Search Results

For In Vitro Diagnostic Use.

The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay is an enzyme immunoassay with a cutoff of 50 ng/mL in neat oral fluid collected by Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of methamphetamine in human oral fluid with clinical analyzers. This assay is calibrated against d-methamphetamine.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.

The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay is an in-vitro test to detect the presence of methamphetamine in human oral fluid samples collected by Quantisal or Quantisal II Oral Fluid Collection Device.

The provided document describes the performance characteristics of the Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay for the detection of methamphetamine in human oral fluid. This is a medical device, and the data presented supports its substantial equivalence to a legally marketed predicate device (LZI Oral Fluid Methamphetamine Enzyme Immunoassay [K131652]).

The document details various studies, primarily focusing on analytical performance rather than diagnostic accuracy involving human subjects. Therefore, many of the typical acceptance criteria and study aspects for AI-powered diagnostic devices (e.g., expert consensus for ground truth, MRMC studies, human-in-the-loop performance) are not applicable here. This device performs a chemical analysis.

Here's an analysis based on the provided text, addressing the relevant points:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this type of in-vitro diagnostic device are generally defined by demonstrating analytical performance metrics such as precision, specificity, linearity, and stability, with results falling within acceptable ranges. Substantial equivalence is often shown by comparing these metrics to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance:

Since this is an in-vitro diagnostic device, the "acceptance criteria" are implied by the expected performance common for such assays, aiming for high agreement with confirmed methods and consistent results. The document states a design goal of ">95% agreement" for method comparison.

• 0-37.5 ng/mL: 100% Negative (60/60)
• 50 ng/mL (Cutoff): 26 Neg/34 Pos
• 62.5-100 ng/mL: 100% Positive (60/60)
  Quantisal II Pad A:
• 0-37.5 ng/mL: 100% Negative (60/60)
• 50 ng/mL (Cutoff): 34 Neg/26 Pos
• 62.5-100 ng/mL: 100% Positive (60/60)
  Quantisal II Pad B:
• 0-37.5 ng/mL: 100% Negative (60/60)
• 50 ng/mL (Cutoff): 31 Neg/29 Pos
• 62.5-100 ng/mL: 100% Positive (60/60) |
  | Precision (Semi-Quantitative) | Mean concentration values close to expected spiked concentrations, and consistent classification. | Quantisal: Mean concentrations generally close to spiked values (e.g., 50 ng/mL mean 50.2 ng/mL). Classification performance similar to qualitative.
  Quantisal II Pad A: Mean concentrations generally close to spiked values (e.g., 50 ng/mL mean 48.6 ng/mL). Classification performance similar to qualitative.
  Quantisal II Pad B: Mean concentrations generally close to spiked values (e.g., 50 ng/mL mean 49.0 ng/mL). Classification performance similar to qualitative. |
  | Specificity/Cross-Reactivity | Minimal to no cross-reactivity with structurally unrelated compounds; expected cross-reactivity with structurally similar compounds. | - Structurally Similar: Varies. High cross-reactivity with MDMA (90.9%), (±)-3,4-Methylenedioxyethylamphetamine (45.5%), PMMA (180.2%), and some with d,l-Methamphetamine (45.5%), l-Ephedrine (1.2%), Fenfluramine (1.0%), MDA (0.8%), Methylone (0.2%), PMA (1.5%), d-Pseudoephedrine (0.3%), l-Pseudoephedrine (0.1%), d-Amphetamine (0.6%), l-Methamphetamine (0.7%).
• Structurally Unrelated: No interference observed at tested high concentrations (Table 9 shows a wide range of compounds tested up to 40,000 ng/mL). |
  | Interference (Endogenous/Exogenous) | No interference from common endogenous or exogenous substances. | No interference observed for a wide range of endogenous (e.g., Albumin, Bilirubin, Hemoglobin, Salivary-alpha-amylase) and exogenous (e.g., Acetylsalicylic Acid, Caffeine, Alcohol, Mouthwash, Toothpaste) compounds at tested levels. |
  | Interference (pH) | Performance maintained across physiological pH range. | No interference observed across pH 3.0-11.0. |
  | Linearity/Recovery | Recovery percentage within an acceptable range (e.g., 90-110%) across the linear range. | Linear range confirmed for 20-200 ng/mL. Recovery percentages: Quantisal (93.9-107.9%), Quantisal II "A" (96.8-104.0%), Quantisal II "B" (96.2-109.2%). |
  | Methamphetamine Stability | Stability of analyte in collected samples over time under specified storage conditions. | Oral fluid samples stable for up to 12 months at 2°C - 8°C. Data for 10-day stability at ambient temperature (8°C - 25°C) referenced in previous submissions (K183048, K200801). |
  | Calibration Duration | Consistent performance over defined calibration interval. | Achieved acceptance criteria up to 10 days. Recommended frequency: 7 days. |
  | Method Comparison (Qualitative & Semi-Quantitative) | Agreement with confirmatory method (LC-MS/MS) greater than 95%. | Achieved 100% agreement (40/40) for both positive and negative results when compared to LC-MS/MS across all three collection devices (Quantisal, Quantisal II "A", Quantisal II "B"). The total samples tested were 80, partitioned into 40 positive and 40 negative categories by LC-MS/MS. |

2. Sample Size and Data Provenance:

• Precision Study: 60 determinations for each concentration level, replicating across 15 days, 2 runs/day, 2 collection devices/run (N=60 per conc.). An additional 20-day study on 3 reagent lots for repeatability.
  • Provenance: Not explicitly stated (e.g., country of origin). The study states "Drug free negative oral fluid was spiked," implying a controlled laboratory setting (prospective creation of samples).
• Specificity and Cross-Reactivity: Compounds spiked into drug-free pooled oral fluid.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Interference (Structurally Unrelated): Compounds spiked into drug-free oral fluid containing methamphetamine at ±25% of cutoff.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Interference (Endogenous/Exogenous): Spiking into drug-free oral fluid; "Additional orally used products were tested by collecting oral fluid... from volunteers after use of the substances."
  • Provenance: Mix of controlled laboratory (prospective creation) and possibly prospective volunteer studies.
• Interference (pH): Spiked samples at various pH levels.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Linearity/Recovery: Serially diluted spiked samples.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Methamphetamine Stability: Spiked samples stored over time.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Calibration Duration: Spiked samples tested over time.
  • Provenance: Controlled laboratory (prospective creation of samples).
• Method Comparison: 80 deidentified, unaltered clinical oral fluid samples collected by Quantisal II Oral Fluid Collection Devices.
  • Provenance: "Obtained from clinical research facilities," suggesting real-world clinical samples, likely retrospective. Country of origin not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This is an in-vitro diagnostic (IVD) device for chemical analysis, not an imaging AI or clinical decision support system that relies on human expert interpretation of complex clinical data. Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists, pathologists) is not directly applicable.

For the analytical studies performed, the "ground truth" is established very precisely through:

• Spiking concentrations: Known amounts of methamphetamine or other compounds are added to drug-free oral fluid. The exact concentration is the ground truth.
• LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry): This is a highly accurate and widely accepted gold-standard method for confirming drug presence and concentration in biological samples. The results from LC-MS/MS served as the "ground truth" for the method comparison study. The laboratory performing this analysis would follow strict protocols and be staffed by trained analytical chemists or toxicologists, but no "expert consensus" process among multiple human interpreters is involved as it would be for an image-based diagnosis.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable. Ground truth for an IVD drug test is established by precise chemical methods (spiking, LC-MS/MS), not through subjective human interpretation requiring adjudication.

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:

Not applicable. This is an automated enzyme immunoassay (chemical test), not an AI-powered diagnostic assist tool for human readers/interpreters. There are no human "readers" in the loop.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

The device (assay performed on a clinical analyzer) functions as a standalone test. Its performance is reported solely based on its analytical output against the chemically defined ground truth (spiked concentrations, LC-MS/MS).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth was established through:

• Known Spiked Concentrations: For precision, specificity, interference, linearity, stability, and calibration studies.
• Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): For the method comparison study, LC-MS/MS results served as the definitive ground truth for "deidentified, unaltered clinical oral fluid samples".

