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Amphetamines II (AMPII) is an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines in human urine on COBAS INTEGRA systems at cutoff concentrations of 300 ng/mL, 500 ng/mL and 1000 ng/mL when calibrated with a-methamphetamine. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC/MS).

Amphetamines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method.1 Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

The Amphetamines II test is an immunoassay for use on automated clinical chemistry analyzers. The device consists of two wet reagents; a soluble drug-conjugate, and an antibody-bound microparticle solution. During the assay, in the absence of sample drug in urine, soluble drug-conjugates bind to antibody-bound microparticles, causing the formation of particle aggregates. When a urine sample contains the drug in question, this drug competes with the drug derivative conjugate for microparticle-bound antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The rate of absorbance change is proportional to the concentration of drug in the sample. Calibrators, ranging in concentration from 0-5000 ng/mL depending on cutoff and test mode, are run with the assay. Concentrations of controls and unknowns are calculated from the standard curve in semi-quantitative mode. Results for controls or calibrators are determined as preliminary positive or negative relative to the cutoff in qualitative mode.

C.f.a.s. DAT Qualitative Clinical, C.f.a.s. DAT Qualitative Plus, C.f.a.s. DAT Qualitative Plus Clinical, Preciset DAT Plus I Calibrators, and Preciset DAT Plus II Calibrators are ready to use, multianalyte calibrators prepared by the quantitative addition of drug or drug metabolite to drug-free human urine.

Control Set DAT I, II, and III, and Control Set DAT Clinical are ready to use multianalyte controls prepared by the quantitative addition of drug or drug metabolite to drug-free urine.

Here's an analysis of the provided text regarding the Amphetamines II Assay, structured to address your specific points:

The provided document describes the Amphetamines II Assay for Integra Family of Analyzers, an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines in human urine. The device's performance is primarily evaluated through precision and accuracy studies against Gas Chromatography/Mass Spectrometry (GC/MS).

1. Table of Acceptance Criteria and Reported Device Performance

The general acceptance criteria for this type of immunoassay are implicit in the performance studies: accurate detection of amphetamines/methamphetamines in urine relative to established cutoffs, with good precision and minimal interference from other substances. The detailed criteria would typically be established internally by the manufacturer and submitted to regulatory bodies.

Here's a summary of the stated performance, interpreted against general expectations for such assays:

• 300 ng/mL Cutoff (MAMP): 84/84 Negative at zero, -75%, -50% of cutoff. 83/84 Negative at -25% of cutoff. 27/84 Negative, 57/84 Positive at cutoff. 84/84 Positive at +25%, +50%, +75%, +100% of cutoff.
• 500 ng/mL Cutoff (MAMP): 84/84 Negative at zero, -75%, -50% of cutoff. 84/84 Negative at -25% of cutoff. 28/84 Negative, 56/84 Positive at cutoff. 84/84 Positive at +25%, +50%, +75%, +100% of cutoff.
• 1000 ng/mL Cutoff (MAMP): 84/84 Negative at zero, -75%, -50%, -25% of cutoff. 13/84 Negative, 71/84 Positive at cutoff. 84/84 Positive at +25%, +50%, +75%, +100% of cutoff.
• 300 ng/mL Cutoff (AMP): 84/84 Negative at zero, -75%, -50% of cutoff. 83/84 Negative at -25% of cutoff. 2/84 Negative, 82/84 Positive at cutoff. 84/84 Positive at +25%, +50%, +75%, +100% of cutoff.
• 500 ng/mL Cutoff (AMP): 84/84 Negative at zero, -75%, -50% of cutoff. 82/84 Negative, 2/84 Positive at -25% of cutoff. 6/84 Negative, 78/84 Positive at cutoff. 84/84 Positive at +25%, +50%, +75%, +100% of cutoff.
• 1000 ng/mL Cutoff (AMP): 84/84 Negative at zero, -75%, -50% of cutoff. 82/84 Negative, 2/84 Positive at -25% of cutoff. 7/84 Negative, 77/84 Positive at cutoff. 1/84 Negative, 83/84 Positive at +25% of cutoff. 84/84 Positive at +50%, +75%, +100% of cutoff.

