(354 days)
The RapidFRET Oral Fluid Assay for Cocaine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for cocaine at 20 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay is calibrated with Cocaine and provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Cocaine Calibrator Set and RapidFRET Oral Fluid Cocaine Control Set are intended for use with the RapidFRET Oral Fluid Assay for Cocaine and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Assay for Cocaine is an In Vitro Diagnostic competitive immunoassay used to detect cocaine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.
Here's a breakdown of the acceptance criteria and study information for the RapidFRET Oral Fluid Assay for Cocaine, as extracted from the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | Consistent and accurate results across multiple runs and reagent lots, especially near the cutoff concentration. | Spiked Samples (0% to 200% of cutoff, n=180 per concentration): |
- 0%, 25%, 50% of cutoff (0, 5, 10 ng/mL): 100% Negative (0% Positive)
- 75% of cutoff (15 ng/mL): 99% Negative (1% Positive)
- 100% of cutoff (20 ng/mL): 52% Negative, 48% Positive
- 125% of cutoff (25 ng/mL): 5% Negative, 95% Positive
- 150%, 175%, 200% of cutoff (30, 35, 40 ng/mL): 100% Positive (0% Negative)
Conclusion: Analytical sensitivity is between 75% and 125% of cutoff, with expected results achieved at 97% frequency within this range. |
| Accuracy / Correlation with MS Quantitation | High agreement with confirmatory methods (GC/MS or LC/MS/MS) for both positive and negative samples. | Clinical Samples (n=294): - Low Negative (30 ng/mL by MS): 0 RapidFRET NEG, 55 RapidFRET POS.
Conclusion: Accurate >99% of the time in neat oral fluid samples. |
| Cross-Reactivity & Analytical Specificity | Limited and identified cross-reactivity with structurally similar compounds, and no significant interference from common substances, foods, or dental products. | Structurally Related Compounds (171 compounds screened, 13 identified): - Benzoylecgonine: 18 ng/mL (111% cross-reactivity)
- Cocaethylene: 15 ng/mL (133% cross-reactivity)
- Cinnamoylcocaine: 224 ng/mL (8.2% cross-reactivity)
- Others: Chlorpromazine, Clomipramine, Cyclobenzaprine, Ecgonine, Ecgonine methyl ester, Imipramine, Isoxsuprine (HMMC), Norcocaine, Perphenazine, Thioridazine, Trifluoperazine showed cross-reactivity below 30,000 ng/mL (0.1% to 2.4%).
Common Substances: All tested compounds (HSA, ethanol, baking soda, blood, etc.), pH variations (5-9), and various mouth/food products (mouthwash, cough syrup, cranberry juice, etc.) showed expected NEG results with 10 ng/mL cocaine and POS results with 30 ng/mL cocaine (i.e., no significant interference at concentrations tested). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision and Analytical Sensitivity Test Set: For precision, 180 samples were tested for each concentration level (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff). This involved triplicate samples per run, 4 times daily for 5 days using 3 independent lots of reagent.
- Correlation with MS Quantitation Test Set: 294 samples were collected.
- Data Provenance:
- Precision and Analytical Sensitivity: "Negative oral fluid pools were spiked with cocaine..." This suggests a controlled laboratory setting, likely in the US where the company is based.
- Correlation with MS Quantitation: "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for opiates." This implies prospective collection from human subjects, but the country of origin is not explicitly stated. Given the submission to the FDA, it's highly probable the study was conducted in the US.
- Cross Reactivity and Analytical Specificity: Compound library testing and common substance/food testing were conducted in a laboratory setting.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Precision and Analytical Sensitivity: For this study, the ground truth was established by spiking known concentrations of cocaine into negative oral fluid. No independent experts were explicitly mentioned for determining the "ground truth" for the spiked samples, as the concentrations were precisely controlled.
- Correlation with MS Quantitation: The ground truth was established by confirmatory testing using GC/MS or LC/MS/MS. While these are highly accurate analytical methods, the text does not specify the number or qualifications of experts performing or interpreting these confirmatory tests. It's standard practice that such analyses are performed by qualified laboratory personnel.
- Cross Reactivity and Analytical Specificity: The ground truth for cross-reactivity studies was based on known concentrations of the spiked compounds and their expected interaction with the assay, verified by the assay itself relative to the cutoff. For common substances, the ground truth was the known presence/absence of cocaine spikes and the expectation of no interference from the common substance. No external experts for ground truth establishment are explicitly stated beyond the analytical methods.
4. Adjudication Method for the Test Set
The provided text does not describe an explicit adjudication method for discrepant results, such as 2+1 or 3+1. For the correlation study, samples were "sent for confirmatory testing (GC/MS or LC/MS/MS)" after initial screening. This suggests that the confirmatory method served as the de-facto gold standard to resolve any initial screening discrepancies, rather than an expert panel adjudication process from multiple readers/interpreters of the device's results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not described in this document. This device is an in-vitro diagnostic (IVD) assay where the output is a qualitative (positive/negative) result from an automated instrument, not an image or data requiring human interpretation for diagnosis in the same way an AI for medical imaging would. The "human-in-the-loop" aspect here refers to a lab technician performing the test and interpreting the instrument's output based on established cutoffs.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Device Was Done
Yes, the studies reported are standalone performance studies of the RapidFRET Oral Fluid Assay for Cocaine. The device is a "homogeneous time-resolved fluorescence assay" designed for use on an "Integrated Workstation." The performance data (precision, accuracy, cross-reactivity) refer to the analytical performance of the assay system itself, providing a qualitative (positive/negative) result directly, without requiring human interpretation of complex patterns or classifications beyond reading the instrument's output against the defined cutoff. The "human-in-the-loop" here is limited to sample collection, loading, and result reporting, rather than diagnostic interpretation.
7. The Type of Ground Truth Used
- Precision and Analytical Sensitivity: Spiked known concentrations of cocaine.
- Correlation with MS Quantitation: Confirmatory analytical methods (GC/MS or LC/MS/MS).
- Cross Reactivity and Analytical Specificity: Known concentrations of spiked compounds and their expected behavior (presence/absence of cocaine for the interference studies).
8. The Sample Size for the Training Set
The document does not explicitly state the sample size for a "training set." This is common for this type of IVD device where development often involves iterative optimization and validation across various sample types and spike levels, rather than a distinct "training set" and "test set" in the context of machine learning. The studies described are more akin to validation studies demonstrating the device's performance characteristics.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" is not detailed, the method for establishing ground truth for training is not provided. However, generally, for the development of such assays, manufacturers would leverage:
- Well-characterized samples: Including known positive and negative samples, and samples spiked with varying concentrations of the analyte and potential interferents.
- Reference methods: Using established gold-standard analytical techniques (like GC/MS or LC/MS/MS) to confirm analyte concentrations in samples used for assay development and optimization.
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).