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

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

The test consists of two parts; a pre-analytical hair treatment procedure (to extract phencyclidine from the solid hair matrix to a measurable liquid matrix) and the screening assay, the Psychemedics Phencyclidine Homogeneous Enzyme Immunoassay. The screening portion of the test system is based on competition for antibody binding sites between drug in the measurable liquid matrix and drug-labeled recombinant glucose-6-phosphate dehydrogenase (G6PDH). As the antibody binds labeled G6PDH, enzyme activity decreases. In the presence of drug, enzyme activity increases in direct proportion to the drug concentration. Active enzyme reduces nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically The Psychemedics Phencyclidine HEIA consists of reagents R1 (anti-phencyclidine monoclonal antibody with substrate) and R2 (phencyclidine labeled recombinant G6PDH).

Here's an analysis of the provided text, focusing on the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" with defined numerical targets for sensitivity, specificity, or accuracy. Instead, the performance is described through precision studies and comparison studies using a specific cut-off. For the purpose of this analysis, the reported performance from the comparison study with GC/MS (the preferred confirmatory method) will be presented as the de facto "reported device performance."

• At -100%, -75%, -50%, -25% of cutoff: 8 negative results, 0 positive results.
• At +25%, +50%, +75%, +100% of cutoff: 0 negative results, 8 positive results.
  Inter-Assay Precision:
• At -100%, -75%, -50%, -25% of cutoff: 80 negative results, 0 positive results.
• At +25%, +50%, +75%, +100% of cutoff: 0 negative results, 80 positive results. |
  | Cross-Reactivity | Minimal or no interference from common substances and compounds, except for expected cross-reactants. Expected cross-reactants should have a known equivalent concentration to the 3.0 ng phencyclidine/10 mg hair cutoff. | Cross-Reactive Compounds (≥ 3 ng Phencyclidine/10 mg hair equivalent):
• Venlafaxine: 100% cross-reactivity (3 ng equivalent)
• Rolicyclidine HCl: 37.5% (8 ng equivalent)
• 3-Methoxy-(Aryl Ring) PCP: 30% (10 ng equivalent)
• 4-Hydroxy (Cyclohexyl Ring) PCP: 12% (25 ng equivalent)
• 1-(1-Phenylcyclohexyl)-4-hydroxypiperidine: 6% (50 ng equivalent)
• 1-(1-Phenylcyclohexyl) Morpholine (PCM): 6% (50 ng equivalent)
• Metaphit: 4% (75 ng equivalent)
• Atropine: 3% (100 ng equivalent)
  No Cross-Reactivity: A long list of compounds including Anhydroecgonine Methyl Ester, Bupropion, Cotinine, Cannabinol, etc., showed no cross-reactivity. |
  | Interference | Minimal or no interference from substances that affect the assay at relevant concentrations. | Interfering Compounds (at 100 ng interferent per 10 mg hair):
• Atropine
• Chlorpheniramine Maleate
• Venlafaxine
  No Interference: A long list of compounds including Anhydroecgonine Methyl Ester, Bupropion, Cotinine, Cannabinol, etc., showed no interference. |
  | Sample Shipping Stability | Phencyclidine remains detectable and stable in hair samples after storage and shipping. | 7 phencyclidine positive samples remained positive after approximately 8 months in storage and after shipping twice coast-to-coast. |
  | Recovery | Extraction method should efficiently recover phencyclidine from hair matrix. | Average recovery was approximately 86% complete after extraction for 3 hours. |
  | Cosmetic Treatments | Cosmetic treatments (perm, dye, shampoo, relaxer) should not cause false positives in negative samples, nor false negatives in positive samples. | Negative Samples: 5 phencyclidine-negative head hair samples remained negative after treatment with perm, dye, shampoo, and relaxer.
  Positive Samples: 10 phencyclidine-positive head hair samples remained positive after treatment with perm, dye, shampoo, and relaxer. |
  | Overall Agreement with GC/MS | High concordance between the immunoassay (HEIA) and the confirmatory method (GC/MS) especially for samples around and above the cutoff, recognizing potential discrepancies due to washing procedures for confirmation. | Unwashed GC/MS Comparison:
• HEIA Positive / GC/MS 4.5 ng: 40
• HEIA Negative / GC/MS 4.5 ng: 0
  Washed GC/MS Comparison:
• HEIA Positive / GC/MS 4.5 ng: 35
• HEIA Negative / GC/MS 4.5 ng: 0
  Discordant Results (Positive HEIA/Negative GC/MS after washing): Two samples were positive by HEIA but below cutoff (2.47 and 1.73 ng/10 mg hair) after extended washing for GC/MS. This is attributed to the removal of sweat-derived drug and/or environmental contamination by washing, which is not performed prior to screening. |

