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Optilite® Freelite Mx Kappa Free Kit:
The Optilite Freelite Mx Kappa Free Kit is intended for the quantitative in vitro measurement of Kappa free light chains in serum and urine using the Binding Site Optilite analyser. Measurement of free light chains in serum and urine 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 in serum 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.

Optilite® Freelite Mx Lambda Free Kit:
The Optilite Freelite Mx Lambda Free Kit is intended for the quantitative in vitro measurement of Lambda free light chains in serum and urine using the Binding Site Optilite analyser. Measurement of free light chains in serum and urine 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 in serum 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.

The provided FDA 510(k) clearance letter and its associated 510(k) Summary pertains to the Optilite Freelite Mx Kappa Free Kit and Optilite Freelite Mx Lambda Free Kit. The submission sought to add a claim for the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS) to the intended use statement (in serum).

Here's an analysis of the acceptance criteria and the study proving the device meets these criteria, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list acceptance criteria in terms of pre-defined numerical thresholds for sensitivity, specificity, or positive/negative rates that were required to be met for the MGUS claim. Instead, it describes clinical performance studies designed to demonstrate the utility of the device for MGUS evaluation. The conclusion states that "The studies generated successful results where all pre-defined acceptance criteria were met," implying these criteria were internal to the manufacturer's study design and not explicitly detailed in the public document as numerical targets.

However, we can infer the de facto "reported device performance" based on the results of Study 1 and Study 2.

Inferred Performance/Results:

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

• Study 1 (Evaluation of MGUS and disease controls at single time points):

  • MGUS Test Set: 229 samples from patients with clinically confirmed MGUS.
  • Disease Control Test Set (non-MGUS): 136 samples from patients with polyclonal hypergammaglobulinemia.
  • Provenance: Retrospective study. The country of origin is not explicitly stated, but the submitter (The Binding Site Ltd) is based in the United Kingdom.

• Study 2 (Evaluation of MGUS progression):

  • Total Patients: 49 MGUS patients.
    • Stable MGUS Cohort: 45 patients.
    • Progressive MGUS Cohort: 4 patients (who progressed from MGUS to MM).
  • Total Samples: 185 samples (up to 4 individual draws for stable, up to 6 for progressive).
  • Provenance: Retrospective study. Country of origin not explicitly stated.

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

• The document states that the clinical diagnostic criteria for MGUS and disease controls were "confirmed with each site" and "as practiced clinically."
• For the progressive MGUS study, changes were defined as clinical progression from MGUS to MM.
• No specific number of experts or their qualifications (e.g., "Radiologist with 10 years of experience") are mentioned in the provided text. The ground truth relies on "clinical diagnosis" or "clinical truth," which typically implies the consensus opinion of treating clinicians or established diagnostic criteria within the medical community (e.g., IMWG guidelines for MGUS/MM).

4. Adjudication Method for the Test Set

• The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the clinical ground truth. It relies on "clinical diagnosis" or "clinical truth" established by the sites providing the samples.

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

• No MRMC study was done. This device is an in vitro diagnostic (IVD) kit for quantitative measurement of biomarkers, not an image-based AI device that would typically involve human readers interpreting images. The closest analog would be a clinical utility study comparing outcomes with and without the FLC test, but that is beyond the scope of a 510(k) for an IVD kit unless explicitly requested for a novel claim.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• This is a standalone study. The Optilite Freelite Mx Kappa and Lambda Free Kits are laboratory assays. The "performance data" presented (positive rates, negative rates, tracking of progression) are derived solely from the measurements made by the device (Optilite Analyser) on patient samples, compared against established clinical diagnoses (ground truth). There is no "human-in-the-loop" aspect to the device's direct measurement and result generation. The results are then interpreted by clinicians in conjunction with other findings, but the device's output itself is standalone.

7. Type of Ground Truth Used

• The ground truth used was clinical diagnosis/clinical truth.
  • For Study 1: "clinically confirmed MGUS" and "polyclonal hypergammaglobulinemia confirmed by study testing... with supporting clinical information." The diagnostic criteria for MGUS were stated to align with or be similar to those outlined by the International Myeloma Working Group (IMWG).
  • For Study 2: "clinically determined stable or progressive status" for MGUS patients, with progression defined as conversion from MGUS to Multiple Myeloma (MM) based on clinical diagnosis. FLC results criteria adapted from IMWG guidelines were used for evaluation of the device's performance, but the patient's status (stable/progressive) was the "clinical diagnosis."

