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The Alinity o Benzodiazepines Reagent Kit is a homogeneous enzyme immunoassay intended for the qualitative and/or semiquantitative determination of the presence of benzodiazepines and their metabolites in human urine at a cutoff concentration of 200 ng/mL (0.700 umol/L) on the Alinity c analyzer.

The assay is intended to be used in laboratories and provides a rapid analytical screening procedure to detect benzodiazepines in human urine. This assay is calibrated against oxazepam. This product is intended to be used by trained professionals only.

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

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used 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 and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

The Alinity c Benzodiazepines Reagent Kit is a homogeneous enzyme immunoassay with liquid ready to-use reagents. The assay uses a specific antibody that can detect most benzodiazepines and their metabolites in urine. The assay is based on competition between a drug labeled with glucose-6- phosphate dehydrogenase (G6PDH), and free sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the druq labeled with G6PDH and causes a decrease in enzyme activity. In the presence of free drug occupies the antibody binding sites, allowing the drug bound G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct relationship between the drug concentration in urine and enzyme activity is determined spectrophotometrically at 340 nm by measuring the conversion of nicotinamide adenine dinucleotide (NAD) to NADH.

Benzodiazepines are sedative-hypnotic drugs, which are subject to abuse. Benzodiazepines are include a wide variety of drugs such as alprazolam, diazepam, lorazepam, oxazepam, and triazolam. They are absorbed and metabolized at different rates, resulting in various psychoactive effects. Baselt describes the metabolism and toxicology of numerous benzodiazepines, including alprazeoam, chlordiazepoxide, clobazam, clorazepate, diazepan, estazolam, flunitrazepam, halazepam, medazepam, midazolam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, and triazolam.

The Alinity c Benzodiazepines Reagent Kit is a first-line device, which may be used by medical personnel, along with clinical observations, as an aid for indicating Benzodiazeoine abuse through detection of benzodiazepines or their metabolites in urine

The document provided is a 510(k) Premarket Notification for an in vitro diagnostic device, the Alinity c Benzodiazepines Reagent Kit. It focuses on demonstrating substantial equivalence to a predicate device, rather than proving the device meets a specific set of acceptance criteria for an AI model.

Therefore, many of the requested details regarding AI model acceptance criteria, ground truth establishment, expert adjudication, MRMC studies, and training/test set sample sizes for an AI study are not present in this document. This document describes the performance characteristics of a laboratory immunoassay, which is a chemical assay, not an AI or software algorithm that interprets images or complex data.

However, based on the provided text, I can extract the following information relevant to the device's analytical performance and its comparison to a predicate, which serves as a form of "acceptance criteria" for a diagnostic kit:

1. A table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" in a typical table format for an AI model's performance metrics (e.g., sensitivity, specificity, AUC with predefined thresholds). Instead, it describes the performance observed and compares it to a predicate device, often noting if they are "identical" or "substantially equivalent." The performance data presented are for specific analytical studies of the reagent kit.

Here's an attempt to structure the performance characteristics as reported, which act as the evidence for "acceptance" (i.e., substantial equivalence):

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

• Test Set Sample Size:

  • Accuracy and Method Comparison: The document states that the Alinity c Benzodiazepines Reagent Kit demonstrated "equivalent performance" when compared to LC-MS/MS, yielding "positive agreement was 100.00%, negative agreement was 96.96%, and overall agreement was 98.41%". While percentages are given, the absolute number of samples used for this accuracy study is not explicitly stated in the provided text.
  • Accuracy by Recovery and Dilution Linearity: A "series of samples" were analyzed, but the specific number is not stated.
  • Precision (Within-Laboratory and Reproducibility): The percentages of correctly read samples are given, but the underlying number of samples/tests performed is not explicitly stated.
  • On-Board Reagent Stability: "one lot" was used, but the number of tests or samples is not explicitly stated.

• Data Provenance (country of origin, retrospective/prospective): Not specified in the provided text.

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

This is not applicable as this is an in vitro diagnostic (IVD) chemical assay, not an AI product requiring expert review of medical images or data for ground truth. The ground truth for chemical assays is typically established by a reference method.

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

Not applicable, as this is an IVD chemical assay, not an AI product. Ground truth is established by a reference method.

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, as this is an IVD chemical assay, not an AI product involving human readers.

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

The device (Alinity c Benzodiazepines Reagent Kit) is a standalone diagnostic test (specifically, an enzyme immunoassay) that provides results without human interpretation of raw assay data. The results (qualitative or semiquantitative determination of benzodiazepine presence) are generated by the Alinity c analyzer using the reagent kit. This is inherently a "standalone" analytical performance.

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

For the Accuracy and Method Comparison study, the reference method (ground truth) used was Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). This is explicitly stated: "The Alinity c Benzodiazepines Reagent Kit demonstrated equivalent performance on the Alinity c analyzer when compared to the reference LC-MS/MS". The document also mentions GC/MS or LC-MS/MS as the "preferred confirmatory method" in the Indications for Use.

8. The sample size for the training set:

Not applicable. This is an IVD chemical assay; there is no "training set" in the context of machine learning model development. The assays are developed and validated using a different process than AI models.

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

Not applicable, as there is no training set for an AI model. For the chemical assay, "ground truth" for development and validation would involve well-characterized samples and reference methods like LC-MS/MS. The calibrators and controls for the assay are stated to contain Oxazepam and are traceable to a commercial source with 98% purity.

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The DRI™ Ecstasy Plus Assay is a homogeneous enzyme immunoassay intended for the qualitative or semiquantitative determination of ecstasy drugs in human urine. The assay provides a simple and rapid analytical screening procedure for detecting ecstasy drugs at a cutoff level of 500 ng/mL. The product is intended for use in clinical laboratories only.