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

• Precision Studies:

  • Intra-Assay Precision: 8 replicates per concentration level (negative, cutoff, +/- 25%, 50%, 75%, 100% of cutoff).
  • Inter-Assay Precision: 80 replicates per concentration level (negative, cutoff, +/- 25%, 50%, 75%, 100% of cutoff).
  • Data Provenance: Spiked negative hair with GC/MS validated calibrator and control solutions. The origin of the "negative hair" is not specified but would likely come from in-house or commercial sources. This is a laboratory-controlled study.

• Cross-Reactivity and Interference Studies:

  • The number of samples/tests for each compound is not explicitly stated but implies testing each compound at various concentrations or single key concentrations.
  • Data Provenance: Laboratory-controlled studies using the listed compounds.

• Sample Shipping Stability:

  • 7 phencyclidine positive samples.
  • Data Provenance: Not explicitly stated, but implies real or spiked positive samples tested after storage and shipping.

• Cosmetic Treatments:

  • 5 phencyclidine-negative head hair samples.
  • 10 phencyclidine-positive head hair samples.
  • Data Provenance: In-house laboratory study.

• Comparison Studies (Primary Test Set):

  • Total N = 84 individual hair samples.
  • 40 negative samples (by predicate device and HEIA).
  • 44 positive samples (by predicate device and HEIA).
  • Data Provenance: Collected anonymously from a workplace setting. This indicates retrospective real-world samples. The country of origin is not explicitly stated but assumed to be the U.S. given the FDA submission.

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

The ground truth for the comparison study was established by Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is described as the "preferred confirmatory method."

• The document implies that the GC/MS analysis itself establishes the ground truth, rather than human experts interpreting the GC/MS results.
• Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth in the traditional sense of image or clinical interpretation is not directly applicable here. The GC/MS instrument and its operating/interpreting technicians (who are typically highly qualified analytical chemists or toxicologists) serve to establish the "ground truth" through a validated analytical method.

4. Adjudication Method for the Test Set

• The adjudication method is a direct comparison between the investigational device (Psychemedics HEIA) and the GC/MS confirmatory assay.
• Initially, samples were identified as positive or negative using the predicate device (Psychemedics phencyclidine microplate assay, K111928) and then tested with the HEIA device. The HEIA results were then compared to the GC/MS confirmatory assay.
• For discordant results (e.g., HEIA positive, GC/MS negative after washing), explanations are provided regarding the effect of washing on GC/MS results. This suggests that GC/MS is the ultimate arbiter, even with these nuances. There is no mention of a human consensus or additional adjudicator comparing the HEIA and GC/MS results and making a final decision beyond what the GC/MS represents as the "confirmed analytical result."

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, If So, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

• No, an MRMC comparative effectiveness study was not done.
• This device is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that requires human interpretation based on images or complex clinical data. Therefore, the concept of "human readers improve with AI vs 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, the primary performance evaluation is a standalone performance study.
• The Psychemedics HEIA for Phencyclidine in Hair is an automated enzyme immunoassay system. Its performance is evaluated directly against the GC/MS confirmatory method without human interpretation as part of the assay itself. The results (positive/negative) are generated directly by the assay and optical reader.