8. The sample size for the training set:

Not applicable. This device is an enzyme immunoassay, a biochemical assay, not a machine learning/AI model that requires a "training set" in the computational sense. Its "training" is inherent in the chemical reactions and calibration curves established by the manufacturer, validated through the performance studies described.

9. How the ground truth for the training set was established:

Not applicable, as there is no "training set" in the context of an AI/ML algorithm. The assay's analytical characteristics are determined through standard laboratory validation practices using materials with known characteristics (e.g., calibrated standards, spiked samples).

Ask a specific question about this device

The Psychemedics homogeneous enzyme immunoassay (HEIA) for amphetamines in hair is an enzyme immunoassay system for the preliminary qualitative detection of methamphetamine in human head and body hair using a methamphetamine calibrator at 3 ng methamphetamine/10 mg hair or 5 ng methamphetamine/10 mg hair for the purpose of identifying methamphetamine use, and for the preliminary qualitative detection of amphetamine in human head and body hair using an amphetamine calibrator at 3 ng amphetamine/10 mg hair for the purpose of identifying amphetamine use.

This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not for sale to anyone. The Psychemedics HEIA for amphetamines in hair provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) is the preferred confirmatory method.

The test consists of two parts; a pre-analytical hair treatment procedure (to extract amphetamines from the solid hair matrix to a measurable liquid matrix) and the screening assay, the Psychemedics Amphetamines HEIA. The screening portion of the test system is based on competition for antibody binding sites between drug in the measurable liquid matrix and drug-labeled recombinant glucose-6-phosphate dehydrogenase (G6PDH). As the antibody binds labeled G6PDH, enzyme activity decreases. In the presence of drug, enzyme activity increases in direct proportion to the drug concentration. Active enzyme reduces nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose 6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically.

The Psychemedics Amphetamines HEIA consists of reagents R1 (anti-methamphetamine monoclonal antibody with substrate) and R2 (methamphetamine labeled recombinant G6PDH) for the detection of methamphetamine, and reagents R1 (anti-amphetamine monoclonal antibody with substrate) and R2 (amphetamine labeled recombinant G6PDH) for the detection of amphetamine.

The provided document describes the performance of the Psychemedics Homogeneous Enzyme Immunoassay (HEIA) for Amphetamines in Hair. This device is an in vitro diagnostic device intended for preliminary qualitative detection of methamphetamine and amphetamine in human hair.

Here's an analysis of the acceptance criteria and study data:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria values (e.g., "sensitivity must be > X%", "specificity must be > Y%"). Instead, it presents precision data and comparison studies against a confirmatory method (LC/MS/MS) to demonstrate acceptable performance. The acceptance is implied by the robust precision and high agreement with the confirmatory method, as well as satisfactory performance with cosmetic treatments and lack of cross-reactivity/interference from other substances.

However, we can infer some criteria from the presented data. The device's performance is summarized in its ability to correctly classify samples as positive or negative compared to LC/MS/MS and its precision at various concentration levels.

Inferred Acceptance Criteria vs. Reported Performance:

• At -100%, -75%, -50%, -25% of cutoff: All 8 replicates per level were correctly identified as Negative.
• At +25%, +50%, +75%, +100% of cutoff: All 8 replicates per level were correctly identified as Positive. This indicates perfect intra-assay precision for the tested ranges. |
  | Precision (Inter-Assay) | Consistent classification (all negative below cutoff, all positive above cutoff) at various concentration levels (e.g., -100%, -75%, -50%, -25%, +25%, +50%, +75%, +100% relative to cutoff) over multiple runs/days. | Methamphetamine (3 ng/10 mg & 5 ng/10 mg calibrator), Amphetamine (3 ng/10 mg calibrator):
• At -100%, -75%, -50%, -25% of cutoff: All 80 replicates per level were correctly identified as Negative.
• At +25%, +50%, +75%, +100% of cutoff: All 80 replicates per level were correctly identified as Positive. This indicates perfect inter-assay precision for the tested ranges. |
  | Agreement with LC/MS/MS | High concordance between HEIA results (positive/negative) and LC/MS/MS results across the dynamic range, with minimal false positives or negatives, particularly near the cutoff. Acknowledgment and explanation of expected discordant samples due to washing protocols should be provided. | Methamphetamine (3 ng/10 mg calibrator):
• 53 samples negative by HEIA were 4.50 ng/10 mg by LC/MS/MS.
• 5 negative HEIA samples were between 1.5-2.99 ng/10 mg by LC/MS/MS (near cutoff).
  -> Overall: High agreement. Discordant results (2 samples) were explained by the washing protocol for LC/MS/MS that is not applied to initial HEIA screening, leading to lower LC/MS/MS values after washing.
  Methamphetamine (5 ng/10 mg calibrator):
• 45 samples negative by HEIA were 7.50 ng/10 mg by LC/MS/MS.
• 4 negative HEIA samples were between 2.5-4.99 ng/10 mg by LC/MS/MS (near cutoff).
  -> Overall: High agreement. Discordant results (2 samples) were explained by the washing protocol.
  Amphetamine (3 ng/10 mg calibrator):
• 42 samples negative by HEIA were 4.50 ng/10 mg by LC/MS/MS.
• 6 negative HEIA samples were between 1.5-2.99 ng/10 mg by LC/MS/MS (near cutoff).
  -> Overall: High agreement. Discordant results (2 samples) were explained by the washing protocol. |
  | Cross-Reactivity | Limited significant cross-reactivity with common structurally similar compounds and no cross-reactivity with a wide range of other tested compounds at specified cutoffs. | Methamphetamine Assays (3 ng/10 mg & 5 ng/10 mg calibrators):
• MDMA, Para-Methoxy Methamphetamine, 1R, 2S Ephedrine, and MDEA showed some cross-reactivity (81-10% at 3 ng/10 mg; 83-10% at 5 ng/10 mg) requiring higher concentrations to be equivalent to the cutoff.
• R-Methamphetamine showed low cross-reactivity (2%).
• D-Amphetamine, L-Amphetamine, and MDA showed Overall: Cosmetic treatments did not affect the results. |
  | Sample Shipping Stability| Samples should remain stable (positive remain positive) after typical storage and shipping conditions for a reasonable period. | - 9 methamphetamine-positive samples remained positive for approximately 8 months after storage and two coast-to-coast shipments.
• 9 amphetamine-positive samples remained positive for approximately 6 months after storage and two coast-to-coast shipments.
  -> Overall: Demonstrated sufficient stability. |
  | Recovery | Sufficient recovery of the target analytes during the extraction procedure. | - Recovery of methamphetamine in the phosphate buffer extraction was approximately 100% complete after 3 hours.
• Recovery of amphetamine in the phosphate buffer extraction was approximately 100% complete after 3 hours.
  -> Overall: Satisfactory recovery. |

2. Sample Sizes and Data Provenance for the Test Set

The device uses multiple test sets for different aspects of its performance evaluation:

• Precision Studies:

  • Methamphetamine (3 ng/10 mg calibrator): 8 replicates per level (intra-assay) and 80 replicates per level (inter-assay) for a total of 8 levels (4 negative, 4 positive).
    • Intra-assay: 8 samples/level * 8 levels = 64 samples.
    • Inter-assay: 80 samples/level * 8 levels = 640 samples.
  • Methamphetamine (5 ng/10 mg calibrator): Same as above (64 intra-assay, 640 inter-assay samples).
  • Amphetamine (3 ng/10 mg calibrator): Same as above (64 intra-assay, 640 inter-assay samples).
  • Data Provenance: Spiked negative hair samples with LC/MS/MS validated calibrator and control solutions. This suggests controlled laboratory samples. No specific country of origin is mentioned, but "workplace setting" is mentioned for the comparison studies.

• Comparison Studies (HEIA vs. LC/MS/MS):

  • Methamphetamine (3 ng/10 mg calibrator): 114 individual hair samples. 58 negative and 56 positive initially identified by the test device.
  • Methamphetamine (5 ng/10 mg calibrator): 94 individual hair samples. 49 negative and 45 positive initially identified by the test device.
  • Amphetamine (3 ng/10 mg calibrator): 96 individual hair samples. 48 negative and 48 positive initially identified by the test device.
  • Data Provenance: Hair samples collected anonymously from a "workplace setting." These appear to be retrospective real-world samples. The document does not specify a country of origin.