Semiquantitative Mode (SD, CV% ranges reported):

• For MAMP at 300, 500, 1000 ng/mL cutoffs:
  • Repeatability (within-run) CV% for zero to +100% of cutoff generally good (e.g., 5.7%-95.4% for 300 ng/mL, with highest CVs at very low concentrations).
  • Intermediate Precision (total) CV% for zero to +100% of cutoff also generally good (e.g., 6.5%-123.8% for 300 ng/mL, with highest CVs at very low concentrations).
• For AMP at 300, 500, 1000 ng/mL cutoffs:
  • Repeatability (within-run) CV% generally good (e.g., 5.3%-110.0% for 300 ng/mL).
  • Intermediate Precision (total) CV% also generally good (e.g., 6.5%-135.7% for 300 ng/mL). |
    | Accuracy (Agreement with GC/MS) | MAMP (d-methamphetamine):
• Qualitative & Semiquantitative Assays:
  • 100% agreement for High Positive by GC/MS (greater than +50% of cutoff) across all cutoffs (300, 500, 1000 ng/mL).
  • 100% agreement for Near Cutoff Positive by GC/MS (between cutoff and +50%) across all cutoffs.
  • For Low Negatives (below cutoff) / Near Cutoff Negative (between -50% and cutoff):
    • 300 ng/mL Cutoff: 90% (Qualitative & Semiquantitative).
    • 500 ng/mL Cutoff: 91% (Qualitative & Semiquantitative).
    • 1000 ng/mL Cutoff: 90% (Qualitative & Semiquantitative).

AMP (d-amphetamine):

• Qualitative & Semiquantitative Assays:
  • 100% agreement for High Positive by GC/MS (greater than +50% of cutoff) across all cutoffs.
  • 100% agreement for Near Cutoff Positive by GC/MS (between cutoff and +50%) across all cutoffs.
  • For Low Negatives (below cutoff) / Near Cutoff Negative (between -50% and cutoff):
    • 300 ng/mL Cutoff: 92.5% (Qualitative & Semiquantitative).
    • 500 ng/mL Cutoff: 92.5% (Qualitative & Semiquantitative).
    • 1000 ng/mL Cutoff: 97.5% (Qualitative), 95% (Semiquantitative). |
      | Analytical Specificity / Cross-reactivity | A wide range of structurally similar compounds (e.g., MDMA, MDA, MDEA, BDB, l-Methamphetamine, l-Amphetamine) show varying degrees of cross-reactivity, with some "designer drugs" showing higher cross-reactivity than others (e.g., MDMA at 264% at 300 ng/mL MAMP equivalent). Most other common drugs/substances (e.g., acetaminophen, ibuprofen, caffeine, opiates, benzodiazepines) show either no significant interference or proper recovery of spiked samples at specified high concentrations (100,000 ng/mL). |
      | Interference from Common Substances | No interference observed from high concentrations of common urine components (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Human serum albumin, Oxalic Acid, Sodium Chloride, Urea) for both qualitative and semiquantitative modes across all cutoffs when spiked with d-methamphetamine or d-amphetamine at -25% and +25% of cutoff. |
      | pH and Specific Gravity Interference | No control cross-overs for specific gravities from 1.001 to 1.034. ≤ 5% cross-overs for pH ranging from 4.5 to 8.0. |

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

• Precision Test Set Sample Size:
  • For each cutoff (300, 500, 1000 ng/mL) and each drug (d-methamphetamine, d-amphetamine): 9 concentrations were tested.
  • Each concentration was tested in 2 replicates per run, 2 runs per day for 21 days.
  • Total N = 84 determinations per concentration level. (e.g., 9 concentrations * 84 determinations = 756 total determinations per drug per cutoff for precision).
  • Data Provenance: "9 samples obtained from a human urine sample pool" for initial spiking. The source of this urine pool is not specified (e.g., country of origin). This was a retrospective study measuring inherent characteristics of the assay.
• Accuracy Test Set Sample Size:
  • Negative Samples: 36 urine samples confirmed negative by GC/MS.
  • Positive Samples: 36 samples confirmed positive by GC/MS (containing d-methamphetamine or d-amphetamine).
  • Near Cutoff Samples: For each cutoff, 4 negative near cutoff samples and 4 positive near cutoff samples were assayed.
  • 4 additional unaltered samples (d-methamphetamine, 85-204 ng/mL) evaluated with 500 ng/mL cutoff.
  • Data Provenance: "samples obtained from a clinical laboratory" and "unaltered near cutoff samples." Geographic origin is not specified. This was a retrospective study comparing the device to a gold standard.
• Analytical Specificity Test Set Sample Size: Not explicitly stated as a count of individual samples, but inhibition curves were generated for each of the many tested compounds.
• Interference Test Set Sample Size: Not explicitly stated as a count of individual samples, but various compounds were added to urine pools at specified concentrations. This appears to be a laboratory retrospective study.

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

• The ground truth for the test set (accuracy study) was established by Gas Chromatography/Mass Spectrometry (GC/MS).
• This method is explicitly stated as "the preferred confirmatory method" and the device's traceability is stated as "Traceability: This method has been standardized against GC/MS."
• There is no mention of human expert involvement in establishing the ground truth; it relies on the analytical capabilities of GC/MS. Therefore, qualifications of human experts for ground truth are not applicable in this context.

