(65 days)
Wisdiag 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-dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana 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 |
| Marijuana (THC) | 50 ng/mL |
Wisdiag 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.
Wisdiag Multi-Drug Urine Test Cup Rx tests are competitive binding, lateral flow immunochromatographic assays 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 |
Wisdiag 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 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.
The Wisdiag Multi-Drug Urine Test Cup and Wisdiag Multi-Drug Urine Test Cup Rx are rapid, singleuse in vitro diagnostic devices. Each test kit contains a test device in one pouch. One pouch contains a test Wisdiag Cup and two desiccants, and a package insert. The Wisdiag Multi-Drug Urine Test Cup is intended for over-the-counter use and the Wisdiag Multi-Drug Urine Test Cup Rx is intended for prescription use.
The document describes the performance characteristics of the Wisdiag Multi-Drug Urine Test Cup and Wisdiag Multi-Drug Urine Test Cup Rx. The device is a rapid, single-use in-vitro diagnostic test for qualitative drug detection in human urine.
Here's an analysis of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" through a numerical threshold for accuracy metrics (e.g., "sensitivity must be >95%"). However, the precision studies and comparative studies demonstrate the device's performance against defined cut-off values. The "acceptance" can be inferred from the consistently high percentages of correct results at various concentrations relative to the cutoff, and the successful classification of samples below and above the cutoff.
Here's a table summarizing the performance based on the precision study and lay-user study for each drug at its respective cutoff concentrations. The "Reported Device Performance" here refers to the percentage of correct results for samples at the cutoff or near the cutoff values, as these are the most critical for determining accuracy. For "acceptance criteria," the expectation is generally high accuracy around the cutoff.
Table 1: Acceptance Criteria (Inferred) and Reported Device Performance
| Drug (Identifier) | Cut-off Level | Inferred Acceptance Criteria (Precision Study) | Reported Device Performance (Precision Study - Cutoff) | Reported Device Performance (Lay-User Study - Cutoff / closest concentrations) |
|---|---|---|---|---|
| AMP 500 | 500 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive (≥95% correct classification at these points, and good differentiation at cutoff). | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-27 Negative / 23-27 Positive (e.g., Lot I: 23-/27+) | Configuration 1 (AMP 500): 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). (Percentages represent classification according to expected outcome relative to actual value, not test result matches LC/MS). |
| BUP 10 | 10 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-27 Negative / 23-27 Positive (e.g., Lot I: 23-/27+) | Configuration 1: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 90% correct for +25% cutoff (2/20 negative, 18/20 positive). |
| BAR 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-28 Negative / 22-28 Positive (e.g., Lot I: 23-/27+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| BZO 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 24-27 Negative / 23-26 Positive (e.g., Lot I: 24-/26+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| COC 150 | 150 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-28 Negative / 22-27 Positive (e.g., Lot I: 28-/22+) | Configuration 1: 90% correct for -25% cutoff (18/20 negative, 2/20 positive). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| EDDP 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 25-28 Negative / 22-25 Positive (e.g., Lot I: 25-/25+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| MET 500 | 500 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-26 Negative / 24-27 Positive (e.g., Lot I: 25-/25+) | Configuration 1: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| MDMA 500 | 500 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-25 Negative / 25-28 Positive (e.g., Lot I: 24-/26+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| MOP 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-26 Negative / 24-28 Positive (e.g., Lot I: 25-/25+) | Configuration 1: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| MTD 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-27 Negative / 23-28 Positive (e.g., Lot I: 24-/26+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| OXY 100 | 100 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-27 Negative / 23-27 Positive (e.g., Lot I: 27-/23+) | Configuration 1: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| PCP 25 | 25 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-26 Negative / 24-28 Positive (e.g., Lot I: 26-/24+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| PPX 300 | 300 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 25-28 Negative / 22-25 Positive (e.g., Lot I: 25-/25+) | Configuration 1: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| TCA 1000 | 1000 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 22-27 Negative / 23-28 Positive (e.g., Lot I: 27-/23+) | Configuration 1: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| THC 50 | 50 ng/mL | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-27 Negative / 23-27 Positive (e.g., Lot I: 23-/27+) | Configuration 1: 90% correct for -25% cutoff (18/20 negative, 2/20 positive). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| AMP 1000 | 1000 ng/mL (Config 2) | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 24-27 Negative / 23-26 Positive (e.g., Lot I: 25-/25+) | Configuration 2: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| COC 300 | 300 ng/mL (Config 2) | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 24-27 Negative / 23-26 Positive (e.g., Lot I: 27-/23+) | Configuration 2: 100% correct for -25% cutoff (20/20 negative). 95% correct for +25% cutoff (1/20 negative, 19/20 positive). |
| MET 1000 | 1000 ng/mL (Config 2) | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-26 Negative / 24-27 Positive (e.g., Lot I: 26-/24+) | Configuration 2: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
| OPI 2000 | 2000 ng/mL (Config 2) | Consistent classification of -25% Cutoff samples as negative and +25% Cutoff samples as positive. | Negative: 49-50/50, Positive: 0-1/50 for -25% cutoff. Negative: 0-1/50, Positive: 49-50/50 for +25% cutoff. At Cutoff: 23-27 Negative / 23-27 Positive (e.g., Lot I: 23-/27+) | Configuration 2: 95% correct for -25% cutoff (19/20 negative, 1/20 positive). 100% correct for +25% cutoff (0/20 negative, 20/20 positive). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Precision Studies (Analytical Performance):
- Sample Size: For each drug and each concentration point (-100%, -75%, -50%, -25%, cutoff, +25%, +50%, +75%, +100% cutoff), 50 tests were performed per lot across 3 lots (2 runs/day for 25 days). This means 3 lots x 50 tests = 150 tests per concentration per drug. With 9 concentration points, it is 1350 tests per drug. With 15 drugs, roughly 20,250 tests in total.