7. The Type of Ground Truth Used

• The primary ground truth used is Gas Chromatography/Mass Spectrometry (GC/MS) confirmation. This is a highly specific and sensitive analytical method for drug detection and quantification, considered the "gold standard" for confirmation in forensic toxicology.
• The document refers to it as the "preferred confirmatory method" and states that "a more specific alternative chemical method must be used in order to obtain a confirmed analytical result" after the preliminary immunoassay.

8. The Sample Size for the Training Set

• The document does not explicitly state a sample size for a "training set."
• Immunoassays are typically developed and optimized through iterative processes based on analytical chemistry principles and validation against known standards, rather than machine learning training sets in the computational sense.
• The calibrators and control materials used for assay setup and validation are prepared from "drug stocks purchased from a commercial vendor," implying a controlled manufacturing and quality assurance process, not a data-driven training set.

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

• As there is no distinct "training set" in the machine learning sense, the concept of establishing ground truth for it is not applicable.
• However, the underlying data for the calibrators and controls used in assay development and daily operation have their concentrations "confirmed by GC/MS." This ensures the accuracy of the reference materials against which the immunoassay is designed to perform.

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

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

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

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

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

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

1. Table of Acceptance Criteria and Reported Device Performance

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

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

Inferred Acceptance Criteria vs. Reported Performance:

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

2. Sample Sizes and Data Provenance for the Test Set

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

• Precision Studies:

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

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

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

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

• Cosmetic Treatment Studies:

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

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

• Recovery: Not specified, likely laboratory experiments.

3. Number of Experts and Qualifications for Ground Truth

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

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

4. Adjudication Method for the Test Set

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

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

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

6. Standalone (Algorithm Only) Performance

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

7. Type of Ground Truth Used

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

8. Sample Size for the Training Set

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

9. How Ground Truth for the Training Set Was Established

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

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The Psychemedics homogeneous enzyme immunoassay (HEIA) for opiates in hair is an enzyme immunoassay for the preliminary qualitative detection of opiates in human head and body hair using a morphine calibrator at 2 ng morphine/10 mg hair for the purpose of identifying opiate use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for opiates in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/ MS/MS) is the preferred confirmatory method.

The Psychemedics homogeneous enzyme immunoassay (HEIA) for oxycodone in hair is an enzyme immunoassay for the preliminary qualitative detection of oxycodone in human head and body hair using an oxycodone calibrator at 2 ng oxycodone/10 mg hair for the purpose of identifying opioid use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone. The Psychemedics homogeneous enzyme immunoassay for oxycodone in hair provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) is the preferred confirmatory method.

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

The Psychemedics Opiates HEIA consists of reagents R1 (anti-opiates monoclonal antibody with substrate) and R2 (morphine labeled recombinant G6PDH). The Psychemedics Oxycodone HEIA consists of reagents R1 (anti-oxycodone monoclonal antibody with substrate) and R2 (oxycodone labeled recombinant G6PDH).

Below you will find the acceptance criteria and study details for the Psychemedics Homogeneous Enzyme Immunoassay (HEIA) for Opiates and Oxycodone in Hair:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly demonstrated by the performance studies showing the device's ability to accurately classify samples as positive or negative compared to LC/MS/MS confirmation, especially at and around the cut-off concentrations. The stated goal for both assays is to provide a "preliminary qualitative detection" of opiates or oxycodone.

The performance is reported in terms of precision (intra-assay and inter-assay), cross-reactivity, and comparison studies against LC/MS/MS.