4. Adjudication Method for the Test Set

• Adjudication methods like 2+1 or 3+1 typically apply to studies where human readers interpret data, and discrepancies need to be resolved.
• In this context, the device's results are compared directly to the quantitative results from GC/MS. There is no human interpretation of the device's output or a need for expert adjudication of "truth" beyond the GC/MS result itself. Therefore, no adjudication method as described (e.g., 2+1) was used or is applicable.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

• No, an MRMC comparative effectiveness study was not done.
• This device is an automated immunoassay for analytical detection, not a system designed to assist human readers in a diagnostic task (e.g., interpreting medical images). Therefore, a study comparing human readers with and without AI assistance is not relevant to this device.

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

• Yes, this entire submission details standalone (algorithm only) performance.
• The Amphetamines II Assay is an automated in vitro diagnostic test run on COBAS INTEGRA systems. Its performance data (precision, accuracy, specificity, interference) are all based on the analytical capabilities of the instrument and reagents without human intervention in the result determination process. Human involvement would be limited to operating the analyzer, reviewing quality control, and interpreting the final preliminary positive/negative result in a clinical context (which the device explicitly states should be followed by GC/MS confirmation and professional judgment).

7. The Type of Ground Truth Used

• The primary ground truth used for the accuracy study was Gas Chromatography/Mass Spectrometry (GC/MS) results. This is a highly accurate and specific analytical method, often considered the "gold standard" for drug confirmation in toxicology.
• For precision and some interference studies, spiked urine samples with known concentrations of d-methamphetamine or d-amphetamine were used, where the known concentration is the ground truth.

8. The Sample Size for the Training Set

• The document does not mention a training set sample size.
• This is an immunoassay, not a machine learning or AI-based diagnostic tool that typically requires a large training set. The "training" of such a system involves the development and optimization of the reagents and assay parameters by the manufacturer, rather than a data-driven training process in the sense of machine learning.

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

• As a traditional immunoassay, there is no explicit "training set" in the machine learning sense.
• The development of the assay's reagents, antibody specificity, and reaction conditions would have been guided by extensive biochemical research and experimentation to ensure specific binding and accurate signal generation across the desired concentration range. The "ground truth" during this development (or "training") phase would be the known concentrations of target analytes and interfering substances used to optimize the assay's performance characteristics. This is an iterative process of development and validation, rather than a single training set with established ground truth.

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Amphetamines II (AMPII) is an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines on automated clinical chemistry analyzers at cutoff concentrations of 300 ng/mL, 500 ng/mL and 1000 ng/mL when calibrated with d-methamphetamine. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC/MS).

Amphetamines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional iudgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

The Amphetamines II assay is based on the kinetic interaction of microparticles in a solution (KIMS) as measured by changes in light transmission. In the absence of sample drug, soluble drug-polymer conjugates bind to antibody-bound microparticles, causing the formation of particle aggregates. As the aggregation reaction proceeds in the absence of sample, the absorbance increases.

When a urine sample contains the drug in question, this drug competes with the conjugate-bound drug derivative for microparticle-bound antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited.

The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The provided text describes the 510(k) summary for the Amphetamines II Assay, Hitachi 917. However, it does not contain the specific details required to answer all parts of your request, particularly regarding detailed study results, acceptance criteria tables with performance, sample sizes for test sets with data provenance, number and qualifications of experts, adjudication methods, MRMC studies, or training set information.

The document primarily focuses on describing the device, its intended use, and its substantial equivalence to predicate devices, as required for 510(k) clearance. Clinical performance data, when present in such documents, often provides high-level summaries rather than granular details.

Here's a breakdown of what information can be extracted and what is missing:

1. Table of Acceptance Criteria and Reported Device Performance:

• Acceptance Criteria: Not explicitly stated as a table with numerical targets. The document focuses on demonstrating "substantial equivalence" to predicate devices and adherence to the intended use. The various cutoff concentrations (300, 500, 1000 ng/mL) could be considered implicit 'targets' for detection.
• Reported Device Performance: No quantitative performance metrics (e.g., sensitivity, specificity, accuracy against a gold standard) are presented in a formal table with acceptance criteria.

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

• Not provided. The document describes the assay but does not detail the clinical study design, including the number of samples used for testing, their origin, or whether they were retrospective or prospective.

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

• Not applicable/Not provided. For a drug assay like this, the "ground truth" is typically established by a reference method (e.g., GC/MS), not by human experts interpreting results. The document states: "A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method."

4. Adjudication Method for the Test Set:

• Not applicable/Not provided. As stated above, ground truth for this type of device is chemical confirmation, not human 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 device is a diagnostic assay (chemical kit) and does not involve human readers interpreting images or data alongside an AI. Therefore, an MRMC study and AI assistance improvement are not relevant concepts for this product.