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/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.

DRI Ecstasy Plus Assay is a homogeneous enzyme immunoassay intended for the qualitative or semiquantitative determination of ecstasy drugs in human urine. The assay provides a simple and rapid analytical screening procedure for detecting ecstasy drugs at a cutoff level of 500 ng/mL.

DRI Ecstasy Plus Assay is a class assay. Ecstasy drugs represent a group of ring substituted methylenedioxy analogues of amphetamine including 3, 4 methylenedioxyamphetamine (MDA), 3, 4 - methylenedioxymethamphetamine (MDMA) and 3, 4 - methylenedioxyethylamphetamine (MDEA). They are central nervous system (CNS) stimulants popularly abused for their psychotropic effects and are listed by the U.S. Drug Enforcement Administration as Schedule | (no accepted medical application with great abuse potential).

The provided document is a 510(k) Pre-market Notification from the FDA regarding the DRI™ Ecstasy Plus Assay. This is a medical device for in-vitro diagnostics, specifically a homogeneous enzyme immunoassay for detecting ecstasy drugs in human urine. The document mainly focuses on demonstrating substantial equivalence to a predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document describes the performance characteristics and states the acceptance criteria (stated as "met the acceptance criteria" or specific percentage/range values).

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

The document does not explicitly state the sample size used for the test set. It mentions "Negative sample agreement" and "Positive sample agreement" in the method comparison and "structurally unrelated compounds were spiked into negative pool urine at the tested concentrations" for specificity, but no specific numbers of samples are provided.

The data provenance is also not stated. It does not specify the country of origin of the data or whether the studies were retrospective or prospective.

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

For this type of in-vitro diagnostic device (immunoassay for drug detection), the ground truth is typically established by alternative chemical methods (e.g., GC/MS or LC-MS/MS), not by expert human readers. Therefore, the concept of "experts used to establish the ground truth" in the traditional sense of clinical image review is not applicable here. The document states: "A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method."

4. Adjudication Method for the Test Set

Since the ground truth is established by alternative chemical methods like GC/MS or LC-MS/MS, an adjudication method for reconciling expert opinions is not applicable. The result from the confirmatory chemical method serves as the definitive 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. This device is an in-vitro diagnostic immunoassay, not an AI-powered diagnostic tool requiring human interpretation or a multi-reader multi-case study. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not relevant to this submission.

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

Yes, in a sense. The "performance testing" described (Precision, Method Comparison, Specificity, Interference, Stability) represents the standalone performance of the assay itself. The immunoassay provides a direct analytical result (qualitative or semi-quantitative) without human interpretation affecting the primary outcome of detection. The device's output is an objective measurement (e.g., optical density change leading to a positive/negative determination), rather than an image requiring human interpretation.

7. The Type of Ground Truth Used

The type of ground truth used is confirmatory analytical methods, specifically Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS). This is explicitly stated as the "preferred confirmatory method" to obtain a "confirmed analytical result."

8. The Sample Size for the Training Set

The document does not mention a training set or its sample size. Immunoassays are typically developed and validated using a series of laboratory experiments with known samples (spiked urine, controls, clinical samples confirmed by reference methods) rather than being "trained" on a dataset in the way an AI algorithm is. The development process would involve optimizing reagents and assay conditions but doesn't usually involve a "training set" in the machine learning context.

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

As there is no mention of a "training set" in the context of an immunoassay, the establishment of its ground truth is not applicable as outlined for AI/ML devices. The "ground truth" for developing and validating such an assay would be established by preparing samples with known concentrations of the target analytes and confirming those concentrations using gold-standard analytical techniques like GC/MS or LC-MS/MS.

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The Alinity c Tricyclic Antidepressants Reagent Kit is a homogeneous enzyme immunoassay intended for use in the qualitative and/or semiquantitative determination of the presence of tricyclic antidepressants (TCAs) in human serum or plasma at a cutoff concentration of 300 ng/mL on the Alinity c system in patients suspected of drug overdose.

The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by confirmatory method such as Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS), or for permitting laboratories to establish control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

For In Vitro Diagnostic Use Only.

The Alinity c Tricyclic Antidepressants Reagent Kit is an automated clinical chemistry assay and a homoqeneous enzyme immunoassay using ready-to-use liquid reagents. The assay uses polyclonal antibodies that detect most tricyclic antidepressants in serum or plasma. The assay is based on the competition between an enzyme-labeled drug and the drug from the serum or plasma for a fixed number of specific antibody binding sites. In the absence of drug from the sample, the specific antibody binds to the drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the serum or plasma and the enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340/416 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

The Alinity c Tricyclic Antidepressants Reagent Kit is supplied as a two liquid reagent kit (R1 and R2). They are included within the same kit, see details below:

• Antibody/Substrate Reagent (R1): Contains polyclonal anti-tricyclics antibodies ● (sheep), glucose-6- phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as a preservative.
• Enzyme Conjugate Reagent (R2): Contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with nortriptyline in Tris buffer with sodium azide as a preservative.

Here's the breakdown of the acceptance criteria and study information for the Alinity c Tricyclic Antidepressants Reagent Kit, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate predefined table for each test. Instead, the performance studies themselves imply the acceptance criteria by demonstrating successful results within expected ranges for each analytical parameter. I've synthesized these based on common analytical performance expectations and the reported findings.