General Acceptance Criteria (Implied by the study results presented):

• Precision: The assay should reliably produce consistent results for samples at various concentrations around the cutoff, indicating good repeatability and reproducibility. The reported data shows 100% agreement (either all negative or all positive) for samples at different concentrations relative to the cutoff for both intra-assay and inter-assay precision.
• Specificity (Cross-reactivity): The assay should primarily detect the target analytes (opiates or oxycodone) and have minimal cross-reactivity with other structurally similar compounds or common substances. The cross-reactivity tables indicate which compounds show cross-reactivity and at what concentrations. Compounds showing no cross-reactivity are also listed.
• Interference: The assay should not be significantly impacted by common interfering substances, including cosmetic treatments. The study reports no interference from numerous compounds, and also notes which compounds show interference (e.g., imipramine in the oxycodone assay). Cosmetic treatments also did not alter the results for both positive and negative samples.
• Agreement with Confirmatory Method (LC/MS/MS): The preliminary qualitative results should show reasonable agreement with the definitive LC/MS/MS confirmatory method, especially highlighting how the assay performs around the critical cutoff concentration.

Since this is an in vitro diagnostic device for preliminary qualitative detection, the performance metrics (precision, cross-reactivity, and reasonable agreement with a confirmatory method) are the key indicators of acceptance. The device is not intended to be a standalone definitive diagnostic.

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Psychemedics Opiates HEIA: 230 individual hair samples.
   • Psychemedics Oxycodone HEIA: 219 individual hair samples.
   • Data Provenance: Samples were "collected anonymously from a workplace setting." The document does not specify the country of origin, but given the FDA submission, it's likely primarily U.S. based. The data appears retrospective, as stated "The stored hair samples were then tested..."
   • Precision Studies: Intra-assay precision involved 8 measurements per concentration level, and inter-assay precision involved 80 measurements per concentration level. These were achieved by spiking negative hair with validated calibrator and control solutions.

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

   • No human experts were used for establishing ground truth. The devices being reviewed are in vitro diagnostic devices, which perform quantitative/qualitative analysis.
   • The ground truth was established by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS), which is described as the "preferred confirmatory method" and is a highly sensitive and specific analytical technique for drug detection. This is a chemical/analytical ground truth, not an expert-driven one.

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

   • No human adjudication method was used. The comparison was directly between the test device's preliminary result and the LC/MS/MS confirmatory result.

4. 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 MRMC or human-in-the-loop study was performed. This is an immunoassay, not an AI-assisted diagnostic. Its purpose is to provide a screening result, not to assist human interpretation of complex medical images or data.

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

   • Yes, the performance studies described are standalone performance evaluations of the immunoassay itself. The device is an automated chemical analyzer.

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

   • The type of ground truth used was analytical confirmation by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS). For in vitro diagnostic assays measuring chemical substances, this is the gold standard for ground truth.

7. The sample size for the training set:

   • This document describes a 510(k) submission, which typically focuses on demonstrating substantial equivalence through performance testing, not on developing a machine learning model. Therefore, a separate "training set" in the context of AI/ML is not applicable here. The samples used for performance evaluation (230 for Opiates HEIA, 219 for Oxycodone HEIA) are test samples for validation, not a training set. The calibrators and control solutions used in precision studies would be analogous to internal "training" or calibration materials for the assay's function, but not in the sense of a dataset for model training.

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

   • As noted above, there isn't a "training set" in the AI/ML context. For the assay's internal calibration and control (which could be considered analogous), the document states: "Psychemedics prepares calibrators and control materials using drug stocks purchased from a commercial vendor. Each lot of drug is received with its specific certificate of analysis. The commercially obtained stock is made into calibrators and controls to the desired concentrations. The concentrations are confirmed by LC/MS/MS." This indicates that the ground truth for the calibrators and controls is also established by LC/MS/MS.

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The Psychemedics homogeneous enzyme immunoassay for cocaine in hair is an enzyme immunoassay for the preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair for the purpose of identifying cocaine use. This product is intended exclusively for in-house professional use and not for sale to anyone.