8. Sample Size for the Training Set

• The document states, "The devices in this submission have not materially changed since originally cleared under K150658." This implies that the core analytical performance studies (e.g., analytical measuring range, precision, accuracy) were previously established and referenced from prior 510(k) submissions (K173732 and K150658).
• For the new MGUS claim, the performance data presented are for clinical validation on the test sets described in points 1 and 2.
• The document does not describe a distinct "training set" for the clinical claim of MGUS evaluation, nor is it typical for IVD kits to have a "training set" in the machine learning sense for their clinical claims. The performance studies demonstrate the device's ability to measure FLCs in patient populations relevant to MGUS, and these measures are compared against clinical ground truth. The assay itself (reagents, instrument) would have been "trained" (i.e., optimized and validated analytically) during its initial development and previous clearances.

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

• As a "training set" for the clinical claim is not explicitly mentioned or relevant for this type of IVD 510(k), this question is not directly applicable. For the device itself, analytical validation and calibration would have established its operational parameters, but this isn't "ground truth" in the diagnostic performance sense. The clinical ground truth for the test sets was derived from established clinical diagnoses and diagnostic criteria.

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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.

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This kit is intended for the quantitative in vitro determination of human IgA in serum, lithium heparin or EDTA plasma, using the Binding Site SPAPLUS turbidimetric analyser. Measurement of IgA aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

Human IqA liquid reagent kit for use on SPAPLUS® comprises the following reagents:

Antiserum: Monospecific goat anti IgA supplied in stabilised liquid form. lt contains 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine as preservatives.

Calibrator and Controls: These consist of pooled human serum and are supplied in stabilised liquid form. The concentration of IgA given on the quality control certificate has been obtained by comparison with European Reference Material ERM-DA470k. They contain 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives.

Reaction Buffer: Containing 0.099% sodium azide as a preservative.

The provided document describes the "Human IgA liquid reagent kit for use on SPAPLUS" by The Binding Site Group Ltd. This device is intended for the quantitative in vitro determination of human IgA in serum, lithium heparin, or EDTA plasma using the Binding Site SPAPLUS turbidimetric analyzer. The submission is a special 510(k) for a modification to an existing device (K103824), specifically a change in the source of the detection antibody from sheep to goat.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present acceptance criteria in a dedicated table format with corresponding reported device performance for all aspects. Instead, acceptance criteria are described within the context of each study and then a conclusion about meeting those criteria is stated. I will extract and present this information in a table format where possible.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Precision Studies:
  • Repeatability and Within Laboratory: 4 different samples, 80 data points for each level (total 320 data points).
  • Between Instrument: 4 different samples, 24 data points for each level (total 96 data points).
  • Between Lot: 4 different samples, 24 data points for each level (total 96 data points).
• Linearity Study: A high pool (8.19g/L) and a low pool (0.12 g/L) were used to create a dilution series. Each diluted sample was tested in 3 replicates.
• Accelerated Stability: 6 replicates of controls, internal reference, and 3 different samples were tested.
• Limit of Quantitation (LoQ) Validation: 4 samples were tested using two reagent lots.
• Method Comparison with Predicate Device: 102 serum samples and 42 plasma samples (total 144 samples).
• Expected Values/Reference Range Transfer: 20 samples from "apparently healthy US donors".