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

• Precision Studies (Repeatability): 80 replicates for each of 7 concentration levels (total 560 samples) for qualitative and semi-quantitative modes.
• Precision Studies (Reproducibility): 75 replicates for each of 7 concentration levels (total 525 samples) for qualitative and semi-quantitative modes.
• Spike Recovery: 20 replicates for Low Control (225 ng/mL) and 20 replicates for High Control (375 ng/mL).
• Dilution Linearity: 5 replicates for each of 9 concentration levels (total 45 samples).
• Method Comparison and Accuracy: 50 negative and 50 positive patient specimens (total 100 patient specimens).
• Matrix Equivalency: 50 patient samples (analyzed in 2 replicates each, across 6 different plasma matrices).
• Specificity (Cross-Reactivity): Varies per compound, generally by spiking known amounts into drug-free serum.
• Interference: Low control (225 ng/mL) and high control (375 ng/mL) samples were spiked with various interfering substances.

Data Provenance: The document does not explicitly state the country of origin for the data or whether the patient specimens were retrospective or prospective. It refers to "patient specimens" without further detail on their origin or collection method.

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

The document states that the test results were "Compared to LC-MS/MS lab testing." LC-MS/MS (Liquid Chromatography/Tandem Mass Spectrometry) is generally considered the gold standard confirmatory method for drug analyses. Therefore, the ground truth was established by this highly specific and sensitive analytical technique, rather than by human expert consensus or pathology in the traditional sense. The document does not specify the number or qualifications of individuals who performed or interpreted the LC-MS/MS tests; it's assumed to be performed by qualified laboratory personnel.

4. Adjudication Method (for the test set)

Ground truth was established by LC-MS/MS, which is an objective chemical analysis method. Therefore, no human adjudication method (like 2+1 or 3+1) was used or needed for establishing the ground truth. Discordant samples were further investigated using additional LC-MS analysis to assess the root cause, indicating a scientific investigation of discrepancies rather than a consensus-based adjudication.

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

No MRMC comparative effectiveness study was done. This device is an automated clinical chemistry assay, an in vitro diagnostic (IVD) reagent kit, and not an AI-powered diagnostic imaging device involving human readers. Therefore, there's no "human readers improve with AI vs. without AI assistance" effect size to report.

6. Standalone Performance Study

Yes, a standalone performance study was done. All the analytical performance studies (Precision, Spike Recovery, Dilution Linearity, Method Comparison, Matrix Equivalency, Specificity, Interference) evaluate the performance of the Alinity c Tricyclic Antidepressants Reagent Kit (i.e., the algorithm/reagent system) independently. The results reported are the performance of the device without human interpretation affecting the primary quantitative or qualitative output of the assay.

7. Type of Ground Truth Used

The primary ground truth used for performance evaluation, particularly for method comparison and accuracy, was LC-MS/MS (Liquid Chromatography/Tandem Mass Spectrometry) results. LC-MS/MS is considered a definitive confirmatory method for drug concentrations.

8. Sample Size for the Training Set

The document does not provide information about a "training set" in the context of machine learning or AI. This device is described as a "homogeneous enzyme immunoassay" using "polyclonal antibodies." This indicates a traditional biochemical assay technology, not a machine learning model that requires a dedicated training set. Therefore, this question is not applicable to the technology described.

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

As noted in point 8, this device does not appear to be an AI/ML-based system requiring a training set. If there were any internal development or calibration processes that involved data, the document does not specify them or their ground truth establishment. For traditional IVD assays, performance is typically validated against reference methods and known standards.

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The CEDIATM Heroin Metabolite (6-AM) Assay is a homogeneous enzyme immunoassay for the in vitro qualitative and or semi-quantitative determination of the presence of heroin metabolite (6-AM) in human urine at a cut-off concentration of 10 ng/mL. The assay is intended to be used in laboratories and provides a rapid analytical screening procedure to detect 6-Acetylmorphine in human urine. The assay is designed for use with a number of clinical chemistry analyzers. This product is intended to be used by trained professionals only.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

CEDIA technology uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ßgalactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously re-associate to form fully active enzymes that, in the assay format, cleave a substrate. This generates a color change that can be measured spectrophotometrically.

CEDIA™ Heroin Metabolite (6-AM) Assay is supplied as a two liquid and two lyophilized reagent kit homogeneous enzyme immunoassay. The assay uses an antibody that is specific for 6-Acetylmorphine and cross reacts with Heroin. The assay has minimal cross reactivity to structurally related and unrelated compounds. In the assay, analyte in the sample competes with analyte coniugated to one inactive fragment of B-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjuqated on the inactive fragment, inhibiting the reassociation of inactive ß- galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of drug present in the sample.

The provided FDA 510(k) summary for the Microgenics Corporation CEDIA™ Heroin Metabolite (6-AM) Assay (K231007) does not contain the detailed information necessary to fully address all aspects of your request. This document is a summary of the device's substantial equivalence to a predicate device, not a complete study report.

Specifically, the document does not contain details regarding the study design, sample sizes for test and training sets, data provenance, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance. The studies mentioned are focused on analytical performance characteristics (precision, spike recovery, dilution linearity, method comparison, specificity, stability) relevant to an in vitro diagnostic assay, rather than a typical AI/ML device assessment.