The Psychemedics EIA Cocaine Assay provides only a preliminary analytical test results, a more specific alternate chemical method (e.g. LC/MS/MS) must be used. Clinical consideration and professional judgement should be applied to the interpretation of any drug-of-abuse test result.

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

The Psychemedics Cocaine HEIA consists of reagents R1 (anti-cocaine monoclonal antibody with substrate) and R2 (cocaine labeled recombinant G6PDH).

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

Device Name: Psychemedics Homogeneous Enzyme Immunoassay for Cocaine in Hair

Indications for Use: Preliminary qualitative detection of cocaine in human head and body hair using a cocaine calibrator of 5 ng/10 mg hair, for identifying cocaine use. Intended for in-house professional use only. Positive results require confirmation with a more specific alternate chemical method (e.g., LC/MS/MS).

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" with specific pass/fail metrics in a table format. Instead, it details various performance studies and their results to demonstrate substantial equivalence to a predicate device. I've extracted the relevant performance metrics and will organize them as an "acceptance criteria" table for clarity, inferring the implied acceptance for each from the reported results ("all good", "no cross-reactivity", "remained positive/negative").

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The Psychemedics Microplate EIA For Cotinine in Hair is an in vitro diagnostic device for the qualitative detection of cotinine in human head and body hair as an aid in the detection of cotinine after use or exposure to tobacco products. The assay is intended for a single site and uses a cutoff calibrator of 200 pg cotinine/mg hair. This device is intended exclusively for Psychemedics use only and is not intended for sale to anyone.

The Psychemedics Microplate EIA For Cotinine in Hair provides only a preliminary analytical test result. A more specific alternate chemical method must be used to obtain a confirmed analytical result. Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS) is the confirmatory method used by Psychemedics Corporation. The LC/ MS/MS analysis uses a cutoff, after extensive washing of 100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair.

The Psychemedics Microplate EIA For Cotinine in Hair consists of two parts; a pre-analytical hair treatment procedure (to convert the solid matrix of hair to a measurable liquid matrix) and the screening assay, the Psychemedics Microplate EIA for Cotinine. The screening portion of the test system consists of (1) microplate wells coated with cotinine conjugated to bovine serum albumin (BSA), polyclonal rabbit anti-cotinine, goat antirabbit secondary antibody conjugated to HRP (horseradish peroxidase), substrate [3, 3', 5, 5' tetramethylbenzidine (TMB)], HCl to acidify (and stop the reaction), and wash buffer for washing the plates. Absorbance in the wells is read with a microplate reader.

Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS) is the confirmatory method used by Psychemedics Corporation. The LC/MS/MS analysis uses a cutoff, after extensive washing of the hair, of 100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair.

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

Acceptance Criteria and Device Performance for Psychemedics Microplate EIA for Cotinine in Hair (K192517)

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on demonstrating substantial equivalence to a predicate device and provides performance data rather than explicitly stating pre-defined "acceptance criteria" as pass/fail thresholds for specific metrics. However, based on the performance testing results, we can infer the implied acceptance criteria.

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

• Comparison Study (EIA vs. LC/MS/MS): A total of 82 samples were utilized.
  • Data Provenance: The document states "Samples were identified for inclusion in the study by screening with a screening assay for cotinine in serum (K974234)." It doesn't explicitly state the country of origin or if they were retrospectively or prospectively collected human hair samples, but implies they are human hair samples.
• Precision Studies (EIA): Not explicitly stated as "test set," but 10 samples were used for intra-assay and 50 samples for inter-assay precision at various levels around the cutoff. These were "negative hair spiked with previously LC/MS/MS-validated calibrator and control spiking solutions."
• Cosmetic Treatments: Sets of 5 cotinine-negative and 6 cotinine-positive samples (total of 11) were used.
• Environmental Contamination: 7 hair samples were exposed to smoke for this specific test.
• LC/MS/MS Recovery from Hair: 5 authentic samples.
• LC/MS/MS Precision, Linearity, LLOQ/LOD: These studies involved spiked samples rather than a separate "test set" of authentic patient samples, with varying numbers of replicates (e.g., 5 analyses, 5 samples for 5 days).
• Sample Stability during Shipping and Storage: 6 samples for shipping stability and another 6 samples for storage stability.