• Cross-Reactivity & Interference Studies: Not specified, but likely involved a series of controlled laboratory experiments using specific concentrations of the compounds.

• Cosmetic Treatment Studies:

  • Methamphetamine: 5 methamphetamine-negative head hair samples, 4 methamphetamine-positive head hair samples.
  • Amphetamine: 9 amphetamine-negative head hair samples, 4 amphetamine-positive head hair samples.
  • Data Provenance: Not explicitly stated but likely controlled laboratory experiments using human hair.

• Sample Shipping Stability: 9 methamphetamine-positive samples, 9 amphetamine-positive samples.

• Recovery: Not specified, likely laboratory experiments.

3. Number of Experts and Qualifications for Ground Truth

The document does not describe the use of human experts to establish ground truth in the traditional sense of image interpretation or clinical diagnosis. The ground truth for this device is based on analytical chemistry results.

• Ground Truth Establishment: The ground truth for the comparison studies is established using Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS), which is the "preferred confirmatory method" for drug testing in hair. This is an objective chemical analysis method, not reliant on expert interpretation of observational data.

4. Adjudication Method for the Test Set

No adjudication method (like 2+1 or 3+1 consensus) is applicable or mentioned. The ground truth is established by a quantitative chemical analysis (LC/MS/MS). Discrepancies between the HEIA and LC/MS/MS results are analyzed and explained by the difference in sample preparation (washing for LC/MS/MS, no washing for HEIA screening), rather than resolved by expert consensus.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC study was done or is applicable for this type of in vitro diagnostic device. This device is an automated immunoassay for preliminary detection of substances, not an imaging or interpretive diagnostic tool that involves human readers' performance with and without AI assistance.

6. Standalone (Algorithm Only) Performance

The "standalone" performance is essentially what is reported. The Psychemedics HEIA itself is the "algorithm" (the immunoassay system). Its performance is directly compared to the gold standard (LC/MS/MS) without human intervention in the interpretation of the HEIA signal. The entire document focuses on the performance of the device itself.

7. Type of Ground Truth Used

The primary ground truth used is objective chemical analysis via Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS). For precision studies, it involved spiking negative hair with known concentrations of analytes, confirmed by LC/MS/MS validated calibrators and control solutions.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning, as this is an immunoassay device, not an AI/ML algorithm that is 'trained.' The device is a chemical system with reagents. Its method development and optimization would involve various experiments, but these are not referred to as a "training set" in the common AI/ML terminology.

9. How Ground Truth for the Training Set Was Established

Since there isn't a "training set" in the AI/ML sense, this question is not directly applicable. The development and calibration of the immunoassay reagents (anti-methamphetamine monoclonal antibody, methamphetamine labeled recombinant G6PDH, etc.) would involve analytical methods to ensure their specificity and sensitivity. The calibrators and control materials are prepared using drug stocks purchased from commercial vendors with certificates of analysis (Page 10), which serves as the reference for established concentrations.

Ask a specific question about this device

The Lin-Zhi International, Inc. (LZI) Methamphetamine Enzyme Immunoassay for Pictus Analyzers is intended for the qualitative determination of d-methamphetamine in human urine at a cutoff value of 500 ng/mL. The system was calibrated with d-methamphetamine. The assay provides a rapid screening procedure for determining the presence of d-methamphetamine in urine.

The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

Lin-Zhi International, Inc. (LZI) Methamphetamine Enzyme Immunoassay for Pictus Analyzers is intended for the qualitative determination of methamphetamine in human urine, at a cutoff value of 500 ng/mL.

The assay is designed for laboratory use by trained professionals with various automated clinical chemistry analyzers.

This assay provides a rapid screening procedure for assessing the presence of d-methamphetamine in urine. The assay provides only a preliminary analytical result reported as a positive or negative. 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 analyzer photometer reads the absorbance at 340mm at time intervals dictated by the Methamphetamine application stored in the analyzer memory, and the change in absorbance is calculated automatically.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text.

Note: This document describes a traditional in-vitro diagnostic (IVD) device (immunoassay for drug detection) and not an AI/ML-driven medical device, hence many of the requested points related to AI/ML device validation (e.g., number of experts for ground truth, MRMC study, training set details) are not applicable. I will indicate "N/A" for these points.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the study success definitions and the comparison to the predicate device.

• 0-375 ng/mL: 100% Negative
• 500 ng/mL: 49% Negative (41 samples), 51% Positive (43 samples)
• 625-1000 ng/mL: 100% Positive
  Within Run Precision (19-20 samples per level):
• 0-375 ng/mL: 100% Negative
• 500 ng/mL: 60% Negative (12 samples), 40% Positive (8 samples)
• 625-1000 ng/mL: 100% Positive (one sample at 625 showed 19 samples, all positive) |
  | Cross Reactivity: Demonstrate similar cross-reactivity profiles to the predicate device for structurally related compounds. | Pictus P700 vs. Hitachi 717 (Predicate):
• d-Methamphetamine (500 ng/mL): Positive (P700) / 211 (Hitachi)
• d-Amphetamine (50,000 ng/mL): Positive (P700) / 212.1 (Hitachi)
• Methylenedioxyamphetamine (MDA) (72,500 ng/mL): Positive (P700) / 210.1 (Hitachi)
• Methylenedioxymethylamphetamine (MDMA) (1,500 ng/mL): Positive (P700) / 207.8 (Hitachi)
  The results demonstrated "cross-reactivity of the reagents with the Pictus 700 was the same as that demonstrated with the same reagents on the Hitachi 717." |
  | Accuracy - Method Comparison: | Pictus 700 Methamphetamine Tests vs LC/MS Reference (98 samples):
• 0-350 ng/mL (negative samples by LC/MS):
  • LC/MS 30% of CO (Positive): 5 positive
  • LC/MS >50% of COV (Positive): 7 positive
  • LC/MS Very High Positive: 21 positive
  • All samples in this range (5 + 7 + 21 = 33) were reported as positive by Pictus 700 (100.0% agreement for positive samples).
• Between 351 and 649 ng/mL (around cutoff): At least 95% congruent in terms of negative and positive results on either side of the 500 ng/mL cutoff.
  • LC/MS Near CO Negative (351-499 ng/mL): 4 negative, 1 positive (discordant sample 61634620, LC/MS 488, Candidate 514 positive)
  • LC/MS Near CO Positive (501-650 ng/mL): 15 positive, 0 negative
  • The overall accuracy was 98.0% for negative agreement and 100.0% for positive agreement against GC/MS. |
    | On-board Reagent Stability: Reagent must be stable on the analyzer for at least 14 days, with a calibration frequency of 7 days. | The LZI Methamphetamine reagent was found to be "stable on-board the Pictus 700 analyzer for at least 14 days, and calibration frequency is defined at 7 days." The study maintained accuracy over the 14-day period. |

2. Sample sizes used for the test set and the data provenance

• Precision:
  • Total Precision: 84 samples per MAMP level (9 levels tested). Total samples = 84 * 9 = 756 individual sample runs across different levels.
  • Within Run Precision: 19-20 samples per MAMP level (9 levels tested). Total samples = approximately 180 individual sample runs.
• Cross Reactivity: 4 structurally related compounds tested in duplicate.
• Accuracy - Method Comparison: 98 human urine samples.
• On-board Reagent Stability: 3 fresh sample pools, analyzed on Day 1, 3, 6, 7, 10, 13, 14, and 17 in duplicate or triplicate.
• Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be prospective as they involved systematically preparing samples at specific concentrations and testing them, or collecting fresh samples for analysis. This is typical for IVD assay validation studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

N/A. For IVD devices like this, ground truth is established by analytical methods, not human expert consensus. The "ground truth" for the accuracy study was established by Gas or Liquid Chromatography-Mass Spectrometry (GC/MS or LC/MS), which are laboratory-based confirmatory methods.

4. Adjudication method for the test set

N/A. Ground truth was established by LC/MS, an objective analytical method, so no human adjudication was required.