However, I can extract the available information regarding acceptance criteria and reported device performance:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size:
  • For Precision / Spike Recovery in Qualitative Mode: "All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL samples" were used. This indicates 20 replicates for each of these two concentrations, plus presumably samples for the 10 ng/mL cutoff for comparison. The total number of individual samples is not explicitly stated beyond these replicates for specific concentrations.
  • For Method Comparison: No specific number for the test set is provided, only percentages of agreement.
  • For Specificity (Interference): "tested concentrations" are mentioned, but the number of samples is not provided.
  • For Reagent Stability: "one lot" for on-board, reconstituted, and open vial stability, and "three lots" for real-time stability.
• Data Provenance: Not specified (e.g., country of origin, retrospective or prospective). The studies appear to be laboratory-based analytical performance studies. The "human urine" matrix is mentioned, indicating human samples were used.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the document. For in vitro diagnostic devices like this assay, "ground truth" is typically established through a reference method (e.g., LC-MS/MS or GC/MS for drug levels) not by human experts interpreting images or other complex data.

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

This information is not applicable/not provided. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation of medical images or other subjective data where consensus among experts is needed. For an immunoassay, the "ground truth" is determined by a quantitative chemical method, not by expert consensus.

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

This information is not applicable/not provided. An MRMC study is relevant for AI-powered diagnostic tools where human readers (e.g., radiologists) interact with or are assisted by the AI. This device is an in vitro diagnostic immunoassay, not an AI imaging or diagnostic algorithm designed to assist human readers.

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

This information is not applicable/not provided in the context of AI algorithms. This device is an immunoassay, and its "standalone performance" is what is described in the precision, spike recovery, dilution linearity, and specificity sections. It's an automated chemical analysis, not an AI algorithm performing a task without human intervention in an AI/ML sense.

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

The document mentions that for confirmation, "A more specific alternative chemical method must be used...Gas chromatography/mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method." This indicates that confirmatory chemical analysis (LC-MS/MS or GC/MS) serves as the "ground truth" or reference method for determining the presence and concentration of 6-Acetylmorphine in urine samples.

8. The sample size for the training set

This information is not provided. The development of an immunoassay may involve optimization and calibration with a set of samples, but these are typically not referred to as a "training set" in the context of machine learning.

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

This information is not provided. Similar to point 8, the concept of a "training set" and its "ground truth" establishment as used in AI/ML is not directly applicable or documented for this type of in vitro diagnostic device in this summary. The development process would involve optimizing the assay's chemical components and reaction parameters using well-characterized samples.

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The DRI™ Tricyclics Serum Tox Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semiquantitative determination of the presence of tricyclic antidepressants (TCAs) in human serum, plasma, or urine of patients at a cutoff concentration of 300 ng/mL in patients suspected of drug overdose.

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

The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

For In Vitro Diagnostic Use Only.

The DRI™ Tricyclics Serum Tox Assay is a homogeneous enzyme immunoassay using ready to-use liquid reagents. Specific tricyclic antibodies were used to detect most tricyclic antidepressants in serum, plasma, or urine. The test is based on the competition of an enzyme, glucose-6-phosphate dehydrogenase (G6PDH), labeled-drug and the drug from the sample for a fixed amount of specific antibody binding sites. In the absence of the drug from the sample, the specific antibody binds the enzyme-labeled drug and the enzyme activity is inhibited. This phenomenon creates a direct relationship between drug concentration in the sample and the enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

The DRI™ Tricyclics Serum Tox assay is supplied as a two liquid reagent kit (Reagent A and Reagent E). Thev are bottled separately within the same kit, see details below:

• Antibody/Substrate Reagent (Reagent A): Contains polyclonal anti-tricyclics . antibodies (sheep), glucose-6- phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as a preservative.
• Enzyme Conjugate Reagent (Reagent E): Contains glucose-6-phosphate ● dehydrogenase (G6PDH) labeled with nortriptyline in Tris buffer with sodium azide as a preservative.

The provided document describes the analytical performance of the DRI™ Tricyclics Serum Tox Assay. It details various studies conducted to demonstrate its performance characteristics, but it does not explicitly state specific pass/fail acceptance criteria for each test. Instead, it presents the results of each study, implying that these results met the internal criteria used by the manufacturer for demonstrating sufficient performance and substantial equivalence to the predicate device.

Here's an analysis of the provided information, addressing your points where possible, and noting when the information is unavailable:

1. A table of acceptance criteria and the reported device performance

As mentioned, explicit acceptance criteria (e.g., "Accuracy must be >95%") are not stated in this document. The tables below summarize the reported device performance for several key analytical studies. The implication is that these reported performances were deemed acceptable for the 510(k) clearance.

• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 80/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 10/70 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/80 (Negative/Positive)

Semi-Quantitative Mode (n=80 for each concentration):

• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 80/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 19/61 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/80 (Negative/Positive)
  | Qualitative Mode (n=80 for each concentration):
• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 80/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 68/12 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/80 (Negative/Positive)

Semi-Quantitative Mode (n=80 for each concentration):

• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 80/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 73/7 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/80 (Negative/Positive)
  |
  | Precision (Reproducibility) | Qualitative Mode (n=75 for each concentration):
• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 75/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 30/45 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/75 (Negative/Positive)

Semi-Quantitative Mode (n=75 for each concentration):

• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 75/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 29/46 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/75 (Negative/Positive)
  | Qualitative Mode (n=75 for each concentration):
• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 75/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 61/14 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/75 (Negative/Positive)

Semi-Quantitative Mode (n=75 for each concentration):