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

The primary "ground truth" for the comparison study and for confirming the EIA results is the Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) method. This is a laboratory-based analytical method, not directly dependent on expert human interpretation of images or clinical signs. The document does not mention human experts establishing ground truth for the test set.

4. Adjudication Method for the Test Set:

Not applicable, as the ground truth is established by the LC/MS/MS analytical method, which is a quantitative measurement, not subject to human adjudication in the traditional sense of multiple readers interpreting a case. The LC/MS/MS confirms positive cotinine levels above a certain cutoff (100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair).

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

No, an MRMC comparative effectiveness study was not done. The device is an in vitro diagnostic assay, not an imaging device or AI algorithm requiring human interpretation. The comparison is between the new EIA screening method and the confirmatory LC/MS/MS method.

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

Yes, a standalone study of the device (Psychemedics Microplate EIA for Cotinine in Hair) was performed in comparison to the LC/MS/MS confirmatory method, which serves as the "gold standard" ground truth. The EIA itself operates independently without direct human intervention in the interpretation of its results (beyond reading the microplate reader output). The final confirmed analytical result is obtained by LC/MS/MS.

7. The Type of Ground Truth Used:

The ground truth used is an alternative chemical method, specifically Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS), which is considered a highly specific and sensitive analytical technique for cotinine detection. This is a form of laboratory/analytical ground truth. The LC/MS/MS analysis uses a cutoff of 100 pg cotinine/mg hair (after extensive washing) with the presence of hydroxycotinine at or above 10 pg/mg hair.

8. The Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning. The device is a traditional enzyme immunoassay (EIA). The performance studies involve validation of the assay's characteristics (precision, linearity, cross-reactivity, etc.) using spiked samples, negative controls, and a limited number of authentic samples for comparison studies. There isn't a "training set" in the sense of data used to train an AI model.

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

Not applicable, as there is no specific "training set" for an AI model. The calibrators and control materials for the EIA and LC/MS/MS are prepared using drug stocks from commercial vendors with certificates of analysis, and their concentrations are confirmed by LC/MS/MS.

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The Psychemedics Microplate EIA For Fentanyl in Hair is an in vitro diagnostic device for the qualitative detection of fentanyl in hair. The assay is intended for use in workplace settings for the qualitative analysis of human head and body hair. The assay uses a cutoff calibrator of 0.2 ng fentanyl/10 mg hair.

Psychemedics plans to perform this test at one site. Psychemedics has not performed an evaluation of reproducibility at different laboratories.

The Psychemedics Microplate EIA For Fentanyl in Hair provides only a preliminary analytical test result. A more specific alternate chemical method must be used to obtain a confirmed analytical result. Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS) using deuterated internal standards in multiple reaction monitoring (MRM) mode is the confirmatory method used by Psychemedics Corporation. This confirmatory method uses a cutoff of 0.2 ng of fentanyl/10 mg hair.

The Psychemedics Microplate EIA For Fentanyl in Hair consists of two parts; a pre-analytical hair treatment procedure (to convert the solid matrix of hair to a measurable liquid matrix) and the screening assay, the Psychemedics Microplate EIA for Fentanyl. The screening portion of the test system consists of (1) microplate wells coated with fentanyl conjugated to bovine serum albumin (BSA), monoclonal rabbit anti-fentanyl, goat anti-rabbit secondary antibody conjugated to HRP (horseradish peroxidase), substrate [3, 3', 5, 5' tetramethylbenzidine (TMB)], HCl to acidify (and stop the reaction), and wash buffer for washing the plates. Absorbance in the wells is read with a microplate reader.