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

N/A. This is not an AI-driven device. It is an automated laboratory assay.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in a sense. The device (Pictus 700 with LZI MAMP reagent) performs the analysis automatically in a "standalone" fashion. The results are then interpreted as positive or negative based on the 500 ng/mL cutoff, which is essentially an "algorithm." There is no human interaction for result generation once samples are loaded. The study directly evaluates this standalone performance against the LC/MS reference method.

7. The type of ground truth used

The ground truth used was analytical measurement by Gas or Liquid Chromatography-Mass Spectrometry (GC/MS or LC/MS). For the purpose of drug testing, these are considered the gold standard confirmatory methods.

8. The sample size for the training set

N/A. This document pertains to an IVD reagent and instrument system, not an AI/ML model that requires a "training set" in the machine learning sense. The device is based on enzyme immunoassay chemistry.

9. How the ground truth for the training set was established

N/A. See point 8. The "training" for such a system involves calibrating the instrument with known calibrators, not training an algorithm on a large dataset.

Ask a specific question about this device

The Rapid TOX Cup II is an in vitro diagnostic drugs of abuse testing device intended for use in the qualitative detection of the following drugs of abuse testing in a human urine specimen: Amphetamines, Barbiturates (Butalbital), Benzodiazepines (Oxazepam), Buprenorphine, Cocaine, MDMA (Methylenedioxymethamphetamine), Methadone, Methamphetamine, Opiates, Oxycodone, Phencyclidine, Marijuana, Tricyclic Antidepressants. The test is intended for over-the-counter use.

Rapid TOX Cup II is a drug test that can detect 1 to 13 drugs in human urine. Rapid TOX Cup II is collection cup with a temperature strip attached. It contains an insert with one or more test strips in the insert. Each test strip can test for up to 4 different drugs. The test is for over-the-counter or professional use. Rapid TOX CUP II is a first step in a 2-step process. The test provides information about the presence of certain drugs in urine. The second step in the process is more specific testing by a laboratory.

Here is a description of the acceptance criteria and the study proving the device meets them, based on the provided text:

This document describes the performance of the Rapid TOX Cup II, a urine drug screening device.

1. Table of Acceptance Criteria and Reported Device Performance

The device is an in vitro diagnostic test designed to qualitatively detect various drugs of abuse in human urine. The acceptance criteria are implicit in the "consumer study" results, which show the device's accuracy at different drug concentrations relative to predefined cutoffs. The "acceptance criteria" are not explicitly stated as numerical targets (e.g., Sensitivity > X%, Specificity > Y%), but rather demonstrated through the concordance of the device's positive and negative results with expected outcomes based on the spiked concentrations.

Below is a summary table demonstrating the device's performance for each tested drug across different concentrations, as reported in the consumer study. The "Rapid TOX Cup II Result" indicates how the device interpreted the prepared samples.

Table 1: Rapid TOX Cup II Reported Device Performance (Consumer Study Results)

Interpretation of Performance:

The results indicate that:

• For samples with "No Drug Present" or "Less than 50% of the cutoff concentration," the device predominantly yielded NEGATIVE results, demonstrating high specificity below the cutoff.
• For samples "Between the cutoff and 50% above the cutoff concentration" and "Greater than 50% above the cutoff concentration," the device consistently yielded POSITIVE results, demonstrating high sensitivity at or above the cutoff.
• For samples "Between 50% below the cutoff and the cutoff concentration," there was a mix of positive and negative results, which is expected for lateral flow assays as performance at these "near cutoff" concentrations can vary. However, the majority of these samples still yielded NEGATIVE results, indicating appropriate cutoff performance.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set: The sample sizes vary per drug type and concentration level. For each drug and cutoff level, there were:
  • Between 80 and 960 samples for "No Drug Present" (Negative).
  • 20 samples for "Less than 50% of the cutoff."
  • 40 samples for "Between 50% below the cutoff and the cutoff."
  • 40 samples for "Between the cutoff and 50% above the cutoff."
  • 20 samples for "Greater than 50% above the cutoff."
  • This totals approximately 140 to 1080 samples per drug/cutoff combination for the consumer study. The document lists 17 unique drug/cutoff combinations, meaning the total number of individual tests performed in the consumer study would be significant.
• Data Provenance: The data was generated through a prospective consumer study. The document does not specify the country of origin for the data or the participants, but given the FDA submission, it is likely that the study was conducted in the United States or in accordance with US regulatory standards.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• Experts and Qualifications: The document does not mention the use of human experts (e.g., radiologists) to establish ground truth for this medical device.
• Ground Truth Establishment: The ground truth for the test set was established by preparing samples with known concentrations of drug analytes. These are "spiked" samples with precise, known quantities of the drugs or their metabolites, relative to the device's specified cutoff levels. This is a common and robust method for establishing ground truth in in vitro diagnostic studies.

4. Adjudication Method for the Test Set

• Adjudication Method: Not applicable. As the ground truth was established by known concentrations in prepared samples, there was no need for adjudication among human readers or experts. The device's output (positive/negative) was compared directly to the known concentration of the spiked sample.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This type of study is typically relevant for interpretative devices (e.g., AI in radiology) where human readers are involved in the interpretation process. The Rapid TOX Cup II is an in vitro diagnostic device that provides a direct "positive" or "negative" qualitative result.
• Effect Size of Human Readers Improvement: Not applicable, as no MRMC study was conducted. The study's purpose was to show the device's performance when interpreted by "untrained consumers" in an OTC setting, comparing their interpretation of the device's visual readout to the true spiked concentrations, rather than comparing human reader performance with and without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Standalone Performance: Not explicitly separated as "algorithm only." The device itself (the Rapid TOX Cup II) is the "algorithm" in this context (a lateral flow immunoassay). The study evaluated how well untrained consumers could generate a result and interpret it from the physical device. Therefore, the reported performance is effectively the "standalone performance" of the device as it would be used by an end-user, including the user's interpretation of the visual output. The device is not an AI algorithm in the traditional sense that operates independently of a user interface or human input for interpretation.

7. Type of Ground Truth Used

• Type of Ground Truth: The ground truth used was known, prepared concentrations of drug analytes in urine samples. This is a form of "laboratory-controlled" or "spiked sample" ground truth, which is highly precise and accurate for evaluating the analytical performance of in vitro diagnostic tests. While clinical outcomes or expert consensus might be used for other types of devices, for a rapid drug screen, known concentrations are the gold standard for analytical validation.

8. Sample Size for the Training Set

• Training Set Sample Size: The document does not mention a "training set" in the context of machine learning or AI algorithm development. The Rapid TOX Cup II is a chemical immunoassay, not an AI or machine learning model. Therefore, the concept of a "training set" and "test set" in the AI sense does not apply to the device's development or validation in this document. The samples described were used for a performance validation study (akin to a test set in the analytical validation context).

9. How the Ground Truth for the Training Set Was Established

• Ground Truth for Training Set: Not applicable, as there is no "training set" for an immunoassay device. The ground truth for the validation study (the "consumer study") was established by precisely preparing urine samples with known concentrations of drug analytes, as detailed in point 7.

Ask a specific question about this device

The Immunalysis Methamphetamine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 500ng/mL and 1000ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Methamphetamine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Methamphetamine. This in-vitro diagnostic device is for prescription use only.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or permitting laboratories to establish quality control procedures.
The Immunalysis Methamphetamine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. GC-MS or Liquid Chromatography / Mass Spectrometry (LC/MS) 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 used.
The Immunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine, Morphine, PCP and Oxazepan. The calibrators are designed for prescription use with immunoassays.

The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal antibodies to Methamphetamine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Methamphetamine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative.
All of the Immunalysis Multi-Drug Calibrators are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.
The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators are prepared by spiking known concentrations of drug analyte into the negative calibrator matrix. These five calibrators (negative, Level 1, 2, 3 and 4) are sold as individual bottles.

Here's an analysis of the provided text regarding the Immunalysis Methamphetamine Urine Enzyme Immunoassay and its performance, structured according to your request:

Device: Immunalysis Methamphetamine Urine Enzyme Immunoassay & Immunalysis Multi-Drug Calibrators
Intended Use: Qualitative and semi-quantitative analysis of Methamphetamine in human urine with automated clinical chemistry analyzers at dual cutoffs of 500ng/mL and 1000ng/mL. For prescription use.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a separate, quantitative target alongside its performance study results. Instead, the studies demonstrate the device's performance, implying that these results meet implicit acceptance criteria for substantial equivalence to the predicate device. For the purpose of this table, I will infer the acceptance criteria from the observed performance and the nature of these types of immunoassays (i.e., that they should accurately classify samples around the cutoff and show no significant interference).