• 0 ng/mL to 225 ng/mL (-100% to -25% Cutoff): 75/0 (Negative/Positive)
• 300 ng/mL (100% Cutoff): 66/9 (Negative/Positive)
• 375 ng/mL to 600 ng/mL (+25% to +100% Cutoff): 0/75 (Negative/Positive)
  |
  | Spike Recovery | Low Control (225 ng/mL, n=20): All 20 Negative (Below Cutoff)
  High Control (375 ng/mL, n=20): All 20 Positive (Above Cutoff) | Low Control (225 ng/mL, n=20): All 20 Negative (Below Cutoff)
  High Control (375 ng/mL, n=20): All 20 Positive (Above Cutoff) |
  | Dilution Linearity (Recovery)| Range 96-115% for expected values 125 ng/mL to 1000 ng/mL (average of 5 replicates) | Range 94-118% for expected values 125 ng/mL to 1000 ng/mL (average of 5 replicates) |
  | Method Comparison (Accuracy) | Qualitative Mode (n=117):
• % Negative Sample Agreement: 98% (60/61)
• % Positive Sample Agreement: 100% (56/56)
• % Total Sample Agreement: 99% (116/117)
  Semi-Quantitative Mode (n=117):
• % Negative Sample Agreement: 97% (59/61)
• % Positive Sample Agreement: 100% (56/56)
• % Total Sample Agreement: 98% (115/117) | Qualitative Mode (n=100):
• % Negative Sample Agreement: 96% (48/50)
• % Positive Sample Agreement: 98% (49/50)
• % Total Sample Agreement: 97% (97/100)
  Semi-Quantitative Mode (n=100):
• % Negative Sample Agreement: 96% (48/50)
• % Positive Sample Agreement: 98% (49/50)
• % Total Sample Agreement: 97% (97/100) |
  | Matrix Equivalency | Serum: 50 patient samples total (25 positive, 25 negative). Full agreement for K2 EDTA Plasma, K3 EDTA Plasma, Lithium Heparin Plasma, Sodium Citrate Plasma, Potassium Oxalate Plasma across qualitative and semi-quantitative modes.
  Sodium Heparin Plasma: 45 patient samples (25 positive, 20 negative). Full agreement across qualitative and semi-quantitative modes. | Not applicable (serum comparison) |
  | Interference | Spiking endogenous/exogenous/physiological substances at high concentrations into low and high controls (225 ng/mL and 375 ng/mL) showed accurate detection of controls (negative for low, positive for high), indicating no interference. (See Table 20 for list of compounds and concentrations tested). | Spiking endogenous/exogenous/physiological substances and pH variations (pH 3-11) at high concentrations into low and high controls (225 ng/mL and 375 ng/mL) showed accurate detection of controls (negative for low, positive for high), indicating no interference. (See Table 21 for list of compounds and concentrations tested). Specific gravity (1.004-1.030) also showed no interference. |
  | Specificity (Cross-Reactivity) | Extensive tables (Table 16, 18, 20) are provided listing cross-reactivity percentages for numerous structurally related and unrelated compounds in serum. The study demonstrated cross-reactivity for various TCA drugs and metabolites (e.g., Amitriptyline 100%, Desipramine 120%, Imipramine 157.9%). Minimal to no cross-reactivity (

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The Alinity c Cocaine assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL on the Alinity c analyzer.

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

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-to-use liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine samplefor a fixed amount of specific antibody binding sites. In the presence of free drug fromthe sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

The assay consists of reagents (A and E).

Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6- phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.

Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.

The provided text describes the analytical performance studies for the DRI Cocaine Metabolite Assay, an in vitro diagnostic device, rather than an AI-powered medical device requiring human-in-the-loop studies or expert consensus for ground truth. Therefore, many of the requested elements for AI/ML device studies (such as MRMC studies, number of experts for ground truth, adjudication methods, training set information) are not applicable to this submission.

However, I can extract information related to the acceptance criteria and performance of this in vitro diagnostic device.

Here's a breakdown based on the provided document:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the results presented in the analytical performance studies. The device is expected to accurately categorize samples as negative or positive relative to defined cutoffs (150 ng/mL or 300 ng/mL) and demonstrate good precision, linearity, and minimal interference.

Table of Acceptance Criteria (Implied) and Reported Device Performance

• Below cutoff (-100% to -25%): 100% Negative (e.g., 120/0 or 119/0)
• Above cutoff (+25% to +100%): 100% Positive (0/120 or 0/119)
• At cutoff (150 ng/mL): Qualitative: 76/44 (N/P), Semi-Quantitative: 73/47 (N/P)
  300 ng/mL cutoff:
• Below cutoff (-100% to -25%): 100% Negative (e.g., 120/0 or 119/0)
• Above cutoff (+25% to +100%): 100% Positive (0/120)
• At cutoff (300 ng/mL): Qualitative: 44/76 (N/P), Semi-Quantitative: 42/77 (N/P) |
  | Spike Recovery | Samples spiked below cutoff should be negative; samples spiked above cutoff should be positive. | 150 ng/mL cutoff:
• 112.5 ng/mL (below C/O): 25/25 Negative
• 187.5 ng/mL (above C/O): 25/25 Positive
  300 ng/mL cutoff:
• 225 ng/mL (below C/O): 25/25 Negative
• 375 ng/mL (above C/O): 25/25 Positive |
  | Linearity | Observed concentrations should be within an acceptable recovery range of expected concentrations across the assay range. | Excellent linearity demonstrated over the range 0 to 1032.2 ng/mL. Percent recovery from 95.7% to 111.4%. |
  | Method Comparison (Accuracy) | High agreement (concordance) with the confirmatory method (LC-MS/MS). Discordant results should be minimal and explainable. | 150 ng/mL cutoff (Semi-Quantitative & Qualitative):
• Agreement among Positives: 100% (51/51)
• Agreement among Negative: 98% (49/50)
• 1 discordant result (Device: Positive, LC-MS/MS: 134 ng/mL, which is below 150 ng/mL cutoff)
  300 ng/mL cutoff (Semi-Quantitative & Qualitative):
• Agreement among Positives: 100% (50/50)
• Agreement among Negative: 96% (48/50)
• 2 discordant results (Device: Positive, LC-MS/MS: 268 ng/mL and 211 ng/mL, both below 300 ng/mL cutoff) |
  | Specificity (Cross-Reactivity) | Minimal cross-reactivity with structurally related or unrelated compounds at specified concentrations. | Cocaine and metabolites:
• Benzoylecgonine: 100%
• Cocaine: 0.6%
• Cocaethylene: 0.5%
• Ecgonine: 0.17-0.19%
• Ecgonine Methyl Ester:

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The CEDIA Heroin Metabolite (6-AM) Assay is a homogeneous enzyme immunoassay for the in vitro qualitative and/or semi-quantitative determination of the presence of heroin metabolite (6-AM) in human urine at a cut-off concentration of 10 ng/mL. The assay is intended to be used in laboratories and provides a rapid analytical screening procedure to detect 6-Acetylmorphine in human urine. The assay is designed for use with a number of clinical chemistry analyzers. This product is intended to be used by trained professionals only.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only

The assay consists of buffers (1 and 2) and lyophilized reagents (1a and 2a). The components include mouse monoclonal antibodies to 6-Acetylmorphine, recombinant microbial "enzyme donor" - 6-Acetylmorphine conjugate, "enzyme acceptor", chlorophenol red ß-Dgalactopyranoside, stabilizers and preservatives.

Here's a summary of the acceptance criteria and study details for the CEDIA Heroin Metabolite (6-AM) Assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

• 0 to 7.5 ng/mL (below cutoff): 80/0 (Negative/Positive) determinations.
• 10 ng/mL (at cutoff): 25/55 (Negative/Positive) determinations.
• 12.5 to 20 ng/mL (above cutoff): 0/80 (Negative/Positive) determinations.

Semi-Quantitative Mode:

• 0 to 7.5 ng/mL (below cutoff): 80/0 (Negative/Positive) determinations.
• 10 ng/mL (at cutoff): 46/34 (Negative/Positive) determinations.
• 12.5 to 20 ng/mL (above cutoff): 0/80 (Negative/Positive) determinations. |
  | Spike Recovery | Qualitative: No ± 2SD overlap between samples below, at, and above the cutoff. All replicates of spiked negative and positive controls should be accurately detected.
  Semi-quantitative: Spiked samples recover within 80-120% of nominal values. | Qualitative Mode: No ± 2SD overlap between 7.5 ng/mL, 10 ng/mL, and 12.5 ng/mL. All 20 replicates of 7.5 ng/mL were Negative, and all 20 replicates of 12.5 ng/mL were Positive, compared to 10 ng/mL.
  Semi-Quantitative Mode: Spiked samples recovered within 80-120% of nominal values (as seen in the Analytical Recovery table). |
  | Analytical Recovery and Dilution Linearity | Semi-quantitative mode: Demonstrates ability for sample dilution and QC across the assay range, with acceptable percent recovery. | Average Recovery (%) ranged from 97.3% to 115.6% for target concentrations from 0 to 20 ng/mL. Range of Recovery (%) was also provided. |
  | Method Comparison and Accuracy | High concordance (suggesting 100%) between the immunoassay and a confirmatory method (LC-MS/MS) for patient samples across various concentration ranges. | Qualitative & Semi-Quantitative Modes: Overall concordance between LC-MS/MS and CEDIA Heroin Metabolite (6-AM) Assay was 100% for the 103 samples tested. |
  | Specificity (Cross-reactivity with Metabolites) | 6-Acetylmorphine shows 100% cross-reactivity and heroin shows appropriate cross-reactivity (e.g., in this case, 8.3%). | 6-Acetylmorphine: 100% cross-reactivity at 10 ng/mL.
  Heroin: 8.3% cross-reactivity at 120 ng/mL. |
  | Specificity (Cross-reactivity with Structurally Related/Unrelated Compounds) | Structurally related or unrelated compounds should exhibit minimal cross-reactivity (e.g.,

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The CEDIA™ Benzodiazepine Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzodiazepines in human urine at a cutoff concentration of 200 ng/mL.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used 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 drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

CEDIA™ technology uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments, Enzyme acceptor (EA) and Enzyme Donor (ED). These fragments spontaneously re-associate to form fully active enzyme that, in the assay format, cleaves a substrate. This generates a color change that can be measured spectrophotometrically.

The assay consists of buffers (1 and 2) and lyophilized reagents (1a and 2a). The components include sheep polyclonal anti-benzodiazepine antibody, recombinant microbial "enzyme donor'' - benzodiazepine conjugate, "enzyme acceptor", chlorophenol red ß-Dgalactopyranoside, stabilizers and preservatives. Add ß-glucuronidase enzyme to the reconstituted EA solution before using the assay. All specimens must be tested with ßglucuronidase enzyme. This enzyme will hydrolyze the glucuronidated metabolites of benzodiazepines in the samples, thereby enabling the detection of benzodiazepine glucuronides.

The provided text describes the analytical performance of the CEDIA™ Benzodiazepine Assay, an in vitro diagnostic device, and does not contain information related to an AI/ML-based device. Therefore, a direct response to the request for acceptance criteria and study details for an AI/ML device is not possible based on the provided text.

However, I can extract and present the acceptance criteria and the reported device performance for this in vitro diagnostic device based on the provided document.

Acceptance Criteria and Study for CEDIA™ Benzodiazepine Assay (In Vitro Diagnostic Device)

The CEDIA™ Benzodiazepine Assay is an in vitro diagnostic device for the qualitative and/or semi-quantitative determination of benzodiazepines in human urine. The document details its analytical performance studies to establish substantial equivalence to a predicate device, not an AI/ML-based system.