- Data Provenance: The samples were prepared by spiking target drugs into drug-free urine samples. Drug-free urine samples were used for the -100% cutoff. The document does not specify the country of origin of the "drug-free urine samples" or the location where the samples were collected. It is retrospective in the sense that samples were prepared in a lab setting rather than collected prospectively from patients.
-
Comparison Studies (Standalone Performance):
- Sample Size: For each drug, 80 unaltered urine samples (40 negative and 40 positive) were used. These were then tested by 3 operators.
- Data Provenance: "Unaltered urine samples" were used. The document does not specify the country of origin. This appears to be retrospective as the samples were pre-collected and blinded.
-
Lay-User Study:
- Sample Size: 280 participants were recruited.
- 140 participants (66 males, 74 females) for Configuration 1 (AMP 500, MET 500, MOP 300, COC 150, BAR 300, BZO 300, BUP 10, EDDP 300, MDMA 500, MTD 300, OXY 100, PCP 25, PPX 300, TCA 1000, THC 50).
- 140 participants (72 males, 68 females) for Configuration 2 (AMP 1000, MET 1000, OPI 2000 (MOP 2000), COC 300, BAR 300, BZO 300, BUP 10, EDDP 300, MDMA 500, MTD 300, OXY 100, PCP 25, PPX 300, TCA 1000, THC 50).
- Each participant tested "one blind labeled test solution, and one test device." The concentration points tested were -100%, +/-75%, +/-50%, +/-25% of the cutoff. Given there are 15 assays per cup, and 8 concentration points, and 20 tests per concentration point, this implies a total of 15 * 8 * 20 = 2400 individual assay results per configuration (which aligns roughly with 140 participants given each participant runs multiple assays/drugs).
- Data Provenance: Samples were "prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cutoff by spiking drug(s) into drug free-pooled urine specimens." It doesn't state the source of the "drug free-pooled urine specimens" or the country of origin. This is a retrospective study based on prepared samples.
- Sample Size: 280 participants were recruited.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Ground Truth Method: LC/MS or LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) was used to confirm sample concentrations and establish the ground truth for all studies (Precision, Comparison, Lay-User).
- Number/Qualifications of Experts: The document does not specify human experts for establishing ground truth. The LC/MS data is considered the analytical "gold standard" or ground truth for drug concentrations in urine.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- No human adjudication method is described. The ground truth in all studies is based on LC/MS results. The device results (positive/negative) are compared directly to the quantitative LC/MS measurements relative to the specified cutoff.
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
- There was no MRMC comparative effectiveness study involving human readers with/without AI assistance. The device is a lateral flow immunoassay intended for direct interpretation of visual lines, not an AI-assisted diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, standalone performance was done.
- Precision Studies: This directly assesses the device's ability to correctly classify samples based on LC/MS confirmed concentrations, without human interpretation variability being the primary focus. The results "-/+" notation at each concentration reflects the count of negative and positive results from the device, which are then compared to the known concentration.
- Comparison Studies: These studies explicitly compare the "Wisdiag Multi-Drug Urine Test Cup" results (interpreted by three operators) directly against LC/MS results. While operators are involved in reading, the intent is to show the device's inherent performance when read, validating its accuracy against the gold standard. The "discordant results" further confirm areas where the device's output (even if read by a human) deviates from clinical truth (LC/MS).
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- Analytical Ground Truth: LC/MS or LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) was used as the ground truth method to confirm the concentrations of all samples. This is a highly accurate and quantitative chemical analysis method.
8. The sample size for the training set
- This device is a lateral flow immunoassay, not a machine learning or AI algorithm. Therefore, there is no "training set" in the context of machine learning. The device's performance is determined by its inherent biochemical design (antigen-antibody reactions) and manufacturing consistency, not by learning from a dataset.
9. How the ground truth for the training set was established
- As stated in point 8, there is no "training set" for this type of device.
§ 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).