500, MET 500, MOP 300, COC 150): 140 participants (72 males, 68 females). Each participant presumably tested all drugs in this configuration. The results are presented for 20 samples per concentration level for each drug.
- Configuration 2 (AMP 1000, MET 1000, OPI 2000, COC 300): 140 participants (71 males, 69 females). Each participant presumably tested all drugs in this configuration. The results are presented for 20 samples per concentration level for each drug.
- Data Provenance: The analytical and method comparison studies were performed "in-house" and involved spiking drugs into "drug-free urine samples" and "unaltered urine samples." The lay-user study involved recruitment from "three sites." The exact country of origin for the samples or study sites is not explicitly stated, but the manufacturer is Qingdao HIGHTOP Biotech Co., Ltd. in China, suggesting the studies likely took place in China or were managed by the Chinese manufacturer. The studies are retrospective in the sense that samples were prepared or collected and then blinded and tested.
3. Number of Experts and Qualifications for Ground Truth
- Analytical and Method Comparison Studies: LC/MS (Liquid Chromatography/Mass Spectrometry) was used to confirm the concentrations of drugs in the urine samples. This is an objective, highly accurate, and quantitative chemical method. The document does not specify the number of experts or their qualifications for performing the LC/MS analysis, but LC/MS is a standard laboratory method typically performed by trained laboratory technicians or chemists.
4. Adjudication Method for the Test Set
- Analytical and Method Comparison Studies: The ground truth for these studies was established by LC/MS results. There is no mention of human expert adjudication in the traditional sense (e.g., 2+1, 3+1 consensus). The device's qualitative results (positive/negative) were directly compared against the quantitative LC/MS results relative to the defined cutoff concentration.
- Lay-User Study: Outcomes were reported as percentage of correct results compared to the known spiked concentrations. No explicit human adjudication method beyond comparing the lay users' interpretations to the true spiked concentrations is mentioned.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described in the traditional sense of comparing human readers' performance with and without AI assistance for image analysis or similar tasks.
- The document describes a "Lay-user study" which involves multiple users (readers) interpreting the device results, but this is a study to assess the ease of use and interpretation by non-professional users. It compares device performance (as interpreted by lay users) to LC/MS ground truth, not the improvement of human readers with AI assistance.
6. If a Standalone Study (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, the device itself is a standalone qualitative immunoassay device. Its performance, as reported in the "Precision" and "Method Comparison" sections (pages 11-15 and 25-35), represents the algorithm's (test strip's) performance in detecting drugs in urine samples without human interpretive bias (beyond the operator physically performing the test and reading the line, which is standard for such devices). The "Discordant Results" tables (pages 25-35) directly compare the device's output against the LC/MS reference.
7. The Type of Ground Truth Used
- LC/MS or LC/MS: For all analytical performance and method comparison studies (precision, specificity, interference, pH/SG effect, and comparison with operators), the ground truth for drug concentration was established by Liquid Chromatography/Mass Spectrometry (LC/MS) or LC/MS. This is a highly accurate and quantitative analytical method used as the gold standard for confirming drug concentrations.
- Known Spiked Concentrations: For the lay-user study, the ground truth was based on urine samples prepared with known, spiked concentrations of drugs into drug-free urine, which were then confirmed by LC/MS.
8. The Sample Size for the Training Set
- The document does not explicitly mention a training set in the context of an algorithm or AI model development. This device is a lateral flow immunochromatographic assay, which is a biochemical test, not a software algorithm that requires a "training set" in the machine learning sense. The performance studies described (precision, specificity, method comparison, lay-user study) are all validation studies.
9. How the Ground Truth for the Training Set was Established
- As there is no mention of a traditional "training set" for an algorithm, this question is not directly applicable. The device's performance is based on its inherent biochemical properties and design, which are then validated through the studies described using LC/MS as the ground truth for drug concentrations.
§ 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).