2. Sample Size Used for the Test Set and Data Provenance

• Precision/Cutoff Characterization (Tables 3-6):

  • Test set size: 80 determinations at each of 9 concentration levels per cutoff (0, -75%, -50%, -25%, Cutoff, +25%, +50%, +75%, +100%). This means 80 samples were prepared at each concentration level. The study was performed for 20 days, 2 runs per day in duplicate.
  • Data Provenance: Drug-free urine spiked with methamphetamine. This is prospective data (laboratory prepared). The country of origin is not explicitly stated but implies a US-based laboratory testing context (given the FDA submission).

• Specificity and Cross-Reactivity (Tables 7-10) and Interference (Tables 11-18) including pH and Specific Gravity:

  • Test set size: Not explicitly stated as a count of individual samples for each compound, but results are given for individual compounds at specific concentrations. The implication from the precision study (80 determinations per concentration) might suggest similar rigorous testing for these as well, but it's not confirmed. The overall approach is that each compound was "spiked into drug free urine."
  • Data Provenance: Drug-free urine spiked with relevant compounds. This is prospective (laboratory prepared).

• Method Comparison (Tables 24-33):

  • Test set size: 80 human urine samples (referred to as "clinical urine samples").
  • Data Provenance: "Eighty unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories." This indicates retrospective data from clinical settings. The country of origin for these samples is not explicitly stated but is implied to be within the US given the context of FDA submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

• For the Precision/Cutoff Characterization, Specificity/Cross-Reactivity, and Interference studies, the ground truth was established by laboratory spiking of known concentrations of methamphetamine or other compounds into drug-free urine. No human experts were required to establish this ground truth. The spiked concentrations were "confirmed by mass spectrometry (MS)."
• For the Method Comparison study, the ground truth was established by Mass Spectrometry (LC-MS/MS), which is the "preferred confirmatory method" as stated in the Indications for Use. This is an objective analytical method, not reliant on human expert interpretation.

4. Adjudication Method for the Test Set

Not applicable. The ground truth for the analytical studies was established by spiking known concentrations (laboratory-prepared) and confirmed by Mass Spectrometry (objective analytical method), not by human adjudication of qualitative results.

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

Not applicable. This device is an in-vitro diagnostic immunoassay for detecting substances in urine, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, an MRMC study related to human improvement with AI assistance is not relevant or described.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, this entire study represents a standalone "algorithm only" (device only) performance evaluation. The Immunalysis Methamphetamine Urine Enzyme Immunoassay is an automated clinical chemistry analyzer assay, meaning its output is directly read from the analyzer, without human interpretation of raw data for the primary qualitative or semi-quantitative result. The "human-in-the-loop" would be a lab technician running the sample and interpreting the final pass/fail result based on the analyzer's output relative to the cutoff, but the core performance data presented is the device's direct measurement.

7. The Type of Ground Truth Used

• Precision/Cutoff Characterization, Specificity/Cross-Reactivity, Interference (including pH, specific gravity, Boric Acid): Laboratory-prepared samples with known, spiked concentrations confirmed by Mass Spectrometry (MS).
• Method Comparison: LC-MS/MS confirmation (Liquid Chromatography / Mass Spectrometry), which is considered the "gold standard" or preferred confirmatory method for drug testing.

8. The Sample Size for the Training Set

The document describes performance studies for the Immunalysis Methamphetamine Urine Enzyme Immunoassay. For an immunoassay of this type, the "training set" doesn't typically refer to a data set used to train a machine learning model. Instead, it refers to the reagents and their formulation which are developed and optimized internally by the manufacturer. The document does not provide details on the development (analogous to 'training') data or processes. The reported studies are validation studies demonstrating the final product's performance.

9. How the Ground Truth for the Training Set Was Established

As explained above, for an immunoassay, the concept of a "training set" and establishing its ground truth in the context of machine learning is not directly applicable. The "ground truth" for the calibrators (part of the device, analogous to some aspects of training or reference) is detailed:

• Immunalysis Multi-Drug Calibrators: "Calibrators are manufactured and are tested by mass spectrometry."
• Negative calibrator: "processed, drug free urine matrix... compared to a reference negative standard to ensure that it is free of analyte."
• Non-zero calibrators: "prepared by spiking a known concentration of oxazepam in the negative calibrator matrix."
• "If any of the analytes are not of the acceptable range, then the calibrator is adjusted and re-tested. Values are assigned to the calibrators once the mass spectrometry results are within the acceptable ranges."

This means the ground truth for the calibrators is established through controlled spiking of known concentrations and verification by mass spectrometry.

Ask a specific question about this device

The RapidFRET Oral Fluid Assay for Methamphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for methamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Methamine Calibrators and RapidFRET Oral Fluid Methamphetamine Controls are intended for use only with appropriate RapidFRET Oral Fluid Assay products and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive controls are used to monitor laboratory systems, operators, precision. accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for Methamphetamine is an In Vitro Diagnostic competitive immunoassay used to detect methamphetamine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.

The provided text describes the RapidFRET Oral Fluid Assay for Methamphetamine. Here's an analysis of the acceptance criteria and the study conducted:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal "acceptance criteria" through a defined table or specific performance thresholds for sensitivity, specificity, or accuracy that the device must meet. Instead, the performance characteristics are presented as results from various studies, which imply the expected performance for a successful premarket notification. The de facto acceptance criteria appear to be substantial equivalence to the predicate device (Lin-Zhi International, Inc., LZI Oral Fluid Methamphetamine Enzyme Immunoassay (K131652)) and demonstrating acceptable analytical performance.

However, based on the provided data, we can infer some performance expectations and list the reported outcomes:

• RapidFRET POS / Confirmed POS:
  • ≥150% Cutoff: 39
  • 100-150% Cutoff: 5
  • 50-100% Cutoff: 2‡ (These would ideally be negative by the screening cutoff)

Ask a specific question about this device

Healgen MDMA (Ecstasy) Test is an immunochromatographic assay for the qualitative determination of Methylenedioxymethamphetamine in human urine at a Cut-Off concentration of 500 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result: GC/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 result is positive. For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.

Healgen Phencyclidine Test is an immunochromatographic assay for the qualitative determination of Phencyclidine in human urine at a Cut-Off concentration of 25 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/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 result is positive. For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.

Healgen MDMA (Ecstasy) Test and Healgen Phencyclidine Test are immunochromatographic assays for Methylenedioxymethamphetamine and Phencyclidine. Each assay test is a lateral flow system for the qualitative detection of Methylenedioxymethamphetamine and Phencyclidine (target analyte) in human urine. The products are in vitro diagnostic devices, which come in the form of: Strips, Cassettes, DipCards, or Cups. Each product contains a Test Device (in one of the four formats), and a package Each test device is sealed with a desiccant in an aluminum pouch. insert.

Here's a breakdown of the acceptance criteria and study information for the Healgen MDMA (Ecstasy) Test and Healgen Phencyclidine Test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated in a single section as pass/fail thresholds. Instead, the performance characteristics studies demonstrate the device's accuracy and reliability against the established cut-off values as compared to GC/MS, which serves as the gold standard.

