(128 days)
The INSTANT-VIEW plus Multi-Drug of Abuse Urine Test - Simple Cup (OTC Use) device is a rapid, qualitative immunoassay device for the detection of one or more drugs or metabolites at the designated cutoff concentrations in human urine. The device can detect up to 13 drugs or their metabolites: Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Methamphetamine, Methadone, Phencyclidine, Tricyclic Antidepressants, Cannabinoids, MDMA, Morphine, Oxycodone. These assays may yield positive results when barbiturates, benzodiazepines, or tricyclic antidepressants are ingested at or above therapeutic doses. There are no uniformly recognized cutoff levels for barbiturates, benzodiazepines, or tricyclic antidepressants in urine. The assays are not intended to distinguish between prescription use or abuse of these drugs. This device provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Chromatography/mass spectrometry 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 obtained.
The INSTANT-VIEW plus Multi-Drug Urine Test - Simple Cup (Prescription Use) device is a rapid, qualitative immunoassay device for the detection of one or more drugs or metabolites at the designated cutoff concentrations in human urine. The device can detect up to 13 drugs or their metabolites: Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Methamphetamine, Methadone, Phencyclidine, Tricyclic Antidepressants, Cannabinoids, MDMA, Morphine, Oxycodone. These assays may yield positive results when barbiturates, benzodiazenines, or tricyclic antidepressants are ingested at or above therapeutic doses. There are no uniformly recognized cutoff levels for barbiturates, benzodiazepines, or tricyclic antidepressants in urine. The assays are not intended to distinguish between prescription use or abuse of these drugs. This device provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Chromatography/mass spectrometry 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 obtained.
These devices are one-step lateral flow chromatographic immunoassays consisting of any combination of one (1) to thirteen (13) individual test strip(s). Each test strip in the device consists of 1) a conjugate pad containing colloidal gold coupled with the anti-drug antibodies and 2) nitrocellulose membrane containing a test line (T line) coated with the conjugated drug antigen and a control line (C line). The C line serves as an internal quality control of the system and appears as a burgundy-colored band during the test regardless of the presence of the drug.
Here's an analysis of the acceptance criteria and study detailed in the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes two types of performance studies: a "precision" study (analytical performance) and a "lay user study" (user performance for OTC use). The acceptance criteria for the precision study appear to be implicit in the results, suggesting that all negative samples below a certain threshold should be negative, and all positive samples above a certain threshold should be positive. For the lay user study, the acceptance criteria are for the interpretation of results by the lay users, implicitly aiming for high agreement with the expected result.
Analytical Performance (Precision Study - Example for Amphetamines)
| Analyte | Concentration (ng/mL) | % of Cutoff | Expected Result | Reported Results (Neg/Pos) Lot 1 | Reported Results (Neg/Pos) Lot 2 | Reported Results (Neg/Pos) Lot 3 | Acceptance Criteria (Implicit) |
|---|---|---|---|---|---|---|---|
| Amphetamines | 0 | 0% | Negative | 50/0 | 50/0 | 50/0 | 100% negative |
| 250 | -75% | Negative | 50/0 | 50/0 | 50/0 | 100% negative | |
| 500 | -50% | Negative | 50/0 | 50/0 | 50/0 | 100% negative | |
| 750 | -25% | Negative | 50/0 | 50/0 | 50/0 | 100% negative | |
| 1000 | Cutoff | Mixed/Transition | 2/48 | 1/49 | 1/49 | Expected to show a transition from negative to positive results, with some variability around the cutoff. | |
| 1250 | +25% | Positive | 0/50 | 0/50 | 0/50 | 100% positive | |
| 1500 | +50% | Positive | 0/50 | 0/50 | 0/50 | 100% positive | |
| 1750 | +75% | Positive | 0/50 | 0/50 | 0/50 | 100% positive | |
| 2000 | +100% | Positive | 0/50 | 0/50 | 0/50 | 100% positive | |
| Summary of performance from table for analytes (e.g. Amphetamines): For concentrations at or below -25% of cutoff, all results were negative (150/0 across 3 lots). For concentrations at or above +25% of cutoff, all results were positive (150/0 across 3 lots). At the cutoff point (1000 ng/mL), a mix of negative and positive results were observed across the three lots (e.g., Lot 1: 2 negative, 48 positive), indicating sensitivity around the cutoff as expected for a qualitative assay. |
Lay User Study Performance (Example for Amphetamines)
| Drug | Concentration (ng/ml) | Expected Result | Number of samples | Reported Negative | Reported Positive | Acceptance Criteria (Implicit) |
|---|---|---|---|---|---|---|
| AMP (1000) | 0 | Negative | 350 | 350 | 0 | High accuracy (e.g., >95%) in interpretation for clearly negative samples. |
| 750 (75%) | Negative | 10 | 9 | 1 | High accuracy in interpretation for samples below cutoff. A small number of false positives might be acceptable, but ideally none. | |
| 1250 (125%) | Positive | 10 | 1 | 9 | High accuracy in interpretation for samples above cutoff. A small number of false negatives might be acceptable, but ideally none. | |
| 1500 (150%) | Positive | 30 | 0 | 30 | High accuracy in interpretation for clearly positive samples. | |
| Summary of performance from table for AMP: For 0% concentration, 100% negative results (350/350). For 75% concentration, 90% negative (9/10). For 125% concentration, 90% positive (9/10). For 150% concentration, 100% positive (30/30). This generally indicates accurate interpretation by lay users. | ||||||
| Surveys and labeling assessments: For all categories (intended use, directions for test, performing test, interpreting results), a very high percentage of participants rated the ease of understanding as "very easy to understand" or "easy to understand" (96.5% to 100%). This suggests the labeling and instructions were clear for lay users. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Analytical/Precision Study Test Set:
- For each of the 13 analytes, there were 9 different concentration levels tested.
