(373 days)
The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of Cannabinoids in neat human oral fluid, collected into the LZI Oral Fluid THC Collector, at the cut-off value of 4 ng/mL with △9- tetrahydrocannabinol (THC) as calibrators. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Oral Fluid Cannabinoids Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid Cannabinoids Enzyme Immunoassay at the cut-off value of 4 ng/mL.
The LZI Oral Fluid Cannabinoids Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid Cannabinoids Enzyme Immunoassay at the cut-off value of 4 ng/mL.
The LZI Oral Fluid Cannabinoids assay is a homogeneous enzyme immunoassay with ready-touse liquid reagent. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, cannabinoid derivative-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound cannabinoid derivative-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The Ri solution contains mouse monoclonal anti-Cannabinoids antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09%) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with Cannabinoids, stabilizers, in buffer with sodium azide (0.09%) as preservative.
The LZI Oral Fluid Cannabinoids Enzyme Immunoassay calibrators and controls designated for use at the 4 ng/mL cutoffs contain 0, 2, 3, 4, 5, 6, and 12 ng/mL of Δ'-tetrahydrocannabinol (THC) in synthetic oral fluid with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The provided text describes the LZI Oral Fluid Cannabinoids Enzyme Immunoassay, its acceptance criteria, and the studies performed to demonstrate its performance.
Here's the breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a separate section. However, the performance characteristics provided, particularly the "Method Comparison: Clinical Samples" and "Precision" data, implicitly define the expected performance for qualitative and semi-quantitative results against a confirmatory method (GC/MS).
Given the information, the acceptance criteria can be inferred as a high concordance between the immunoassay and the GC/MS reference method, especially for distinguishing between positive and negative samples around the 4 ng/mL cutoff. For specific values, the "Precision" tables show the expected ranges of positive/negative results at various concentrations relative to the cutoff.
Here's a table summarizing the reported device performance, inferring acceptance based on achieving high concordance:
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance (LZI Oral Fluid Cannabinoids Enzyme Immunoassay) |
|---|---|---|
| Qualitative Method Comparison | High concordance with GC/MS (confirmatory method) for positive and negative samples around the 4 ng/mL cutoff. | Total Agreement for Negative: 20 (immunosassay negative) vs 20 (GC/MS negative) |
| (Clinical Samples - 4 ng/mL Cutoff) | Total Agreement for Positive (High Positive): 35 (immunoassay positive) vs 35 (GC/MS high positive) | |
| Near Cutoff Agreement (Negative): 6 (immunoassay negative) vs 6 (GC/MS near cutoff negative) | ||
| Near Cutoff Agreement (Positive): 5 (immunoassay positive) vs 5 (GC/MS near cutoff positive) | ||
| Discrepancies: 2 GC/MS negative reported as EIA positive, 2 GC/MS positive reported as EIA negative (around cutoff) | ||
| Semi-Quantitative Method Comparison | High concordance with GC/MS (confirmatory method) for positive and negative samples around the 4 ng/mL cutoff. | Total Agreement for Negative: 20 (immunoassay negative) vs 20 (GC/MS negative) |
| (Clinical Samples - 4 ng/mL Cutoff) | Total Agreement for Positive (High Positive): 35 (immunoassay positive) vs 35 (GC/MS high positive) | |
| Near Cutoff Agreement (Negative): 7 (immunoassay negative) vs 7 (GC/MS near cutoff negative) | ||
| Near Cutoff Agreement (Positive): 6 (immunoassay positive) vs 6 (GC/MS near cutoff positive) | ||
| Discrepancies: 1 GC/MS negative reported as EIA positive, 1 GC/MS positive reported as EIA negative (around cutoff) | ||
| Qualitative Precision | Consistent results around the cutoff, with expected positive and negative classifications at concentrations well above and below the cutoff. | At 0.0 ng/mL to 3.0 ng/mL: 80/80 negative (100% agreement) |
| (Total Precision, 4 ng/mL Cutoff) | At 5.0 ng/mL to 8.0 ng/mL: 80/80 positive (100% agreement) | |
| At 4.0 ng/mL (cutoff): 59 Positive / 21 Negative (73.75% positive) | ||
| Semi-Quantitative Precision | Consistent results around the cutoff, with expected positive and negative classifications at concentrations well above and below the cutoff. | At 0.0 ng/mL to 3.0 ng/mL: 80/80 negative (100% agreement) |
| (Total Precision, 4 ng/mL Cutoff) | At 5.0 ng/mL to 8.0 ng/mL: 80/80 positive (100% agreement) | |
| At 4.0 ng/mL (cutoff): 54 Positive / 26 Negative (67.5% positive) |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Size: 42 positive and 41 negative unaltered oral fluid samples, totaling 83 samples.
- Data Provenance: Not explicitly stated regarding country of origin. The study appears to be retrospective as samples were collected and then evaluated. The samples were collected using the "LZI Oral Fluid Collector."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth was established by Gas or Liquid Chromatography/mass spectrometry (GC/MS or LC/MS), which is described as the "preferred confirmatory method." This is a laboratory analytical technique, not a human expert judgment. Therefore, the concept of "number of experts" is not applicable in this context.
4. Adjudication method for the test set:
- No adjudication method involving human experts is described since the ground truth was established by GC/MS. The immunoassay results were directly compared to the GC/MS quantitative values.
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, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay for drug detection, not an AI-assisted diagnostic tool that would typically involve human readers interpreting results.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone performance study was done. The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is an automated assay designed for use with clinical chemistry analyzers (e.g., Beckman AU400e). Its performance (precision, method comparison) was evaluated directly as the algorithm/assay only, without human interpretation factored into the core performance metrics presented. While a human might interpret the final positive/negative result, the performance data itself is of the device in isolation.
7. The type of ground truth used:
- The ground truth used was analytical confirmation by Gas Chromatography/Mass Spectrometry (GC/MS). This is a highly specific and sensitive laboratory method considered the "gold standard" for confirming drug presence and concentration.
8. The sample size for the training set:
- The document does not provide information on a training set size. The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is a chemical assay (enzyme immunoassay), not a machine learning or AI algorithm that typically requires a distinct training dataset. Its development would involve chemical optimization and characterization rather than algorithm training.
9. How the ground truth for the training set was established:
- As there's no explicit mention of a training set in the context of an AI/ML algorithm, this question is not applicable in the same way it would be for an AI device. The "ground truth" for developing such an assay would involve known concentrations of target analytes and cross-reactants to characterize the assay's chemical behavior.
§ 862.3870 Cannabinoid test system.
(a)
Identification. A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds includedelta -9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.(b)
Classification. Class II (special controls). A cannabinoid 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).