(55 days)
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay intended for use in the quantitative analysis of caffeine levels in human serum in subjects undergoing therapy with caffeine, especially in cases of neonatal apnea.
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in biological fluids. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate deyhdrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH. resulting in an absorbance change that can be measured spectrophotometrically.
This document describes the Emit® Caffeine Assay, a homogeneous enzyme immunoassay for the quantitative analysis of caffeine levels in human serum.
Here's an analysis of the provided information regarding acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., a specific correlation coefficient or accuracy range that the device needed to meet to be deemed acceptable). Instead, it presents the results of a method comparison study as evidence of equivalence.
| Performance Metric | Reported Device Performance | Acceptance Criteria (Explicitly Stated) |
|---|---|---|
| Correlation with HPLC (Caffeine levels) | Excellent correlation with HPLC (correlation coefficient = 0.99) | Not explicitly stated |
Note: The phrase "excellent correlation" implies a qualitative acceptance, but a specific quantitative threshold for the correlation coefficient is not provided. The study's purpose was to demonstrate "substantial equivalence" to a predicate device for a broader intended use, rather than meeting novel performance criteria.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 110 neonate samples.
- Data Provenance: Retrospective, as all samples were collected from patients who had already received Theophylline or Caffeine. The country of origin is not specified but can be inferred to be the USA given the FDA submission.
- 31 samples were from patients who had received Theophylline.
- 79 samples were from patients who had received Caffeine.
- The values of these samples "spanned the assay range."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This type of information is generally not applicable to a diagnostic assay for a chemical compound like caffeine. The ground truth (reference method) was established using High-Performance Liquid Chromatography (HPLC). HPLC is a well-established analytical technique and does not require "experts" in the sense of human readers for interpretation, but rather skilled laboratory personnel to operate the equipment and interpret chromatograms.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by an objective analytical method (HPLC), not by human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is more relevant for imaging devices or other diagnostics where human interpretation plays a significant role. The Emit® Caffeine Assay is an in-vitro diagnostic (IVD) assay that produces a quantitative result, not an image or subjective interpretation.
6. Standalone Performance Study
Yes, a standalone study was implicitly performed. The method comparison study directly evaluated the Emit® Caffeine Assay's performance against HPLC without human intervention in the assay's execution or result generation. The "correlation coefficient = 0.99" refers to the algorithm's (assay's) performance.
7. Type of Ground Truth Used
The type of ground truth used was High-Performance Liquid Chromatography (HPLC). HPLC is a recognized gold standard analytical method for quantifying various substances, including caffeine, in biological samples.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its sample size. This type of terminology (training set/test set) is more commonly used in machine learning or AI-based device development. For this immunoassay, the "development" or "validation" of the assay's performance characteristics (like linearity, precision, etc.) would have been established during the initial clearance (K853872), and the current submission is focused on demonstrating equivalence for an expanded intended use. The 110 samples mentioned were used for a method comparison study, which serves as a validation (or test) of the device against a gold standard for its expanded indication rather than for training.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is mentioned in the context of this device and study, the method for establishing its ground truth is not applicable. The assay's fundamental characteristics (e.g., dose-response curve, calibration) would have been established using known concentrations of caffeine in a laboratory setting during its initial development, but this is not generally referred to as establishing "ground truth for a training set" in this context.
§ 862.3880 Theophylline test system.
(a)
Identification. A theophylline test system is a device intended to measure theophylline (a drug used for stimulation of the muscles in the cardiovascular, respiratory, and central nervous systems) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of theophylline overdose or in monitoring levels of theophylline to ensure appropriate therapy.(b)
Classification. Class II.