(104 days)
The ATTEST Drug Screen Cup and the ATTEST Drug Screen Dip Card are rapid lateral flow immunoassays for the qualitative detection of 6-Acetylmorphine, d-Amphetamine, Benzoylecgonine, EDDP, d/1-Methadone, d-Methamphetamine, d/Methylenedioxymethamphetamine, Nortriptyline, Oxazepam, Oxycodone, Phencyclidine, d-Propoxyphene, Secobarbital and THC-COOH in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:
| Analyte | Calibrator | Cutoff (ng/mL) |
|---|---|---|
| 6-Acetylmorphine | 6-monoacetylmorphine | 10 |
| Amphetamine | d-Amphetamine | 500 |
| Amphetamine | d-Amphetamine | 1,000 |
| Secobarbital | Secobarbital | 300 |
| Oxazepam | Oxazepam | 300 |
| Buprenorphine | Buprenorphine | 10 |
| EDDP | 2-ethylidene-1,5-dimethyl-3-3- diphenylpyrrolidine | 300 |
| Cocaine | Benzoylecgonine | 150 |
| Cocaine | Benzoylecgonine | 300 |
| Ecstasy | d,l-Methylenedioxymethamphetamine | 500 |
| Methamphetamine | d-Methamphetamine | 500 |
| Methamphetamine | d-Methamphetamine | 1,000 |
| Marijuana | 11-nor-Δ9-THC-9-COOH | 20 |
| Marijuana | 11-nor-Δ9-THC-9-COOH | 50 |
| Methadone | d/l-Methadone | 300 |
| Opiates | Morphine | 300 |
| Opiates | Morphine | 2,000 |
| Oxycodone | Oxycodone | 100 |
| Phencyclidine | Phencyclidine | 25 |
| Propoxyphene | Propoxyphene | 300 |
| Nortriptyline | Nortriptyline | 1,000 |
The single or multi-test panels can consist of the above listed analytes in any combination, up to a maximum of 16 analytes, with and without on-board adulteration/specimen validity tests (SVT) in the cup format. The drug screen tests are intended for prescription use only.
The tests provide only a preliminary result. To obtained a confirmed analytical result, a more specific alternative chemical method should be used. Gas Chromatography / Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.
For prescription use, the devices consist of:
- a. 10 or 25 test cups or dip cards with or without adulteration/specimen validity tests
- b. Package Insert
- c. Procedure Card
Here's a breakdown of the acceptance criteria and study details for the ATTEST Drug Screen Cup and Dip Card, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate, quantitative target for each metric before presenting the results. Instead, it presents the performance data and implies that these results demonstrate the device's suitability. The primary performance metric presented is agreement with gold-standard methods (GC/MS, LC/MS or equivalent), and for most categories, the reported agreement is 100% or very close to it.
For the purpose of this analysis, I will infer the "acceptance criteria" from the reported performance, assuming that the FDA's acceptance is based on these high agreement rates, especially at or further from the cutoff concentrations.
| Characteristic | Acceptance Criteria (Inferred from data) | Reported Device Performance (Agreement with Gold Standard) - ATTEST Cup & Dip Card |
|---|---|---|
| Precision/Reproducibility | >99% correlation at +/-50% of each assay cutoff across multiple sites. | >99% correlation (across Advin Biotech and 3 external sites). |
| Analytical Specificity | No or minimal cross-reactivity for structurally similar compounds; no positive interference from chemically dissimilar compounds, endogenous agents, or pH/specific gravity variations. | Detailed tables provided showing specific cross-reactivity percentages (e.g., d-Amphetamine 100%, l-Amphetamine 1%), and non-interference for numerous substances, pH (4-9), and specific gravity (1.003-1.030). |
| Method Comparison/Accuracy | High agreement with gold-standard methods (GC/MS, LC/MS) across drug-free, near-cutoff, and beyond-cutoff concentrations. | Generally 93.2% - 100% agreement for negative and positive results, with specific discordant cases identified and quantified relative to the cutoff. |
| Read Time Stability | Stable results expected for a reasonable reading window (e.g., up to 75 minutes). | Test results stable for up to 75 minutes. |
2. Sample Size Used for the Test Set and Data Provenance
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Sample Size for Test Set: The method comparison/accuracy study (which serves as the "test set" for performance evaluation) uses the following sample sizes per drug test/cutoff combination:
- Drug-free: 40 samples
- -50% C/O to +25% C/O to +50% C/O: Varies (e.g., 4 for 6-AM/10, 5 for THC/20)
- >+50% C/O: Varies (e.g., 35 for 6-AM/10, 46 for THC/20)
- Total samples per drug test/cutoff category appears to be around 80-100 samples.
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Data Provenance: The document states that the studies used "clinical urine specimens previously quantitated for the target drugs of abuse by gold-standard methods (GC/MS, LC/MS or equivalent)." There is no explicit mention of the country of origin for these clinical specimens or if they were retrospective or prospective. Given the context of a 510(k) submission, these are typically retrospective studies using archived, de-identified clinical samples.
3. Number of Experts Used to Establish the Ground Truth and Qualifications
- The document does not mention the use of human experts to establish the ground truth for the test set.
- Ground truth for the method comparison/accuracy study was established by "gold-standard methods (GC/MS, LC/MS or equivalent)", which are analytical laboratory techniques, not expert human interpretation.
4. Adjudication Method for the Test Set
- Since the ground truth was established by instrumental analytical methods (GC/MS, LC/MS), there was no human adjudication (e.g., 2+1, 3+1) involved in determining the "true" presence or absence of drugs for the test set. The results from the gold-standard methods served as the definitive determination.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. The ATTEST Drug Screen Cup and Dip Card are qualitative lateral flow immunoassays and function as standalone diagnostic devices. Their performance is evaluated against chemical reference methods, not against human readers. Therefore, the concept of "effect size of how much human readers improve with AI vs without AI assistance" is not applicable.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
- Yes, a standalone performance evaluation was done. The ATTEST Drug Screen Cup and Dip Card are designed to be used as standalone qualitative tests. The performance data presented (precision, analytical specificity, and method comparison/accuracy tables) directly reflect the device's diagnostic capability without human in-the-loop interaction for result interpretation, beyond simply reading a positive or negative line visually as designed by a qualitative immunoassay. The results are based on the device's output (presence or absence of control/test lines).
7. Type of Ground Truth Used
- The ground truth used was analytical gold-standard methods: Gas Chromatography / Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS), and their tandem mass-spectrometer versions. The document explicitly states these are the "preferred confirmatory methods."
8. Sample Size for the Training Set
- The document does not specify the sample size used for the training set. As this device is a rapid lateral flow immunoassay (a chemical test, not an AI/machine learning algorithm), the concept of a "training set" in the context of predictive modeling is not directly applicable in the same way. The device's components and antibodies are developed and optimized through laboratory work and validation, rather than "training" on a large dataset of results in the way an AI algorithm would be.
9. How the Ground Truth for the Training Set Was Established
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Given that this is a chemical immunoassay, the concept of a "training set" for ground truth establishment, as it pertains to AI/machine learning, is not directly relevant. The "ground truth" during the development and optimization of such assays would involve:
- Known concentrations of target analytes and potential cross-reactants: Used to optimize antibody binding, cutoff concentrations, and minimize false positives/negatives.
- Control samples: Including negative urine samples (drug-free) and positive urine samples spiked with known drug concentrations.
- Reference materials: Calibrators and controls with established values, often verified by GC/MS or LC/MS.
The "precision/reproducibility" and "analytical specificity" studies described in the document reflect parts of the characterization and validation process that would inform the final design and performance claims of the device.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).