- For each concentration level, 50 samples were tested per Lot (Neg/Pos).
- There were 3 Lots, for a total of 150 tests per concentration level per analyte.
- Total tests per analyte: 9 concentrations * 50 samples/conc/lot * 3 lots = 1350 tests.
- Total tests across all 13 analytes: 1350 tests/analyte * 13 analytes = 17,550 tests.
- Data Provenance: Not explicitly stated, but typically these types of precision studies are conducted in a controlled laboratory setting (e.g., by the manufacturer). It is a retrospective analysis of device performance under controlled conditions.
-
Lay User Study Test Set:
- For each analyte, various concentrations at 0%, 75%, 125%, and 150% of the cutoff were tested.
- The number of samples varied per concentration level per analyte. For example, for Amphetamines, there were 350 samples at 0%, 10 at 75%, 10 at 125%, and 30 at 150%. This totals 400 samples for Amphetamines.
- Since there were 13 analytes, this would suggest a very large number of total tests if each participant tested all analytes. However, the text states "each participant was provided one (1) package insert, one (1) blind labeled test solution, and one (1) test device. Test solutions were randomly picked for participants, one for each." This implies each participant (total 400) tested one specific drug concentration. Therefore, the overall sample size for the lay user study is 400 participants/tests.
- Data Provenance: The study was conducted with 400 human participants with "diverse educational backgrounds and ranged in age from 18 to >60." This is prospective data collection with human subjects. The country of origin is not explicitly stated, but given it's an FDA submission, it's typically in the US or in a country following similar regulatory standards.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Analytical/Precision Study: The ground truth for the test concentrations (e.g., 0 ng/mL, 250 ng/mL, cutoff, etc.) is established by laboratory standards and precise dilution methods, not by human experts. The concentrations were precisely prepared.
- Lay User Study: Similar to the analytical study, the ground truth for these samples was based on the known, prepared concentrations of the drug within the test solutions. No human experts were used to establish the ground truth; it was based on the controlled spiking of urine samples.
4. Adjudication Method for the Test Set
- Analytical/Precision Study: No adjudication method involving multiple readers is mentioned. The results were recorded as Neg/Pos based on the device's output and presumably read by the operators performing the tests.
- Lay User Study: No formal adjudication method is mentioned. Each participant performed one test and reported their result. The study assessed how well the individual lay users interpreted the result, rather than having multiple readers interpret the same result for adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This device is a rapid, qualitative immunoassay for drug detection, and the studies performed focus on its analytical performance and lay user interpretability, not on reader improvement with AI assistance. The device itself is not an AI-assisted diagnostic tool for human readers.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- This device is not an AI algorithm. It is a chemical immunoassay device. The results are visually read by a human. Therefore, a "standalone" algorithmic performance study without human-in-the-loop is not applicable in the context of AI. However, the "precision study" can be considered a standalone performance assessment of the device's chemical reactions, irrespective of user interpretation (though a human still reads the lines).
7. Type of Ground Truth Used
- Analytical/Precision Study: The ground truth was based on known, precisely prepared drug concentrations in the urine matrix. This is a form of "spiked" samples, where the true concentration is known by the experimenters.
- Lay User Study: The ground truth was also based on known, precisely prepared drug concentrations in the test solutions given to participants.
8. Sample Size for the Training Set
- This device is not an AI/ML algorithm that requires a training set. It is a chemical immunoassay. Therefore, the concept of a "training set" is not applicable.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as 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).