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The Platelia™ Aspergillus EIA is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum and Bronchoalveolar Lavage (BAL) fluid samples.

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.

The Platelia™ Aspergillus EIA is a one-stage immunoenzymatic sandwich microplate assay which detects galactomannan in human serum and BAL fluid samples. The assay uses rat EBA-2 monoclonal antibodies, which are directed against Aspergillus galactomannan, and have been characterized in previous studies. The monoclonal antibodies are used, (1) to coat the wells of the microplate and bind the antigen, and (2) to detect the antigen bound to the sensitized microplate reagent: peroxidase-linked monoclonal antibodies).

Serum or BAL fluid samples are heat-treated in the presence of EDTA in order to dissociate immune complexes and to precipitate proteins that could possibly interfere with the test. The treated samples and conjugate are added to the wells coated with monoclonal antibodies, and incubated. A monoclonal antibody - galactomannan monoclonal antibody / peroxidase complex is formed in the presence of galactomannan 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 absorbance (optical density) of specimens and controls is determined with a spectrophotometer set at 450 and 620/630 nm wavelength.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device: Platelia™ Aspergillus EIA (Catalog 62793)
Intended Use: Immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum and Bronchoalveolar Lavage (BAL) fluid samples, as an aid in the diagnosis of Invasive Aspergillosis when used with other diagnostic procedures.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity and specificity. Instead, it presents the performance results. Assuming the "reported device performance" are the de facto acceptance criteria for this 510(k) submission, here are the key performance metrics:

The acceptance criteria appear to be implicitly defined by the sponsor's demonstration of these performance characteristics, particularly with confidence intervals, which indicate variability.

2. Sample Size Used for the Test Set and Data Provenance

• Serum Samples:

  • Pediatric Patients: 1954 serum samples from 129 immunocompromised pediatric patients (age ≤ 21 years) at high risk for Invasive Aspergillosis (IA), covering those diagnosed with Proven and Probable IA and controls.
    • Controls: 1625 serum samples from 108 pediatric patients.
    • IA Diagnosed: 249 serum samples from 17 pediatric patients.
  • Adult Patients: 1724 serum samples from 172 bone marrow transplant (BMT) and leukemic patients, covering those diagnosed with and without IA.
    • Controls: 1262 serum samples from 143 adult patients.
    • IA Diagnosed: 462 serum samples from 29 adult patients.
  • Provenance: "three testing centers in the United States" for pediatric studies and "three testing centers in North America" for adult studies. The studies are described as clinical studies, implying prospective collection of samples related to patient diagnosis/monitoring.

• BAL Fluid Samples:

  • Study 1 (SOT & Lung Transplant): 449 BAL samples from 178 Solid Organ Transplant (SOT) and lung transplant recipients.
    • Controls: 403 BAL samples from 167 SOT and lung transplant recipients (United States).
    • IA Diagnosed (SOT): 5 recipients.
    • IA Diagnosed (Lung): 6 recipients.
  • Study 2 (Hematology Patients): 99 evaluable BAL samples from 99 high-risk hematology patients.
    • IA Diagnosed: 58 patients.
    • Controls: 41 patients.
  • Provenance: Two studies from the "United States" (SOT & Lung Transplant) and one "retrospective analysis... from a study outside the United States" (Hematology Patients).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts used to establish the ground truth. It states that diagnoses of Invasive Aspergillosis (Proven or Probable) were defined by EORTC/NIAID definitions. This implies that the ground truth was established based on these standardized clinical and microbiological criteria, likely applied by clinical specialists at the participating sites, rather than an independent panel of experts reviewing cases.

4. Adjudication Method for the Test Set

The document does not describe a specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth. The reliance on EORTC/NIAID definitions suggests a criteria-based diagnosis rather than a read-by-committee adjudication process.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The studies evaluate the performance of the device itself (standalone algorithm) against a clinical diagnosis (ground truth), not in a human-in-the-loop context or comparing human reader performance with and without AI assistance.

6. Standalone Performance Study

Yes, a standalone (algorithm only without human-in-the-loop performance) study was done. The entire performance evaluation section describes the sensitivity and specificity of the Platelia™ Aspergillus EIA (the device/algorithm) when tested against various patient samples. The results presented are exclusively based on the device's output (index values) compared to the patient's clinical diagnosis.

7. Type of Ground Truth Used

The ground truth used was clinical diagnosis based on established criteria, specifically the Invasive Fungal Infection Cooperative Group (IFICG) of the European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) of the National Institute of Allergy and Infectious Diseases (NIAID) definitions for Proven and Probable Invasive Aspergillosis. Controls were defined as patients without signs of Invasive Aspergillosis.

8. Sample Size for the Training Set

The document does not mention a separate training set or its sample size. The provided performance evaluation focuses entirely on the "test set" or clinical validation set. Based on the context, this device is a laboratory assay, not a machine learning algorithm requiring a distinct training phase in the same way an AI imaging algorithm might. The reproducibility studies detail the use of "panel members" which are likely used for internal quality control and assay validation, but not a "training set" in the context of developing an AI model.

9. How the Ground Truth for the Training Set Was Established

As no specific training set for an AI model is described, this question is not applicable. The device is a diagnostic assay, and its development would typically involve assay design, optimization, and analytical validation rather than an AI training process.