Here's a breakdown of the acceptance criteria and the supporting study for the Psychemedics Microplate EIA for Fentanyl in Hair device:

Acceptance Criteria and Reported Device Performance

• B₀ (-100%): 10 negative, 0 positive
• -75%: 10 negative, 0 positive
• -50%: 10 negative, 0 positive
• -25%: 10 negative, 0 positive
• Plus 25%: 0 negative, 10 positive
• Plus 50%: 0 negative, 10 positive
• Plus 75%: 0 negative, 10 positive
• Plus 100%: 0 negative, 10 positive

Inter-Assay Precision:

• B₀ (-100%): 50 negative, 0 positive
• -75%: 50 negative, 0 positive
• -50%: 50 negative, 0 positive
• -25%: 50 negative, 0 positive
• Plus 25%: 0 negative, 50 positive
• Plus 50%: 0 negative, 50 positive
• Plus 75%: 0 negative, 50 positive
• Plus 100%: 0 negative, 50 positive |
  | Comparison Testing | No False Negatives relative to LC/MS/MS | No false negative EIA results occurred relative to LC/MS/MS. |
  | | Limited False Positives relative to LC/MS/MS at cutoff. | Ten positive EIA results did not confirm at or above the 0.2 ng fentanyl/10 mg hair cutoff by LC/MS/MS due to washing effects or cross-reactivity with other fentanyl compounds. |
  | Cross-Reactivity | Expected cross-reactivity for related compounds, no cross-reactivity for unrelated compounds. | - Fentanyl and several analogs (Butyryl, Valeryl, Furanyl, Acetyl, o-Fluorofentanyl, Acryl, Cyclopropyl, Isobutyryl, Ocfentanil, 4-Fluoro-isobutyryl) showed high cross-reactivity (100% to 200%).
• Other related compounds show lower cross-reactivity (e.g., (+/-)-cis-3-methylfentanyl at 9.1%, Methyl fentanyl at 2%).
• Many unrelated compounds (e.g., stimulants, opiates, benzodiazepines, cannabinoids, etc.) showed no cross-reactivity. |
  | Interference | No significant interference from commonly found substances. | A wide range of specified compounds (e.g., amoxicillin, caffeine, ibuprofen, naproxen, various illicit drugs like cocaine, heroin metabolites) and mixes showed no interference in the Fentanyl EIA assay. |
  | Cosmetic Treatments | EIA results for negative and positive samples are unaffected by cosmetic treatments (bleach, perm, dye, relaxer, shampoo). | - Negative hair samples remained negative after bleach, permanent wave, dye, relaxer, and shampoo treatments.
• For positive samples, fentanyl concentration change ranged from 98.4% (shampoo) to 106.5% (relaxer) of untreated samples for dye, relaxer, shampoo, and perm, indicating no significant loss or false positivity. |
  | Environmental Contamination | Environmental contamination does not lead to false positives above cutoff after washing procedure. | After an extensive washing procedure, samples contaminated with 2 ng fentanyl/mL of saline resulted in concentrations from below LOQ to 0.0527 ng/10 mg hair, which is well below the 0.2 ng/10 mg hair cutoff. |
  | Sample Stability | Fentanyl in hair samples remains stable during shipping and storage. | Five samples showed no significant differences between results before and after shipping and one month of storage. |
  | Recovery (EIA) | Sufficient recovery of fentanyl after hair digestion. | Recovery of fentanyl in the digestion method was shown to be at least 80% complete at 2 hours. |
  | Recovery (LC/MS/MS) | High recovery of fentanyl and norfentanyl from hair. | Recovery of fentanyl and norfentanyl from 5 authentic samples was greater than 96%. Recoveries of analytes and internal standards with SPE were greater than 50% with 0.995. Actual data points deviated 90% of target and

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The Psychemedics Microplate EIA For Benzodiazepines in Hair is an in vitro diagnostic device for the qualitative detection of benzodiazepines in hair. The assay is intended for use in workplace settings for the qualitative analysis of human head and body hair. The assay uses a cutoff calibrator of 1 ng oxazepam/10 mg hair.

