Search Results

The Optilite Freelite Kappa Free Kit is intended for the quantitative in vitro measurement of Kappa free light chains in serum using the Binding Site Optilite analyser. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenström's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE), and aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.

The Optilite Freelite Lambda Free Kit is intended for the quantitative in vitro measurement of Lambda in serum using the Binding Site Optilite analyser. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma, lymphocytic neoplasms, Waldenstrom's macroglobulinaemia, AL amyloidosis, light chain deposition disease and connective tissue diseases such as systemic lupus erythematosus (SLE), and aids in the evaluation of monoclonal gammopathy of undetermined significance (MGUS). Results of the free light chain measurements should always be interpreted in conjunction with other laboratory and clinical findings.

The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Optilite Freelite Kappa Free Kit and Optilite Freelite Lambda Free Kit:

Context: This submission is for a modification to a previously cleared device (K150658) to extend its indications for use to "aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS)". The core device technology and its principles (immunoturbidimetry for quantitative measurement of free light chains) remain unchanged. Therefore, the performance data provided specifically addresses the new MGUS claim.

Acceptance Criteria and Reported Device Performance

Device: Optilite® Freelite® Kappa Free Kit and Optilite® Freelite® Lambda Free Kit

Intended Use Extension: Aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS).

Study Details:

1. Sample Sizes and Data Provenance:

• Study 1 (Sensitivity and Specificity):
  • MGUS Samples (Sensitivity): 234 samples from patients with clinically confirmed MGUS.
  • Disease Controls (Specificity): 140 samples from patients with polyclonal hypergammaglobulinemia (non-MGUS).
  • Data Provenance: Retrospective testing of residual samples. The country of origin is not explicitly stated, but the company (The Binding Site Ltd.) is based in the United Kingdom.
• Study 2 (MGUS Progression):
  • Total Samples: 185 samples from 49 MGUS patients (45 stable, 4 progressive). Up to 4 individual sample draws for stable, up to 6 for progressive per patient.
  • Data Provenance: Retrospective testing of residual samples. Country of origin not explicitly stated.

2. Number of Experts and Qualifications for Ground Truth:

• The document states that the clinical diagnostic criteria that clinicians used to establish the "clinical truth" of MGUS positive samples were confirmed with each site.
• The ground truth for non-MGUS samples was based on "clinically confirmed polyclonal hypergammaglobulinemia" and "supporting clinical information."
• For the progression study, "clinically determined stable or progressive status" was the basis.
• The number of experts and their specific qualifications (e.g., radiologist with 10 years of experience) are not explicitly provided in the summary. It generally refers to "clinicians" and "clinical diagnosis."

3. Adjudication Method for the Test Set:

• Not explicitly mentioned. Given that the ground truth relies on "clinical diagnosis" and "clinically confirmed MGUS," it implies that the diagnostic criteria were applied by the treating clinicians at the respective sites prior to the retrospective study. There is no indication of an independent multi-expert adjudication process specifically for this study's test set.

4. MRMC Comparative Effectiveness Study:

• No. This submission is for an in-vitro diagnostic (IVD) device (a laboratory test), not an AI-assisted diagnostic tool that would directly assist human readers in image interpretation. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study to measure improvement in human readers with AI assistance is not applicable and was not performed.

5. Standalone Performance (Algorithm Only without Human-in-the-Loop):

• Yes. The study evaluates the performance of the device (Optilite Freelite Kappa and Lambda Free Kits on the Optilite Analyser) in measuring FLC levels and deriving the kappa:lambda ratio. The performance metrics (sensitivity, specificity, categorization of stable/progressive) are reported for the device's output itself, compared to the clinical ground truth. This is a standalone performance assessment of the IVD test.

6. Type of Ground Truth Used:

• Clinical Diagnosis / Clinical Findings:
  • For MGUS positive samples: "clinically confirmed MGUS" based on diagnostic criteria, including those outlined by the 'International Myeloma Working Group (IMWG)' consensus.
  • For non-MGUS samples: "polyclonal hypergammaglobulinemia confirmed by study testing (total IgG/lgA/lgM and serum IFE), with supporting clinical information."
  • For stable/progressive MGUS: "clinically determined stable or progressive status" based on patient follow-up and conversion to MM or stable status over time. This includes evaluation criteria based on IMWG guidelines for multiple myeloma regarding FLC changes.

7. Sample Size for the Training Set:

• Not applicable. This submission focuses on the performance of a lab-based immunoassay kit, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The test method is immunoturbidimetry, which relies on chemical reactions and optical detection, not an algorithm that learns from data.

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

• Not applicable, as there is no "training set" for this type of device. The method is a validated laboratory assay.

Ask a specific question about this device

This kit is intended for measuring human Immunoglobulin D (IgD) in serum as an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Not Found

This appears to be a 510(k) clearance letter from the FDA for a medical device. This type of document typically approves a device based on its substantial equivalence to a predicate device, rather than detailing a specific study and its acceptance criteria for a novel device or AI algorithm.

Therefore, the requested information regarding acceptance criteria, specific studies, sample sizes, expert involvement, and ground truth establishment, as it would apply to a typical pre-market approval (PMA) or a new AI/software as a medical device (SaMD) submission, is not present in this document.