Healgen MDMA (Ecstasy) Test Performance Summary (Across all formats: Strip, Cassette, Cup, Dip Card)

• Samples +25% Cut-off: Positive result
• Samples at Cut-off: Expected mix of positive/negative | MDMA (Ecstasy):
• Samples at -100%, -75%, -50%, -25% Cut-off: 50-/0+ (All negative)
• Samples at +25%, +50%, +75%, +100% Cut-off: 50+/0- (All positive)
• Samples at Cut-off: Varied (e.g., Strip, Cassette: 22-/28+; Dip Card: 24-/26+; Cup: 30-/20+) - Indicates appropriate sensitivity around the cut-off. |
  | Cut-off Verification:
• All samples at and above +25% cut-off: Positive
• All samples at and below -25% cut-off: Negative | MDMA (Ecstasy): Verified (all positive at/above +25% cut-off, all negative at/below -25% cut-off).
  Phencyclidine: Verified (all positive at/above +25% cut-off, all negative at/below -25% cut-off). |
  | Interference: No clinically significant interference from common substances at 100 µg/mL. | No differences observed for different formats. Numerous compounds listed showed no interference at 100 µg/mL. |
  | Specificity: Cross-reactivity analysis as expected. | MDMA (Ecstasy): 3,4-Methylenedioxyamphetamine HCl (MDA) 17% cross-reactivity, 3,4-Methylenedioxyethylamphetamine (MDEA) 167% cross-reactivity. d-methamphetamine 20% cross-reactivity. d-, l-amphetamine, l-methamphetamine not detected at >100,000 ng/mL.
  Phencyclidine: 4-Hydroxy Phencyclidine 28% cross-reactivity. |
  | Effect of Urine Specific Gravity and pH: Accurate results across a range of specific gravities (1.000-1.035) and pH (4-9). | Results all positive for samples at and above +25% cut-off and all negative for samples at and below -25% Cut-Off. No differences observed for different formats. |
  | Method Comparison (Professional User): High agreement with GC/MS. | Each format across MDMA and Phencyclidine tests showed high agreement with GC/MS, with discordant results primarily near the cut-off concentrations (as expected for qualitative tests). Example for MDMA Strip, Viewer A: 13/16 (81.25%) agreement at Near Cutoff Positive, 24/24 (100%) at High Positive. 10/10 (100%) at Negative, 15/15 (100%) at Low Negative. |
  | Lay-User Performance: High percentage of correct results, easy-to-follow instructions. | MDMA (Ecstasy):
• Samples at -100%, -75%, -50% Cut-off: 100% correct negative.
• Samples at -25% Cut-off: 95% correct negative.
• Samples at +50%, +75% Cut-off: 100% correct positive.
• Samples at +25% Cut-off: 95% correct positive.
  Similar results for Phencyclidine with some formats showing 90% at -25% and +25% Cut-off.
  All lay users indicated device instructions can be easily followed (Flesch-Kincaid Grade Level 7). |

Healgen Phencyclidine Test Performance Summary (Across all formats: Strip, Cassette, Cup, Dip Card)

• Samples +25% Cut-off: Positive result
• Samples at Cut-off: Expected mix of positive/negative | Phencyclidine:
• Samples at -100%, -75%, -50%, -25% Cut-off: 50-/0+ (All negative)
• Samples at +25%, +50%, +75%, +100% Cut-off: 50+/0- (All positive)
• Samples at Cut-off: Varied (e.g., Strip: 20-/30+; Cassette: 18-/32+; Dip Card: 22-/28+; Cup: 16-/34+) - Indicates appropriate sensitivity around the cut-off. |
  | Cut-off Verification:
• All samples at and above +25% cut-off: Positive
• All samples at and below -25% cut-off: Negative | MDMA (Ecstasy): Verified (all positive at/above +25% cut-off, all negative at/below -25% cut-off).
  Phencyclidine: Verified (all positive at/above +25% cut-off, all negative at/below -25% cut-off). |
  | Interference: No clinically significant interference from common substances at 100 µg/mL. | No differences observed for different formats. Numerous compounds listed showed no interference at 100 µg/mL. |
  | Specificity: Cross-reactivity analysis as expected. | MDMA (Ecstasy): 3,4-Methylenedioxyamphetamine HCl (MDA) 17% cross-reactivity, 3,4-Methylenedioxyethylamphetamine (MDEA) 167% cross-reactivity. d-methamphetamine 20% cross-reactivity. d-, l-amphetamine, l-methamphetamine not detected at >100,000 ng/mL.
  Phencyclidine: 4-Hydroxy Phencyclidine 28% cross-reactivity. |
  | Effect of Urine Specific Gravity and pH: Accurate results across a range of specific gravities (1.000-1.035) and pH (4-9). | Results all positive for samples at and above +25% cut-off and all negative for samples at and below -25% Cut-Off. No differences observed for different formats. |
  | Method Comparison (Professional User): High agreement with GC/MS. | Each format across MDMA and Phencyclidine tests showed high agreement with GC/MS, with discordant results primarily near the cut-off concentrations (as expected for qualitative tests). Example for Phencyclidine Strip, Viewer A: 13/16 (81.25%) agreement at Near Cutoff Positive, 24/24 (100%) at High Positive. 10/10 (100%) at Negative, 15/15 (100%) at Low Negative. |
  | Lay-User Performance: High percentage of correct results, easy-to-follow instructions. | MDMA (Ecstasy):
• Samples at -100%, -75%, -50% Cut-off: 100% correct negative.
• Samples at -25% Cut-off: 95% correct negative.
• Samples at +50%, +75% Cut-off: 100% correct positive.
• Samples at +25% Cut-off: 95% correct positive.
  Similar results for Phencyclidine with some formats showing 90% at -25% and +25% Cut-off.
  All lay users indicated device instructions can be easily followed (Flesch-Kincaid Grade Level 7). |

2. Sample size used for the test set and the data provenance

• Precision Study:

  • Test set size: For each drug (MDMA/Phencyclidine) and each device format, 9 different concentration levels were tested. For each concentration level, 50 tests were performed (2 runs/day for 25 days). So, 9 concentrations * 50 tests/concentration = 450 tests per lot. Since there are 3 lots mentioned per format, this would be 3 lots * 450 tests/lot = 1350 tests per format for each drug.
  • Data Provenance: Samples were prepared by spiking drug in negative urine samples, suggesting these are prospectively prepared, controlled samples. The text does not specify the country of origin, but the submission is to the FDA, implying studies likely conducted in or for the US market. The samples were confirmed by GC/MS.

• Cut-off Verification Study:

  • Test set size: 150 samples were tested for each drug, equally distributed at 5 concentrations (-50% cut-off, -25% cut-off, cut-off, +25% cut-off, +50% cut-off).
  • Data Provenance: Samples were prepared by spiking drug in negative samples, indicating prospectively prepared, controlled samples.

• Interference Study:

  • Test set size: Not explicitly stated as a number of samples, but numerous potential interfering substances were added to drug-free urine and urine containing target drugs at 25% above cut-off levels. Each type of sample/interferent was tested using three batches of each device for all formats.
  • Data Provenance: Prepared samples, suggesting prospectively prepared, controlled samples.

• Specificity Study:

  • Test set size: Not explicitly stated as a number of samples, but drug metabolites and other components were tested using three batches of each device for all formats.
  • Data Provenance: Prepared samples, suggesting prospectively prepared, controlled samples.

• Effect of Urine Specific Gravity and pH Study:

  • Test set size: Urine samples across a range of specific gravities (1.000-1.035) and pH (4-9) were spiked with target drugs at 25% below and 25% above cut-off levels. These were tested using three batches of each device for all formats.
  • Data Provenance: Prepared samples, suggesting prospectively prepared, controlled samples.

• Comparison Studies (Professional Users):

  • Test set size: For each drug (MDMA and Phencyclidine) and each format (Strip, Cassette, Cup, Dip Card), 80 unaltered clinical samples were used (40 negative and 40 positive). So, for MDMA, 4 formats * 80 samples/format = 320 samples. For Phencyclidine, 4 formats * 80 samples/format = 320 samples.
  • Data Provenance: Unaltered clinical samples, which were blind labeled. The text does not specify the country of origin, but it is retrospective in nature given they are "unaltered clinical samples." (The samples were analyzed by GC/MS, meaning the true drug concentration was known retrospectively).