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The Platelia™ Aspergillus EIA is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum samples.

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.

The Platelia™ Aspergillus EIA is a one-stage immunoenzymatic sandwich microplate assay which detects galactomannan in human serum. The assay uses rat EBA-2 monoclonal antibodies, which are directed against Aspergillus galactomannan, and have been characterized in previous studies 19,16. The monoclonal antibodies are used to coat the wells of the microplate and bind the antigen, and to detect the antigen bound to the sensitized microplate (conjugate reagent: peroxidase-linked monoclonal antibodies).

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 antibodies, and incubated. A monoclonal antibody - galactomannan - monoclonal antibody / peroxidase complex is formed in the presence of galactomannan 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 absorbance (optical density) of specimens and controls is determined with a spectrophotometer set at 450 and 620/630 nm wavelength.

Here's a summary of the acceptance criteria and study details for the Bio-Rad Platelia™ Aspergillus EIA, extracted from the provided 510(k) summary:

Acceptance Criteria and Device Performance:

Note: The document implies acceptance criteria by presenting performance data within clinical contexts and stating that the device is "substantially equivalent" to a predicate device, which inherently means it meets similar performance standards.

Study Details:

1. Sample Sizes and Data Provenance (Test Set):

   • Pediatric (new study for this submission):
     • Total Patients: 129 immunocompromised pediatric patients.
     • Total Samples: 1954 serum samples.
     • Invasive Aspergillosis (IA) Patients: 17 (9 Proven, 8 Probable).
     • Control/Non-IA Patients: 108 (from whom 1625 samples were tested).
     • Data Provenance: United States (three testing centers).
     • Retrospective/Prospective: Not explicitly stated, but the collection of patients diagnosed with IA and controls suggests it could be a mix or primarily retrospective given the diagnostic criteria often established over time.
   • Adult (previously conducted study for K023857):
     • Total Patients: 172 bone marrow transplant (BMT) and leukemic patients.
     • Total Samples: 1724 serum samples.
     • Invasive Aspergillosis (IA) Patients: 29 (11 Proven, 18 Probable).
     • Control/Non-IA Patients: 143 (from whom 1262 samples were tested).
     • Data Provenance: North America (three testing centers).
     • Retrospective/Prospective: Not explicitly stated, likely retrospective as it refers to a "previously conducted" study with diagnosed patients.

2. Number of Experts and Qualifications (Ground Truth for Test Set):

   • The ground truth for Invasive Aspergillosis (IA) was established based on EORTC/NIAID definitions. These definitions are rigorous and rely on a combination of:
     • Proven IA: Positive microbiological culture from a sterile site AND histopathological demonstration of fungal forms.
     • Probable IA: At least one microbiological criterion AND one major or two minor clinical criteria.
   • The document does not specify the number or qualifications of individual experts who applied these definitions to each patient/sample. It relies on the widely accepted, expert-consensus-derived EORTC/NIAID criteria.

3. Adjudication Method (Test Set):

   • The document does not explicitly state an adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of IA. The reliance on EORTC/NIAID definitions suggests a standardized, objective application of these criteria, which may involve review by treating clinicians or infectious disease specialists as part of the diagnostic process.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay designed to detect a biomarker (galactomannan antigen). Its performance is evaluated biochemically (sensitivity, specificity, reproducibility) rather than by human readers interpreting outputs, so a study comparing human reader performance with and without AI assistance is not applicable.

5. Standalone Performance Study (Algorithm Only):

   • Yes, this is a standalone performance study of the diagnostic assay. The "Performance Evaluation Studies" sections detail the assay's sensitivity and specificity based on its direct measurements of galactomannan antigen in serum, independent of human interpretation or a human-in-the-loop scenario.
   • The reproducibility and cross-reactivity studies also evaluate the algorithm's intrinsic performance.

6. Type of Ground Truth Used:

   • The ground truth used was "Proven or Probable Invasive Aspergillosis" as defined by EORTC/NIAID definitions. This is a robust clinical standard for diagnosing IA, incorporating:
     • Pathology: Histological examination of biopsy samples.
     • Microbiological culture: Positive culture from sterile sites.
     • Clinical evidence/outcomes data: Major/minor clinical criteria defined by the EORTC/NIAID.

7. Sample Size for the Training Set:

   • The document does not explicitly describe a separate "training set" in the context of an algorithm that learns from data.
   • This is an enzymatic immunoassay (EIA) kit, a traditional IVD device. The development and calibration of such a kit typically involve internal studies and optimization (analogous to "training" in AI), but these details are not provided as a distinct "training set" and "validation set" in the way they would be for a software algorithm. The performance evaluation discussed in the 510(k) is essentially the validation of the finalized assay itself.

8. How Ground Truth for the Training Set Was Established:

   • As there isn't a traditional "training set" for an AI algorithm in this context, the question of its ground truth establishment is not directly applicable.
   • For the initial development and optimization of the Platelia™ Aspergillus EIA (which would be analogous to "training"), the ground truth for positive and negative controls would have been established through well-characterized samples (e.g., purified galactomannan antigens, sera from confirmed IA patients, sera from healthy controls) using established reference methods and standards. However, these specific details for the "training" phase are not presented in this 510(k) summary.

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