(77 days)
The Fungitell® STAT assay is a protease zymogen-based colorimetric assay for the qualitative detection of (1->3)-B-D-glucan in the serum of patients with symptoms of, or medical conditions predisposing the patient to, invasive fungal infection. The serum concentration of (1->3)-B-glucan, a major cell-wall component of various medically important fungis, can be used as an aid in the diagnosis of deep-seated mycoses and fungemias . A positive result does not indicate which genus of fungi may be causing infection.
(1->3)-B-D-glucan index values should be used in conjunction with other diagnostic procedures, such as microbiological culture, histological examination of biopsy samples and radiological examination.
The Fungitell® STAT assay provides a qualitative measurement of (1-3)-D-Dglucan. The assay is based upon a modification of the Limulus Amebocyte Lysate (LAL) pathway. The Fungitell® STAT Reagent is modified to eliminate bacterial endotoxin reactivity and, thus, to only react to (1->3)-B-glucan, through the Factor Gmediated side of the pathway. (1->3)-3-D-glucan activates Factor G, a serine protease zymogen. The activated Factor G converts the inactive pro-clotting enzyme to the active clotting enzyme, which in turn cleaves the para-nitroanilide substrate, Boc-Leu-Gly-Arg-pNA, creating a chromophore, para-nitroaniline (pNA), that absorbs at 405 nm. The Fungitell® STAT kinetic assay is based upon the determination of the rate of optical density increase produced by a sample. This rate is interpreted against the rate of optical density increase of the Fungitell® STAT Standard to produce an index. This patient sample index value is qualitatively interpreted as a Negative, Indeterminate or Positive result according to the index value ranges provided in Table 1 below. The Fungitell® STAT Standard is calibrated at 80 +/- 8 pg/mL which is the Positive cut-off for the Fungitell® predicate.
Here's a summary of the acceptance criteria and study details for the Fungitell® STAT device, based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Acceptance Criteria (from predicate Fungitell®) | Reported Device Performance (Fungitell® STAT) |
|---|---|---|
| PPA (Positive Percent Agreement) | Not explicitly stated, inferred from predicate's established performance | 99.2% (95% CI: 95.4%, 99.9%) |
| NPA (Negative Percent Agreement) | Not explicitly stated, inferred from predicate's established performance | 97.6% (95% CI: 95.4%, 99.9%) |
| Precision/Reproducibility | Consistent with predicate Fungitell® assay | Intra-assay % CV: 0.4% to 26.8%; Inter-assay % CV: 11% to 20.44% (considered consistent) |
| Index Cut-off Values | Not explicitly stated as "acceptance criteria," but established based on predicate performance. | Negative: ≤ 0.74; Indeterminate: 0.75 - 1.1; Positive: ≥ 1.2 |
Study Details
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Sample sizes used for the test set and the data provenance:
- Assay Cut-off study: 93 de-identified patient serum samples.
- 44 Positive, 15 Indeterminate, and 34 Negative based on the predicate device Fungitell®.
- Method Comparison study: 488 de-identified patient serum samples.
- 309 Negative, 36 Indeterminate, and 143 Positive based on the predicate device Fungitell®.
- Data Provenance: De-identified patient serum samples collected for routine clinical care of the intended population. Retrospective, as these were pre-existing samples. Country of origin not specified, but the study was performed at a CLIA laboratory, suggesting a US context.
- Assay Cut-off study: 93 de-identified patient serum samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the test set (both cut-off and method comparison studies) was established by comparing to the predicate device, Fungitell®. There is no mention of human experts directly establishing ground truth for these studies.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- No adjudication method involving human readers is mentioned for the test set. All comparisons were made against the predicate device.
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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 comparative effectiveness study was performed or mentioned. This is an in vitro diagnostic device, not an AI-assisted diagnostic.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies (Assay Cut-off, Method Comparison, Precision/Reproducibility) represent standalone performance of the Fungitell® STAT device. Its measurements and interpretations are independent of human-in-the-loop analysis beyond the initial sample collection and processing.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The primary ground truth used for performance evaluation was the results from the legally marketed predicate device, Fungitell®. The (1->3)-B-D-Glucan concentrations in the samples were distributed over the full measuring range of the predicate device's standard curve.
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The sample size for the training set:
- The document does not describe a separate "training set" in the context of machine learning. The Fungitell® STAT is a modified biochemical assay, not an AI/ML algorithm requiring a distinct training phase.
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How the ground truth for the training set was established:
- As there's no mention of an ML/AI model with a training set, this question is not applicable in the context of this device's development as described. The "calibration" of the Fungitell® STAT Standard (using Saccharomyces cerevisiae) was done against the predicate assay's glucan standard, which could be considered an analogous process to establishing a baseline reference.
§ 866.3050 Beta-glucan serological assays.
(a)
Identification. Beta-glucan serological assays are devices that consist of antigens or proteases used in serological assays. The device is intended for use for the presumptive diagnosis of fungal infection. The assay is indicated for use in patients with symptoms of, or medical conditions predisposing the patient to invasive fungal infection. The device can be used as an aid in the diagnosis of deep seated mycoses and fungemias.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Serological Assays for the Detection of Beta-Glucan.” See § 866.1(e) for the availability of this guidance document.