Here's a summary of the acceptance criteria (implied by the reported precision and accuracy goals) and the reported device performance from the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for precision, accuracy, or other analytical performance metrics. Instead, it presents results intended to demonstrate that the device performs adequately and is substantially equivalent to a predicate device. For the purpose of this response, I will interpret the reported performance as meeting the implicit acceptance criteria for an in vitro diagnostic assay of this type.

Cut-off Concentration: 200 ng/mL

Qualitative Mode:
Agreement among Positives: 100% (68/68)
Agreement among Negatives: 93% (56/60)

Semi-Quantitative Mode:
Agreement among Positives: 99% (67/68)
Agreement among Negatives: 93% (56/60) |
| Specificity (Cross-reactivity) | Minimal to no interference from structurally unrelated compounds. Relevant benzodiazepines and metabolites should show expected reactivity. | Structurally unrelated compounds (e.g., Acetaminophen, Amphetamine, Caffeine, Codeine etc. at high concentrations up to 100,000 ng/mL) showed no significant cross-reactivity, maintaining expected results for spiked low/high controls. Data provided for 30+ benzodiazepines and metabolites, showing varying cross-reactivity percentages. |
| Interference (pH, Endogenous/Exogenous Substances) | No interference from common physiological substances or varying pH levels. | Various compounds (e.g., Acetone, Ascorbic Acid, Glucose, Hemoglobin, Human Serum Albumin, Urea) and pH levels (3-11) showed no interference, maintaining expected results for spiked low/high controls. |
| Specific Gravity Interference | No interference from varying specific gravity of urine samples. | Urine samples with specific gravity from 1.002 to 1.029 showed no interference, maintaining expected results for spiked low/high controls. |

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

• Precision Study:

  • Samples were tested in replicates of 2, twice per day for 20 days.
  • Total n=80 for each spiked concentration level (0 to 400 ng/mL).
  • Data Provenance: Not explicitly stated, but the study was performed at the manufacturer's site. "Drug free urine" was used for spiking. It is implied to be laboratory-controlled samples, not patient data from a specific country or retrospective/prospective collection.

• Spike Recovery Study:

  • 20 replicates for each concentration (150 ng/mL and 250 ng/mL).
  • Data Provenance: "Drug free urine" was used for spiking. Implied laboratory-controlled samples.

• Method Comparison and Accuracy Study:

  • Sample Size: One hundred and twenty-eight (128) samples.
  • Data Provenance: Not explicitly stated. The samples were "treated with ß-glucuronidase reagent prior to analysis". This suggests potentially patient-derived urine samples, but their origin (country, retrospective/prospective collection) is not mentioned.

• Specificity (Cross-reactivity) & Interference Studies:

  • Samples made by adding known amounts of compounds to "drug-free negative urine" or "Oxazepam spiked" urine.
  • Data Provenance: Laboratory-controlled samples.

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

Not applicable for this type of in vitro diagnostic device study. The "ground truth" (or reference method) for the method comparison study was established by Liquid Chromatography/tandem mass spectrometry (LC-MS/MS), which is a highly accurate chemical analytical method. It does not involve human expert interpretation in the way AI/ML systems for medical imaging, for example, would.

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

Not applicable. Ground truth was established by LC-MS/MS, an objective chemical analytical method, not by human expert consensus 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 in vitro diagnostic assay, not an AI/ML-based device that would assist human readers/operators in interpretation. Its performance is measured directly against a reference analytical method.

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

Yes, in the context of an IVD, the CEDIA™ Benzodiazepine Assay's performance is inherently standalone in the sense that the assay's output (positive/negative/concentration) is directly measured and compared against the LC-MS/MS reference method. There is no human interpretative step within the 'device' itself, nor is its primary purpose to augment human interpretation.

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

The ground truth for the method comparison study was Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) results, which is a gold standard chemical analytical method for drug concentration determination.

8. The sample size for the training set

Not applicable. This document describes an in vitro diagnostic assay, which is a chemical and biological reagent-based system, not an AI/ML algorithm that requires a "training set" in the computational sense. Its formulation and calibration are based on chemical principles and standard laboratory practices.

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

Not applicable, as there is no "training set" for this type of device. The assay is developed and optimized as a chemical system.

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The QMS Plazomicin Immunoassay is intended for the quantitative determination of plazomicin in human K2-EDTA plasma on automated clinical chemistry analyzers. The assay results obtained should only be used as an aid in the management of patients with complicated urinary tract infection (cUTI) receiving plazomicin therapy.

The assay should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures.

The OMS Plazomicin Immunoassay system is a homogeneous assay utilizing particle agglutination technology and it is based on the competitive binding principle. The assay consists of liquid ready-to-use reagents R1 (anti-plazomicin mouse monoclonal antibody) and R2 (plazomicin-coated microparticles).

Here's a breakdown of the acceptance criteria and the study proving the device's performance, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are not explicitly laid out as a numbered list with specific thresholds before the results are presented. Instead, the document describes the types of studies conducted to evaluate performance, and the results of those studies demonstrate that the device meets the "clinically appropriate" standards as determined by the FDA. The special controls outlined in Section P provide a retrospective view of what was deemed acceptable.

Therefore, the table below consolidates the implicit acceptance criteria based on the special controls and the corresponding reported performance.