Here's why and what we can infer:

• 510(k) Clearance: This is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed predicate device. The primary focus is on demonstrating equivalence, not necessarily on proving performance against predefined acceptance criteria for a novel technology through extensive new clinical trials.
• "Human IgD Liquid Reagent Kit for use on the Behring BNII Analyzer": This is an in-vitro diagnostic (IVD) kit. For IVDs, substantial equivalence often involves demonstrating comparable analytical and clinical performance to an already cleared predicate device. This would typically involve studies on:
  • Analytical Performance: Precision, accuracy, linearity, limit of detection, limit of quantitation, analytical specificity (interference, cross-reactivity).
  • Clinical Performance: Correlation to a predicate method using patient samples or clinical utility in diagnosis, but often not in the same rigorous blinded, multi-reader, prospective fashion as a novel diagnostic imaging AI.

Despite the lack of specific details, I can address your request based on the typical practices for such a device and what might have been included in the full 510(k) application (which is not provided here).

Hypothetical Description of Acceptance Criteria and Study (Based on Typical IVD 510(k) Requirements)

Given that this is an In-Vitro Diagnostic (IVD) device (a reagent kit), the acceptance criteria would typically focus on analytical performance metrics and concordance with a predicate device or an established gold standard.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance

• Test Set (for performance validation): Typically, clinical validation for an IVD 510(k) might involve anywhere from 100 to 500 patient samples to compare against a predicate or reference method. Additional samples would be used for analytical studies (e.g., dilution series, spiked samples, interference panels).
• Data Provenance: The data would almost certainly be retrospective for comparison studies, possibly with a smaller prospective component (e.g., for method comparison on fresh samples). Given The Binding Site is a UK-based company (though the letter is to a US representative), it's plausible the data could have originated from multiple countries, including the UK and the US, or from sites that supplied samples to the manufacturer for testing.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

For an IgD assay, the "ground truth" isn't typically established by a panel of human experts in the same way an image interpretation might be.

• Ground Truth for IVDs: The ground truth for quantitative assays like this is usually established by:
  • Reference Methods: Highly accurate, often more laborious or less accessible, laboratory methods (e.g., nephelometry using a specific calibrator, or potentially a standardized ELISA method).
  • Predicate Device Results: For a 510(k), the predicate device's results on the same samples would serve as the primary "ground truth" for demonstrating substantial equivalence.
  • Clinical Diagnosis: For evaluating clinical utility, patient samples would be selected based on confirmed clinical diagnoses (e.g., from patient charts adjudicated by a pathologist or clinical immunologist), and then the IgD levels would be correlated with these diagnoses. The number of such "experts" would be the clinicians/pathologists involved in the original patient diagnosis, not necessarily a panel specifically created for the device study.

4. Adjudication method for the test set

• Not applicable in the traditional sense. Since the device measures a quantitative analyte, "adjudication" wouldn't be done by multiple readers reviewing the device's output. Instead, it would involve:
  • Statistical comparison: Statistical methods (e.g., Bland-Altman analysis, regression analysis, percent agreement for categorical results) would be used to compare the device's results to the reference method or predicate device.
  • QC interpretation: Laboratory professionals would review quality control data to ensure runs are valid.

5. 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

• Not applicable. This device is an in-vitro diagnostic reagent kit for measuring a specific protein (Immunoglobulin D). It is not an AI-powered diagnostic imaging tool or a system designed to assist human readers (e.g., radiologists) in interpreting complex data. Therefore, an MRMC study and the concept of "human readers improving with AI" are not relevant to this type of device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, by nature. An IVD kit on an automated analyzer like the Behring BNII is designed to provide a quantitative result (an IgD concentration) based on reagents and instrumentation, without human interpretation of the "performance" of an algorithm in the sense of a diagnostic decision. The result is generated by the analytical process, and then a human interprets that numerical result in a clinical context.

7. The type of ground truth used

• Reference Method / Predicate Device Results. For this type of IVD, the ground truth for the measured IgD concentration would be established by:
  • Testing the same samples on a legally marketed predicate device (e.g., another FDA-cleared IgD assay).
  • Using a highly characterized reference laboratory method or a calibrated reference material for accuracy studies.
• Clinical Outcomes Data/Pathology: While these define the relevance of IgD levels (e.g., high IgD associated with certain conditions), they are generally not the direct "ground truth" for the measurement of IgD itself. The device measures the analyte; clinicians use that measurement in conjunction with pathology and other outcomes to form a diagnosis.

8. The sample size for the training set

• Not explicitly applicable in the AI sense. This is a reagent kit, not an AI algorithm that undergoes "training." The development would involve analytical characterization using various buffers, spiked samples, and potentially a diverse set of real patient samples to optimize the reagent formulation and assay parameters. The sample sizes for these development/optimization phases are part of the manufacturer's internal R&D process and wouldn't be termed "training sets" in the machine learning context.

9. How the ground truth for the training set was established

• Not applicable as an "AI training set." If we were to interpret "training set" as the samples used during assay development and optimization, the "ground truth" for these samples would be established through:
  • Known concentrations: For spiked samples or linearity studies.
  • Reference method results: For native patient samples to ensure the new assay correlates well with established methods during its development.
  • Characterized patient samples: Samples from patients with known IgD-related conditions or from healthy individuals to ensure the assay performs as expected across the relevant clinical range.

Ask a specific question about this device