• Lay-User Study:

  • Test set size: 557 lay persons tested MDMA devices and 555 lay persons tested Phencyclidine devices. Total of 1112 individuals. For each drug, samples were prepared at 7 concentration levels (negative, +/-75%, +/-50%, +/-25% of cutoff). For each concentration, 19-20 samples were tested. Thus, for MDMA: (3 * 20 samples) + (1 * 19 samples for -50% cutoff) + (1 * 20 samples for -25% cutoff) + (1 * 20 samples for +25% cutoff) + (1 * 20 samples for +50% cutoff) + (1 * 19 samples for +75% cutoff) = ~139 unique samples tested across different concentrations for each format (though the table headers suggest 20 samples per concentration usually). The 557 and 555 refers to the number of users, implying each user got at least one sample.
  • Data Provenance: Samples were prepared by spiking drugs into drug-free pooled urine specimens, making this a prospectively prepared, controlled sample study. The concentrations were confirmed by GC/MS. The study was performed at "three intended user sites," but country of origin is not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Professional User Comparison Study:

  • Ground Truth: Established by GC/MS (Gas Chromatography/Mass Spectrometry) results. GC/MS is a highly accurate analytical method, considered the gold standard for drug confirmation.
  • Experts for Ground Truth: Not applicable in the traditional sense of human readers. The ground truth is established by a diagnostic laboratory method (GC/MS).
  • Human Readers of the Device: Three "laboratory assistants" were used for each format. Their specific qualifications are not detailed beyond "laboratory assistants."

• Precision, Cut-off, Interference, Specificity, Effect of Urine Specific Gravity and pH Studies:

  • Ground Truth: Established primarily by GC/MS for confirmation of spiked drug concentrations.
  • Experts for Ground Truth: Not applicable in the traditional sense.

• Lay-User Study:

  • Ground Truth: Established by GC/MS confirmation of the spiked urine sample concentrations.
  • Experts for Ground Truth: Not applicable.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

• Precision, Cut-off, Interference, Specificity, Effect of Urine Specific Gravity and pH Studies:

  • No adjudication method is described for interpreting the results of the device itself (e.g., if there were conflicting results). However, for the precision study, three different operators performed the tests, suggesting individual readings were recorded. The summary tables aggregate these results. The ground truth (spiked concentration) was confirmed by GC/MS prior to testing.

• Comparison Studies (Professional Users):

  • For the discordant results in the comparison studies (Table: Discordant Results of MDMA (Ecstasy) Strip, etc.), it shows individual "Viewer" results (Viewer A, B, C) compared to the GC/MS result. This implies no adjudication method was applied to the device readings to establish a single device result. Instead, the individual results of the three viewers were compared directly to the GC/MS ground truth. They are presenting individual agreement/disagreement.

• Lay-User Study:

  • Each lay person individually performed the test and interpreted the results. There was no adjudication method among lay users. Each lay user's result was compared to the GC/MS ground truth.

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 involving AI assistance was NOT done.
  • This device is an in vitro diagnostic (IVD) test (immunochromatographic assay for drug detection in urine), not an AI-powered image analysis or diagnostic support system for human readers.
  • The "Viewers" mentioned in the comparison studies are human laboratory assistants interpreting the visual lines on the test strips/cassettes, not radiologists or clinicians integrating AI outputs. Their performance alone, both individually and in aggregate, is being evaluated against the GC/MS gold standard.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

• Yes, in essence, the "device" itself is a standalone test.
  • For an IVD like this, the "algorithm" is the biochemical reaction and visual detection mechanism. The testing (precision, cut-off, interference, specificity, specific gravity/pH) directly evaluates the device's performance in detecting the target analytes in urine samples. The "professional user" comparison and "lay user" study involve human interpretation, but the core performance characteristics are intrinsic to the device's design. There isn't a separate "algorithm" being evaluated beyond the physical test kit itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

• The primary ground truth used for all performance studies (Precision, Cut-off, Interference, Specificity, Specific Gravity/pH Effect, Professional User Comparison, Lay-User Study) was Gas Chromatography/Mass Spectrometry (GC/MS).
  • GC/MS is a highly reliable and recognized analytical method for confirming the presence and concentration of drugs in biological samples and is considered the gold standard for such applications.

8. The sample size for the training set

• There is no stated training set for this device as it is an immunochromatographic assay, not a machine learning or AI algorithm in the context of typical software device development. The device's performance is based on its biochemical design and manufacturing, not a learned model from a dataset.

9. How the ground truth for the training set was established

• Not applicable, as there is no training set for this type of IVD device.

Ask a specific question about this device

First Sign™ Drug of Abuse Tests are immunochromatographic assays for the qualitative determination of Oxazepam , Methamphetamine, and Morphine in human urine at cut-off concentrations of 300 ng/mL, and 2000 ng/mL, respectively. The tests are available in a Cup format and a Dip Card format.

The tests may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The tests provide only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

First Sign™ Drug of Abuse Tests are immunochromatographic assays. Each assay test is a lateral flow system for the qualitative detection of Oxazepam , Methamphetamine , and Morphine in human urine. The products are single-use in vitro diagnostic devices, which come in the formats of DipCards or Cups. Each test kit contains a Test Device (in one of the two formats), a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

Here's an analysis of the acceptance criteria and study detailed in the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in terms of specific quantitative benchmarks (e.g., "sensitivity must be >90%"). Instead, it describes performance characteristics and then presents the results of studies to demonstrate that the device performs acceptably. The implied acceptance criterion for these qualitative drug tests is that they generally agree with GC/MS results, especially at and significantly above/below cut-off values.

Based on the provided performance characteristics, here's a summary:

2. Sample Size and Data Provenance (Test Set)

• Sample Size (Trained Professionals, Method Comparison):
  • For each of the three drugs (Oxazepam, Methamphetamine, Morphine) and each format (Dip Card, Cup), 80 clinical samples were used.
  • Total samples for method comparison: 3 drugs * 2 formats * 80 samples/drug/format = 480 samples.
  • Breakdown of 80 samples: 10 Negative, 10 Low Negative, 20 Near Cutoff Negative, 15 Near Cutoff Positive, 25 High Positive.
• Sample Size (Lay User Study):
  • 280 lay persons for Oxazepam devices.
  • 280 lay persons for Methamphetamine devices.
  • 280 lay persons for Morphine devices.
  • Each lay person tested 1 blind labeled sample and a device.
  • Total samples tested by lay users: Roughly 280 samples/drug * 3 drugs = 840 samples.
• Data Provenance (Method Comparison): "unaltered clinical samples" - implies retrospective collection, origin unknown based on the text.
• Data Provenance (Lay User Study): "Urine samples were prepared... by spiking drugs into drug free-pooled urine specimens." This indicates the samples were synthesized or spiked rather than naturally occurring clinical samples, and then blind-labeled.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

• Number of Experts:
  • Method Comparison (Professional User): "three different laboratory assistants for each format of the device." Total of 6 unique readers (3 for dip card, 3 for cup) if they were distinct, or 3 if the same 3 read both formats (the wording "Different set of operators tested each format" in the precision study suggests distinct operators, but here it states "for each format", which could mean the same set of 3 rotated). The data is presented as Viewer A, B, C for each.
  • Lay User Study: 280 lay persons per drug. Not "experts" in the traditional sense, but the intended users.
• Qualifications of Experts: The "three different laboratory assistants" are not further qualified (e.g., radiologist with 10 years of experience).

4. Adjudication Method (Test Set)

• None specified for the professional user readings. The raw results from each "Viewer" (laboratory assistant) are presented individually, and then compared against the GC/MS result. They are not pooled or adjudicated to form a single "device" result.
• For the Lay User Study: There is no "adjudication" between lay users. Each lay user's individual result is recorded and compared to the GC/MS confirmed concentration.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC comparative effectiveness study was done to measure human reader improvement with AI vs. without AI assistance. This device is a standalone qualitative diagnostic test (immunochromatographic assay), not an AI-assisted interpretation tool for human readers.

6. Standalone Performance (Algorithm Only)

• Yes, a standalone performance was done, but it's not an "algorithm" in the typical AI sense. The device itself (the immunochromatographic assay) is designed to provide a result (positive/negative) based on a chemical reaction, which can then be visually interpreted. The precision studies, cut-off studies, interference, specificity, and specific gravity/pH studies all demonstrate the standalone performance of the device without explicit human interpretation variability considered (though a human reads the test line).
• The "Method Comparison" and "Lay-user study" then introduce the human element (laboratory assistants and lay users, respectively) reading these standalone device results.

7. Type of Ground Truth Used (Test Set)

• Gas Chromatography/Mass Spectrometry (GC/MS) was explicitly used as the preferred confirmatory method for establishing ground truth for both the professional method comparison study and for confirming the concentrations of the spiked samples in the lay user study and precision/cut-off studies.