Data Provenance:

• For the Expected Values/Reference Range Transfer study, samples were from "apparently healthy US donors".
• For other studies, the country of origin or whether the data was retrospective or prospective is not explicitly stated. The studies were carried out by The Binding Site Group Ltd., which is based in the UK, so it's likely testing was conducted there unless otherwise specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This product is an in vitro diagnostic (IVD) reagent kit for quantitative Immunoglobulin A (IgA) determination. The "ground truth" in this context refers to the accurate measurement of IgA concentration. The document mentions traceability to European Reference Material ERM-DA470k/IFCC for calibration. This implies that the standard itself serves as the "ground truth" reference, rather than independent expert consensus on clinical interpretation. There are no mentions of experts establishing ground truth in the sense of clinical diagnosis or image interpretation.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretation by multiple human readers (e.g., in radiology studies) to resolve discrepancies and establish a consensus "ground truth." Since this device is a quantitative IVD assay and its performance is validated against analytical standards, reference materials, and comparative measurements, such adjudication methods are not applicable and therefore not used.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for AI-powered diagnostic tools where human readers (e.g., radiologists) use AI assistance to improve their diagnostic accuracy. This device is a standalone quantitative laboratory test kit, not an AI or imaging diagnostic aid, so an MRMC study is not applicable.

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

Yes, the performance studies described are for the standalone device (reagent kit on the SPAPLUS analyzer) without human-in-the-loop performance influencing the measurement part of the device's function. The analytical performance, stability, and comparison studies evaluate the kit's ability to accurately measure IgA concentrations. The device's output is a quantitative value, not an interpretation of data that requires human feedback for performance assessment.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for this quantitative assay is primarily based on:

• Reference Materials: Calibration traceability to ERM-DA470k/IFCC. This is the international standard for immunoglobulin measurements.
• Reference Methods: The predicate device itself (K103824) serves as a comparative "ground truth" for method comparison studies, demonstrating substantial equivalence.
• Defined Concentrations: For linearity and precision studies, samples with known or precisely diluted concentrations are used.
• Clinical Reference Intervals: The ability to transfer established reference intervals (based on a healthy population) is also part of the "ground truth" for clinical usability.

8. The sample size for the training set

This document describes a special 510(k) submission for a modification to an existing device, which mostly involves re-validation studies to ensure the modification (change in antibody source from sheep to goat) does not alter performance compared to the cleared predicate. It does not describe the development of a novel algorithm or AI model that requires a distinct "training set." The studies performed are validation studies, not training. Therefore, a "training set" in the context of machine learning is not applicable here.

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

As there is no "training set" in the machine learning sense for this device submission, this question is not applicable. The device's underlying principles (immunoturbidimetry) are well-established, and its performance is validated against analytical standards rather than learned from a dataset.

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The Optilite IgA Kit is intended for the quantitative in vitro measurement of IgA in serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgA aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other laboratory and clinical findings.

The Optilite IgA Kit comprises the following reagents: Antiserum: Goat anti IgA supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine. Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material. Reaction Buffer: Containing 0.099% sodium azide as a preservative.

Here's a breakdown of the acceptance criteria and study detailed in the provided document for the Optilite IgA Kit, organized according to your requested information.

It's important to note that this document is a 510(k) summary for a modification to an existing device (Optilite IgA Kit, K103824). Therefore, the study presented here primarily focuses on confirming that the modified device (with a change from sheep to goat antibody) performs comparably to the predicate device (the original cleared kit) and that the performance characteristics detailed in the original submission still hold true. This is not a study to establish initial performance characteristics, but rather to demonstrate equivalence after a modification.

Acceptance Criteria and Device Performance Study for Optilite IgA Kit (K191985)

This study was conducted to demonstrate that the modified Optilite IgA Kit, with a change in the source of the detection antibody from sheep to goat, maintains comparable performance to the predicate device (Optilite IgA Kit, K103824). The acceptance criteria were primarily based on demonstrating no significant change in performance compared to the previously cleared device.

1. Table of Acceptance Criteria and Reported Device Performance

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The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnomal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

The Optilite IgM Kit comprises the following reagents: Antiserum: Goat anti IgM supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine. Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material. Reaction Buffer: Containing 0.099% sodium azide as a preservative.

The provided text describes a 510(k) submission for the Optilite IgM Kit, which is a quantitative in vitro measurement system for IgM in human serum, lithium heparin, or EDTA plasma. The submission is a modification to an existing device (K082129). The core of the submission revolves around demonstrating that the modified device maintains performance comparable to the previously cleared device, rather than proving initial efficacy or diagnostic accuracy.