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

• Test Set (Analytical Studies):

  • Precision (Internal):
    • Quality Control (QC) and Spiked samples: n=80 each (2 replicates/run, 2 runs/day, 20 days).
    • Patient Plasma Pools: n=20 each (2 replicates/run, 2 runs/day, 5 days).
  • Precision (Multi-Laboratory):
    • QC and Spiked samples: n=240 each (n=80 per site x 3 sites).
    • Patient Pools: n=60 each (n=20 per site x 3 sites).
  • Linearity: 9 levels of samples, tested in 5 replicates in a single run.
  • Analytical Recovery: Each sample panel analyzed over 5 days with 4 replicates/day (total 20 measurements per sample).
  • Detection Limit (LoB, LoD, LoQ): Specific sample numbers for LoB/LoD/LoQ are redacted (b)(4). LoB used (b)(4) K2-EDTA samples and LoD used (b)(4) blank plasma K2-EDTA samples.
  • Method Comparison: 134 K2-EDTA plasma samples from patients taking plazomicin.
  • Interference (Endogenous/Exogenous): Not explicitly stated, but implies a sufficient number of spiked samples to test the indicated concentrations.

• Data Provenance:

  • Country of Origin: Not explicitly stated, but the multi-laboratory precision study and method comparison study imply a multi-site approach, possibly within a single country or across different countries, but this is not detailed.
  • Retrospective or Prospective: Most of the analytical performance studies (precision, linearity, recovery, detection limits, interference) appear to be prospective laboratory studies using prepared or collected samples. The patient samples used for precision and method comparison are collected from patients taking plazomicin, indicating a real-world context for some of the samples. The clinical trial data for plazomicin efficacy/nephrotoxicity (mentioned under "Clinical Studies") was retrospective regarding the device's evaluation, as TDM was not used to adjust dosing during that trial, but the data was later correlated.

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

• Number of Experts: This is a quantitative immunoassay, not an imaging device requiring expert reader interpretation. Therefore, the concept of "experts establishing ground truth" in the typical sense (e.g., radiologists reviewing images) does not directly apply.
• Qualifications of Experts: The ground truth for this device is established through:
  • Reference Methods: The primary ground truth for the device's accuracy and traceability is a validated LC-MS/MS method. Personnel operating and validating LC-MS/MS are highly trained laboratory professionals with expertise in mass spectrometry and analytical chemistry, though their specific qualifications (e.g., years of experience, certifications) are not detailed in this document.
  • Gravimetric Preparation: Plazomicin reference calibrators are gravimetrically prepared, meaning their concentration is determined by precise weighing, which implies a fundamental chemical and metrological expertise.
  • CLSI Guidelines: The studies follow CLSI (Clinical and Laboratory Standards Institute) guidelines, which are established by consensus among experts in laboratory medicine.

4. Adjudication Method for the Test Set

• Since the ground truth is established by reference methods (LC-MS/MS, gravimetric preparation) and not by subjective expert interpretation, there is no "adjudication method" in the sense of resolving discrepancies between multiple human readers. The analytical methods themselves have defined reconciliation processes, but it's not a multi-reader adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

• No, an MRMC study was NOT done. This device is a quantitative immunoassay, not an AI-powered diagnostic tool that assists human readers in interpreting complex data like medical images. Therefore, the concept of human readers improving with AI assistance is not applicable here.

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

• Yes, in essence, standalone performance was evaluated. The QMS Plazomicin Immunoassay is an automated laboratory test. Its performance characteristics (precision, linearity, accuracy against LC-MS/MS, detection limits, interference) are all measures of its intrinsic, standalone capability to quantify plazomicin in a sample. There isn't a "human-in-the-loop" component to its analytical function; rather, humans use the results obtained from the automated device.

7. The Type of Ground Truth Used

The ground truth used for evaluating the QMS Plazomicin Immunoassay's performance includes:

• Reference Measurement Procedure: A validated LC-MS/MS method was used as the comparator for method comparison studies, serving as the "gold standard" for quantifying plazomicin.
• Gravimetric Preparation: For calibrators and spiked samples, the known concentration derived from gravimetric preparation (weighing out precise amounts of plazomicin) served as the ground truth.
• Clinical Outcomes Data (Indirectly for clinical utility, not analytical performance): The clinical trial data (retrospectively analyzed post-drug approval) provided evidence for the correlation between plazomicin trough levels and nephrotoxicity, which established the clinical need and medical decision points for the assay, but not the direct analytical accuracy of the device itself.

8. The Sample Size for the Training Set

• Not Applicable in the traditional machine learning sense. This document describes a traditional in-vitro diagnostic (IVD) device (a chemical immunoassay), not an AI/Machine Learning algorithm that requires a "training set" to learn from data. The device's operational parameters (e.g., reagant concentrations, instrument settings) are determined through development and optimization processes, not by training on a large dataset in the way an AI model would be.

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

• Not Applicable. As this is not an AI/ML device, there is no "training set" or corresponding ground truth establishment process in that context. The "ground truth" for the device's development primarily relies on established principles of analytical chemistry, reagent formulation, and calibration against reference methods like LC-MS/MS and gravimetric standards.

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The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used 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. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-to-use liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

The assay consists of reagents (A and E).

Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.

Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.

The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at cutoff concentrations of either 150 ng/mL or 300 ng/mL. The study performed aims to demonstrate the analytical performance of the device and its substantial equivalence to the predicate device, Cocaine Metabolite Enzyme Immunoassay (K960187).

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for agreement percentages (e.g., "must be >95%"). However, the reported performance demonstrates 100% agreement with the reference method (LC-MS/MS) for both positive and negative samples at both cutoff levels in the method comparison study. The precision studies also show consistent determination of positive and negative results at concentrations significantly above and below the cutoff, with expected mixed results at the cutoff itself.

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