(214 days)
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."
| Category | Acceptance Criteria (Implied / Desired) | Reported Device Performance (from Comparison Study with GC/MS) |
|---|---|---|
| Precision | Consistent results at various concentrations relative to the cutoff (3 ng phencyclidine/10 mg hair) | Intra-Assay Precision: |
- 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
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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.
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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.
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Sample Shipping Stability:
- 7 phencyclidine positive samples.
- Data Provenance: Not explicitly stated, but implies real or spiked positive samples tested after storage and shipping.
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Cosmetic Treatments:
- 5 phencyclidine-negative head hair samples.
- 10 phencyclidine-positive head hair samples.
- Data Provenance: In-house laboratory study.
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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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