Based on the provided text, here's an analysis of the acceptance criteria and study proving the device meets them:

Key Takeaway: This 510(k) submission is for a modification to an existing device (change of antibody source and buffer). Therefore, the "acceptance criteria" and "study" are primarily focused on demonstrating that this modification does not negatively impact the performance compared to the original, already cleared device. There is no new clinical effectiveness study to establish diagnostic accuracy against a disease state from scratch.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally framed as "no change in performance compared to the device cleared in K082129" or meeting specific pre-defined quantitative thresholds (e.g., allowable CV, limits of agreement).

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

• Precision Studies (Repeatability and Within Laboratory):
  • Sample Size: 5 different samples. For each level, N=80 for Repeatability/Within Lab Summary (20 working days * 2 runs/day * 2 reps/run).
  • Data Provenance: Not explicitly stated, but typically internal lab data (e.g., from the manufacturer's R&D or QC labs).
• Precision Studies (Between Instrument):
  • Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
  • Data Provenance: Not explicitly stated, typically internal lab data.
• Precision Studies (Between Lot):
  • Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
  • Data Provenance: Not explicitly stated, typically internal lab data.
• Linearity Study:
  • Sample Size: Dilution series from a high pool (8.44 g/L) and a low pool (0.17 g/L). Each diluted sample tested in 3 replicates.
  • Data Provenance: Not explicitly stated, typically internal lab data.
• Kit Stability (Accelerated):
  • Sample Size: 6 replicates of controls, internal reference, and samples.
  • Data Provenance: Not explicitly stated, typically internal lab data.
• Detection Limit (LoQ) Study:
  • Sample Size: Four samples.
  • Data Provenance: Not explicitly stated, typically internal lab data.
• Method Comparison with Predicate Device:
  • Sample Size: 120 serum samples and 60 plasma samples (total 180 samples).
  • Data Provenance: Not explicitly stated, but typically clinical samples or commercial samples purchased for the study. Given the medical context, these would be human samples. The study was conducted as per pre-submission meeting Q171503, implying a prospective design for this specific comparative testing.
• Expected Values/Reference Range:
  • Sample Size: 20 samples from apparently healthy US donors.
  • Data Provenance: Prospective collection of samples from US donors.

Overall Data Provenance: The document explicitly mentions "20 samples from apparently healthy US donors" for the reference range study. For other analytical performance studies (precision, linearity, stability, detection limit), the provenance is not specified, but these are typically conducted in-house by the manufacturer (retrospective analysis vs. new data collection is not detailed, but likely new data generation for the modified kit).

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

This device is an in vitro diagnostic (IVD) for quantitative measurement of IgM. The "ground truth" for IVDs of this nature is established by the reference measurement procedure or the assigned/target values of calibrators and controls used in the analytical performance studies, not by clinical expert consensus in the way a diagnostic imaging AI might establish ground truth from radiologists.

• For Analytical Studies (Precision, Linearity, LoD/LoQ, Stability): The ground truth for these samples are their known or reference concentrations, which are determined by highly accurate laboratory methods or traceable standards (e.g., ERM-DA470k/IFCC for IgM). No clinical experts are involved in establishing this type of ground truth.
• For Method Comparison: The "ground truth" in this context is the result obtained from the predicate device (the unmodified K082129 kit), as the goal is to show agreement between the modified and unmodified kit.
• For Reference Range Study: The "ground truth" is the established reference interval for IgM in a healthy population. The study assessed whether the modified kit's results for healthy individuals fell within this known range.

Therefore, the concept of "experts establishing ground truth" as it applies to reader studies for imaging devices does not directly apply here.

4. Adjudication Method for the Test Set

Given that this is an IVD kit for quantitative measurement and not an imaging device requiring human interpretation, there is no mention of an adjudication method among multiple human readers. The analytical performance is evaluated against quantitative measurements, established standards, or the performance of the predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. MRMC studies are specific to diagnostic performance, typically for imaging devices where multiple readers interpret cases with and without AI assistance. This submission is for an IVD kit that provides a quantitative measurement, not an interpretative diagnosis requiring human readers in the loop. The "comparison" done was a method comparison between the modified kit and the predicate kit.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, in essence. The "device" here is the Optilite IgM Kit used on the Optilite analyser. Its performance is evaluated analytically (precision, linearity, limits, stability) and comparatively against its predicate. This is a standalone performance assessment of the kit, which automatically provides quantitative results. There is no human interpretative step that the kit is assisting or replacing within its intended use.