The immunoassay consists of two parts; a pre-analytical hair treatment procedure (to convert the solid matrix of hair to a measurable liquid matrix) and the screening assay, the Psychemedics Microplate EIA for Benzodiazepines. The screening portion of the test system consists of microplate wells coated with Oxazepam conjugated to bovine serum albumin (BSA), the prepared hair sample, a cutoff calibrator added to the sample at a concentration of 1 ng Oxazepam/10 mg hair, monoclonal mouse anti-Oxazepam antibody, goat anti-mouse secondary antibody conjugated to HRP (horseradish peroxidase), substrate [3, 3', 5, 5' tetramethylbenzidine (TMB)], HCl to acidify (and stop the reaction), and wash buffer for washing the plates. Absorbance in the wells is read with a microplate reader.

The confirmation assay consists of a AB Sciex API 3200 LC/MS/MS (Serial numbers AA24661109 and AA28841310) linked to two Shimazu LC-20AD Micro pumps and a Leap Technologies PAL autosampler.

The provided text describes the performance characteristics of the "Psychemedics Microplate EIA for Benzodiazepines in Hair" (the "device") and its supporting studies. The information is presented in the context of a 510(k) premarket notification to the FDA, demonstrating substantial equivalence to a predicate device.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for each performance metric in a pass/fail format. Instead, it describes validated ranges and outcomes that were considered acceptable for demonstrating the device's performance. The reported performance is directly from the tables and text provided.

• Negative, 25%, 50%, 75% of cutoff: 15/0 (Negative/Positive)
• Cutoff: 7/8 (Negative/Positive)
• 125%, 150%, 175%, 200% of cutoff: 0/15 (Negative/Positive)
  Inter-Assay:
• Negative, 25%, 50%, 75% of cutoff: 75/0 (Negative/Positive)
• Cutoff: 43/32 (Negative/Positive)
• 125%, 150%, 175%, 200% of cutoff: 0/75 (Negative/Positive) |
  | LC-MS/MS Precision | %CV of 10% or less for each level tested; concentrations within ± 15% of target; correlation coefficient >0.995; mean of replicates within ± 15% of predicted. | Alprazolam: %CV range 2.96% - 11.45% (n=5 samples, triplicate reps)
  Lorazepam: %CV range 4.83% - 7.42% (n=4 samples, triplicate reps)
  Diazepam: %CV range 0.91% - 12.77% (n=5 samples, triplicate reps)
  Nordiazepam: %CV range 3.81% - 7.75% (n=4 samples, triplicate reps)
  Oxazepam: %CV range 2.25% - 10.82% (n=4 samples, triplicate reps)
  Temazepam: %CV range 1.99% - 13.12% (n=5 samples, triplicate reps) |
  | LC-MS/MS Linearity | %CV ≤ 10%, concentrations within ± 15% of target, correlation coefficient >0.995, mean of replicates within ± 15% of predicted value based on linear regression. | All conditions met, establishing a linear range of 0.05 to 20.0 ng/10 mg hair for Alprazolam, Lorazepam, Diazepam, Nordiazepam, and Temazepam. |
  | LC-MS/MS Detection Limit (LLOQ) | Analyte response at LLOQ ≥ 5 times blank response; identifiable, discrete, reproducible peak; precision (CV) ≤ 20%; accuracy within 20% of nominal. | LLOQ of 0.05 ng/10 mg hair for all six benzodiazepines, with all acceptance criteria satisfied. |
  | Immunoassay Specificity (Cross-reactivity) | N/A (listed cross-reactivity percentages) | Varies significantly by compound (e.g., Clobazam 550%, Oxazepam 100%, Lorazepam 13%, 7-aminoclonazepam

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