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

• Yes, implicitly. The device itself is a standalone analytical test system. Its performance is evaluated on its ability to detect amphetamines and methamphetamines in urine samples. The purpose of the assay is to provide a "preliminary analytical test result," which then requires a confirmatory method like GC/MS. This means the device itself operates without human interpretation of its internal mechanics, but its results are then interpreted by laboratory personnel. However, there are no specific standalone performance metrics (like sensitivity/specificity) for the device itself against a ground truth mentioned in the provided text.

7. The Type of Ground Truth Used:

• Confirmatory chemical method, specifically Gas Chromatography/Mass Spectrometry (GC/MS). The document explicitly states: "A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method."

8. The Sample Size for the Training Set:

• Not provided. This information is typically not included in a 510(k) summary for this type of device, as "training sets" are more commonly associated with machine learning algorithms. For chemical assays, the development process involves reagent optimization and validation, rather than a distinct "training set."

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

• Not applicable. See point 8.

In summary, while the provided 510(k) summary clearly describes the device and its intended use, it lacks the detailed study performance data, sample sizes, and expert ground truth information that would be typical for an AI/software device submission. This is expected, as the Amphetamines II Assay is a chemical diagnostic kit, and its regulatory submission focuses on different aspects of validation compared to, for instance, an AI-powered image analysis system.

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The C.f.a.s. DAT Qualitative Plus Clinical calibrator is designed for the qualitative calibration of the Roche assays for drugs of abuse in human urine on automated clinical chemistry analyzers. The Control Set DAT Clinical is for use as an assayed control in the Roche test system for qualitative and semiquantitative determination of drugs of abuse in human urine on automated clinical chemistry analyzers.

C.f.a.s. DAT Qualitative Plus Clinical calibrators contain a mixture of 10 different drugs, prepared by quantitative addition of drug or drug metabolite to drug-free human urine. Drugs included are amphetamines, barbituates, benzodiazepines, cannabinoids, cocaine, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. The calibrator set contains a single level for each drug in a drug mixture. Drug concentrations are verified by gas chromatography/mass spectrometry (GC/MS). Control Set DAT Clinical controls contain a mixture of 10 different drugs, prepared by quantitative addition of drug or drug metabolite to drug-free human urine. Drugs included are amphetamines, barbituates, benzodiazepines, cannabinoids, cocaine, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. Drug concentrations are verified by gas chromatography/mass spectrometry (GC/MS). Target concentrations are established at ±25% of the assay cutoff.

The provided text is a 510(k) summary for the C.f.a.s. DAT Qualitative Plus Clinical and Control Set DAT Clinical devices. It establishes substantial equivalence to previously marketed predicate devices rather than proving a device meets specific acceptance criteria through a study with performance metrics.

Therefore, many of the requested sections (acceptance criteria table, sample sizes, expert qualifications, adjudication methods, MRMC studies, standalone performance studies, training set details) are not applicable or not provided in this type of submission.

Here's an analysis based on the information available:

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

This document describes calibrators and controls for drug-of-abuse testing, not a diagnostic device with performance metrics like sensitivity and specificity against a clinical condition. Therefore, there are no specific "acceptance criteria" for clinical performance in the sense of a diagnostic test, nor reported device performance in terms of clinical accuracy (e.g., sensitivity, specificity, accuracy).

Instead, the acceptance criteria for these calibrators and controls revolve around their composition, their traceability to GC/MS verification, and their intended use for calibrating and controlling Roche assays. The "performance" is implicitly that they function as intended for these purposes when used with the specified assays.

The table below summarizes the device characteristics rather than performance against acceptance criteria in a clinical study:

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

Not applicable. This is a 510(k) for calibrators and controls based on substantial equivalence, not a clinical study on a device's performance against a test set of patient samples. The verification of drug concentrations is done via GC/MS of the manufactured calibrator/control product itself, not on patient samples.

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)

Not applicable. Ground truth for the drug concentrations within the calibrators and controls is established by Gas Chromatography/Mass Spectrometry (GC/MS), which is an analytical method, not by human experts.

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

Not applicable, as no human adjudication of results is involved in establishing the ground truth for these calibrators and controls. The drug concentrations are verified by GC/MS.

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 not an AI-assisted diagnostic tool, and no MRMC study or AI-related performance evaluation is relevant or mentioned.

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

Not applicable. This device is a calibrator/control material, not an algorithm.

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

The ground truth for the drug concentrations within the calibrators and controls is established by Gas Chromatography/Mass Spectrometry (GC/MS). This is a highly accurate analytical technique used to verify the precise amount of each drug or drug metabolite added to the drug-free human urine matrix.

8. The sample size for the training set

Not applicable. There is no "training set" in the context of this 510(k) submission. These are manufactured chemical reference materials, not machine learning algorithms that require training data.

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

Not applicable. As there is no training set, there is no ground truth establishment for one.

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