8. Sample Size for the Training Set

• The document describes performance characteristics and equivalence to a predicate device, but does not specify a separate "training set" for the development of the device itself or for any AI/algorithmic component (as there isn't one). The studies described are performance validation studies.

9. How the Ground Truth for the Training Set was Established

• Not applicable as no "training set" is mentioned in the context of device development. The ground truth for all performance evaluation studies (precision, cut-off, method comparison, lay user) was established using GC/MS.

Ask a specific question about this device

The RapidFRET Oral Fluid Assay for MDMA is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Methylenedioxymethamphetamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid MDMA Calibrator Set and RapidFRET Oral Fluid MDMA Control Set are intended for use only with the RapidFRET Oral Fluid Assay for MDMA and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for MDMA is an In Vitro Diagnostic competitive immunoassay used to detect MDMA in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive result. Controls are used to establish and monitor precision and accuracy.

Here's an analysis of the provided text to extract the requested information about the RapidFRET Oral Fluid Assay for MDMA:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the expected results and agreement percentages reported.

*Note: The 97% for MS NEG agreement is calculated from the provided table: 200 RapidFRET NEG when MS NEG, and 6+ RapidFRET POS when MS NEG (false positives). So, 200 / (200 + 6) = 200/206 ≈ 97%.

2. Sample Sizes and Data Provenance

• Precision and Analytical Sensitivity Test Set:
  • Sample Size: 279 at 0%, 279 at 25%, 278 at 50%, 279 at 75%, 279 at 100%, 278 at 125%, 263 at 150%, 294 at 175%, 278 at 200% of cutoff. These were spiked oral fluid pools.
  • Data Provenance: Not explicitly stated, but likely laboratory-prepared samples. It doesn't specify country of origin or if it's retrospective/prospective.
• Correlation with MS Quantitation Test Set:
  • Sample Size: 325 neat oral fluid samples.
  • Data Provenance: Collected from "volunteers potentially positive and negative for MDMA." This suggests prospective collection for the purpose of the study. Country of origin not specified, but the applicant's address is in California, USA, making it probable the study was conducted there.
• Cross Reactivity and Analytical Specificity Test Set:
  • Sample Size:
    • Structurally related compounds: A library of over 170 compounds. Specific numbers of samples per compound are not given, but they were spiked into neat oral fluid aliquots (likely 0, 25, 75 ng/mL MDMA).
    • Common substances: Not specified per substance, but implied to be multiple (volunteers for some, spiked aliquots for others).
  • Data Provenance: Laboratory-prepared samples (spiked) and samples from volunteers.

3. Number of Experts and Qualifications for Ground Truth

• Precision and Analytical Sensitivity: No human experts were explicitly mentioned for ground truth. The ground truth was established by the known concentrations of MDMA spiked into the oral fluid pools.
• Correlation with MS Quantitation: The ground truth was established by GC/MS or LC/MS/MS results. No human experts are mentioned for interpreting these confirmatory tests, as they are analytical methods providing quantitative results.
• Cross Reactivity and Analytical Specificity: No human experts were explicitly mentioned. The ground truth was based on the known concentrations of MDMA and cross-reactants spiked into the samples, or the known consumption of common substances.

4. Adjudication Method for the Test Set

• Precision and Analytical Sensitivity: Not applicable, as samples were spiked at known concentrations.
• Correlation with MS Quantitation: Not applicable. GC/MS or LC/MS/MS provides a definitive analytical result, not a judgment requiring adjudication.
• Cross Reactivity and Analytical Specificity: Not applicable. Ground truth was based on known concentrations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, not a medical imaging or interpretive device that typically involves human readers in this context. It performs a qualitative screen (positive/negative) based on a cut-off.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop)

• Yes, the studies presented are all standalone performance studies. The RapidFRET Oral Fluid Assay for MDMA is an automated laboratory assay that performs a qualitative screen without human interpretation involved in the direct result generation. The performance metrics (precision, analytical sensitivity, correlation with MS) directly reflect the algorithm's performance.

7. Type of Ground Truth Used

• Precision and Analytical Sensitivity: Known concentrations of spiked MDMA (analytical truth).
• Correlation with MS Quantitation: Confirmed analytical results by GC/MS or LC/MS/MS (gold standard analytical truth).
• Cross Reactivity and Analytical Specificity: Known concentrations of spiked compounds (analytical truth) and known consumption of common substances (experiential/known truth).

8. Sample Size for the Training Set

• The document does not specify a separate training set or its sample size. This type of immunoassay device is typically developed through chemical and biological experimentation to establish reagent formulations and cutoff values, rather than through machine learning training on a large dataset in the way a modern AI algorithm would be. The experiments described appear to be validation/verification studies.

9. How Ground Truth for the Training Set Was Established

• As no training set is explicitly mentioned, the establishment of ground truth for it is not described. The device's operational parameters (e.g., cutoff) would be derived from laboratory experiments during development.

Ask a specific question about this device

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of d-methamphetamine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value 50 ng/mL. 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 LZI Oral Fluid Methamphetamine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value 50 ng/mL.

The LZI Oral Fluid Methamphetamine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.

The assay provides only a preliminary analytical result. A more specific alternative chemical method 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 Methamphetamine assay is a homogeneous enzyme immunoassay with ready-to-use 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, methamphetamine-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 methamphetamine-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 Methamphetamine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

The R1 solution contains mouse monoclonal anti-methamphetamine antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09%) as a preservative. The R2 solution contains glucose-o-phosphate dehydrogenase (G6PDH) labeled with methamphetamine in buffer with sodium azide (0.09%) as preservative.

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay calibrators and controls designated for use at the 50 ng/mL cutoffs contain 0, 20, 37.5, 50, 62.5, 100, and 140 ng/mL of dmethamphetamine in human oral fluid with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.

The LZI Oral Fluid Collector is a 50 mL polypropylene collection tube. It is a non-sterile centrifuge tube with a screw-on cap and printed graduations (United Lab Plastics, Catalog#UP2262).

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state numerical acceptance criteria for qualitative agreement, but "100.0% agreement with positive" and "95.2% agreement with negative" are presented as favorable performance. The precision data indicates 100% concordance with expected results at various concentrations relative to the cutoff.

2. Sample Size Used for the Test Set and Data Provenance

• Test Set Sample Size: "a total of eighty-five (85) clinical unaltered samples" were used for method comparison.
• Data Provenance: The text does not specify the country of origin. It indicates the samples were "clinical unaltered samples," implying they were collected from human subjects in a clinical setting, making them prospective or retrospective clinical samples. The exact nature (prospective vs. retrospective) is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of immunoassay device relies on a "confirmatory method" for establishing ground truth, not typically human expert consensus for individual results.

• Number of Experts: Not applicable in the traditional sense of human consensus.
• Qualifications of Experts: Not applicable. The ground truth is established by analytical methods.

4. Adjudication Method for the Test Set

Not applicable for this type of device where the ground truth is established by a specific analytical method. The device's results are compared directly to the results from the confirmatory method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for image-based diagnostic devices where human readers interpret images. This device is an in-vitro diagnostic assay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies reported are standalone performance studies of the device (immunoassay) itself. The "Immunoassay Result" tables directly show the device's output (Positive/Negative) for given sample concentrations. The method comparison directly evaluates the device against a gold standard analytical method without human interpretation of the device's output other than reading the final result.

7. The Type of Ground Truth Used

The type of ground truth used is an alternative chemical method, specifically Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS). These are considered the "preferred confirmatory method[s]" for drug detection in oral fluid.

8. The Sample Size for the Training Set

The document does not report a specific sample size for a training set. Immunoassays like this are developed through a different process involving reagent formulation and optimization rather than machine learning training on a large dataset in the way a software algorithm would be. The "within run" and "total precision" studies use 22 and 88 determinations per concentration, respectively, but these are for performance evaluation, not a "training set."

9. How the Ground Truth for the Training Set Was Established

Since a "training set" in the context of machine learning is not explicitly mentioned or relevant for this type of device, the method for establishing ground truth for such a set is not described. The device's performance is demonstrated by comparing its results to established analytical methods for clinical samples and spiked samples with known concentrations.

Ask a specific question about this device