FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The Platelia® Aspergillus EIA is a test which, when used in conjunction with other diagnostic procedures such as microbiological culture, histological examination of biopsy samples and radiographic evidence, can be used as an aid in the diagnosis of invasive aspergillosis.

Device Description

The Platelia Aspergillus EIA is a one-stage immunoenzymatic sandwich microplate assay which detects galactomannan in human serum. The assay uses the rat monoclonal antibody EBA-2, which is directed antibody is used: to coat the wells of the microplate and bind the antigen, and as the detector antibody in the conjugate reagent (peroxidase-linked monoclonal antibody).

Serum samples are heat-treated in the presence of EDTA in order to dissociate immune-complexes and to precipitate serum proteins that could possibly interfere with the test. The treated serum samples and conjugate are added to the wells coated with monoclonal antibody, and incubated. A monoclonal antibody - galactomannan - monoclonal antibody / peroxidase complex is formed in the presence of Aspergillus antigen. The strips are washed to remove any unbound material. Next, the substrate solution is added, which will react with the complexes bound to the well to form a blue color reaction. The enzyme reaction is stopped by the addition of acid, which changes the blue color to yellow. The optical absorbance of specimens and controls is determined with a spectrophotometer set at 450 and 620/630 nm wavelength.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Bio-Rad Platelia® Aspergillus EIA, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in terms of specific performance thresholds for sensitivity and specificity. Instead, these values are presented as the results of the clinical study. The reproducibility study, however, shows internal targets for coefficient of variation (%CV).

Metric	Acceptance Criteria (Implicit)	Reported Device Performance (Combined Sites)
Reproducibility	Low intra- and inter-assay variability (demonstrated by %CV)	%CVs range from 2.4% to 29.2% (depending on panel member and site)
Cross-Reactivity	No cross-reactivity with tested interfering conditions	0 positives in all 151 tested sera from various pathologies
Sensitivity	Not explicitly stated as a target	80.7% (Combined Proven and Probable Aspergillosis)
Specificity	Not explicitly stated as a target	89.2% (Combined sites, 148 control patients)
Positive Predictive Value (PPV)	Not explicitly stated as a target, dependent on prevalence	54.8% (at 14% prevalence) (68.3% after repeat testing)
Negative Predictive Value (NPV)	Not explicitly stated as a target, dependent on prevalence	96.6% (at 14% prevalence) (95.5% after repeat testing)

Study Details

Sample sizes used for the test set and the data provenance:
- Clinical Testing (Test Set):
  - Total Patients: 179
  - Total Serum Samples: 1890
  - Proven/Probable Invasive Aspergillosis Patients: 31 (528 serum samples)
  - Control Patients (without IA): 148 (1362 serum samples)
  - Data Provenance: Retrospective, collected from three sites in the U.S. and Canada.
- Reproducibility Study:
  - Panel Samples: 6 pooled patient serum samples (1 negative, 1 low positive, 2 positive, 2 high positive).
  - Replicates: 9 replicates per panel member at two sites, 6 replicates per panel member at a third site.
- Cross-Reactivity Study:
  - Sera Tested: 151 sera from patients with various medical conditions.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not specify the exact number or qualifications of experts who established the ground truth. However, it explicitly states that the diagnostic criteria for Invasive Aspergillosis (IA) were based on the Invasive Fungal Infection Cooperative Group (IFICG) of the European Organization for Research (EORTC) and the Mycosis Study Group (MSG of the National Institute of Allergy and Infectious Diseases (NIAID) definitions. These are established, expert-driven criteria in the field.
Adjudication method for the test set:
The document does not detail a specific adjudication method (e.g., 2+1, 3+1). The use of established IFICG/EORTC/NIAID definitions for "Proven" and "Probable" Invasive Aspergillosis implies a standardized diagnostic approach, which would inherently involve clinical judgment often involving multiple medical specialists (e.g., infectious disease specialists, pathologists, radiologists), but the process of arriving at these "ground truth" diagnoses for the study is not explicitly described as having a specific adjudication model.
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. This study describes the performance of an immunoassay (Platelia Aspergillus EIA) for antigen detection, not an AI software or a device requiring human interpretation for image analysis or similar tasks. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, this was a standalone performance study. The Platelia® Aspergillus EIA is an automated immunoassay that provides a quantitative index value. The reported sensitivity and specificity values are based solely on the output of this assay compared to the established ground truth, without human interpretation of the assay results impacting the "device performance" metrics themselves. Human interpretation would come into play when using the device in conjunction with other diagnostic procedures as per its intended use, but the reported performance here is of the assay itself.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth for the clinical study was established using standardized definitions for Invasive Aspergillosis:
- Proven Invasive Aspergillosis: Defined by positive microbiological culture obtained by sterile procedure from the affected site, AND histopathological demonstration of appropriate morphological forms in a host with symptoms.
- Probable Invasive Aspergillosis: Defined as at least one microbiological criterion, and one major or two minor clinical criteria from a site consistent with infection, in a host with symptoms.
- Control Patients: Patients without signs of Invasive Aspergillosis.
The sample size for the training set:
The document does not explicitly describe a separate "training set" for the device, as it is an immunoassay kit rather than a machine learning algorithm. The performance evaluation focuses on a "test set" to assess its diagnostic accuracy. The development of the assay itself (e.g., antibody selection, assay parameters) would involve internal validation and optimization, but this is distinct from the concept of a training set for an AI/ML model.
How the ground truth for the training set was established:
As there is no described "training set" in the context of an AI/ML model, this question is not applicable. The assay's development would be based on biochemical and immunological principles, and calibration/validation would use characterized positive and negative controls.

Summary

Regulation Number and Section

§ 866.3040

Aspergillus spp. serological reagents.(a)
Identification. Aspergillus spp. serological reagents are devices that consist of antigens and antisera used in various serological tests to identify antibodies toAspergillus spp. in serum. The identification aids in the diagnosis of aspergillosis caused by fungi belonging to the genusAspergillus. Aspergillosis is a disease marked by inflammatory granulomatous (tumor-like) lessions in the skin, ear, eyeball cavity, nasal sinuses, lungs, and occasionally the bones.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.