7. The Type of Ground Truth Used

• For Analytical Performance (Precision, Linearity, LoD/LoQ, Stability):
  • Traceability: ERM-DA470k/IFCC (a certified reference material for immunoglobulins). This is a highly robust form of ground truth based on international standards.
  • Known Concentrations: Samples and controls with established or assigned target values.
• For Method Comparison:
  • Predicate Device Results: The results from the previously cleared Optilite IgM Kit (K082129) served as the reference for comparison to demonstrate equivalence.
• For Reference Range Study:
  • Established Reference Interval: The pre-determined reference range (0.35 – 2.42 g/L) for IgM in a healthy population served as the ground truth against which results from healthy donors were compared.

There is no pathology confirmation or outcomes data mentioned, as these are typically used for assessing clinical accuracy or impact on patient management, which is beyond the scope of this 510(k) for a modified quantitative IVD.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. This submission is for an immunoturbidimetric test kit, not an AI-powered diagnostic system. The "training" of such a system would refer to the development and optimization of the reagent formulation and methods, which involves extensive R&D and internal testing, often with many samples. However, the document provided focuses on the validation testing required for regulatory submission.

The section M. Performance Characteristics details the validation experiments for the modified kit. These are the test sets to prove performance, not training sets.

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

As noted above, there is no "training set" in the AI/ML sense described. For the development of the original device and its subsequent modifications, the "ground truth" would be established through:

• Reference materials: Calibrating the assay against international reference standards (e.g., ERM-DA470k/IFCC).
• Internal validation: Testing against well-characterized in-house samples and controls with known concentrations.
• Method optimization: Iteratively adjusting reagent concentrations and reaction parameters to achieve desired analytical performance (sensitivity, specificity, precision, linearity) based on these known samples and reference materials.

The provided document focuses on the verification and validation studies for a pre-defined modified product, demonstrating its performance against regulatory requirements, rather than the developmental phase of the original or modified kit's creation.

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This kit is intended for the quantitative in vitro determination of human IgM in human serum, lithium heparin or EDTA plasma, using the Binding Site SPAPLUS turbidimetric analyser. Measurement of IgM aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

The SPAPlus IgM Kit comprises the following reagents:

Antiserum: Goat Anti-IgM is supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine.

Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 0.099% sodium azide. 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material.

Reaction Buffer: Containing 0.099% sodium azide as a preservative.

The provided document (K191465 - Human IgM Kit for use on SPAPlus Special 510(k) Submission Summary) describes the analytical and performance characteristics of a quantitative in vitro diagnostic device, not an AI/ML-based medical device. Therefore, many of the questions regarding acceptance criteria for AI/ML performance, ground truth establishment by experts, MRMC studies, and training/test set details are not applicable.

This submission is for a modification to an existing device (Human IgM Kit for Use on SPAPlus, K082129), specifically changing the source of the detection antibody from sheep to goat and altering the antibody resting buffer. The primary goal of the studies presented is to demonstrate that these changes do not adversely affect the device's performance compared to the original cleared device and that the new kit is substantially equivalent.

Here's an attempt to answer the questions based on the available information, noting when a question is not applicable to this type of device:

Acceptance Criteria and Device Performance

1. A table of acceptance criteria and the reported device performance

Since this is a chemistry assay device, the "acceptance criteria" are more about demonstrating comparable performance to the predicate device and meeting established analytical performance standards for in vitro diagnostics rather than an AI/ML output metric like accuracy or AUC.

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Precision Studies:
  • Repeatability & Within Laboratory: 3 different samples, 80 replicates each (20 working days, 2 runs/day, 2 reps/run).
  • Between Instrument: 3 different samples, 24 replicates each (6 working days, 2 instruments/day, 2 reps/instrument).
  • Between Lot: 3 different samples, 24 replicates each (6 working days, 2 lots/day, 2 reps/lot).
  • Provenance: Not explicitly stated, but likely retrospective lab testing from the manufacturer (The Binding Site Group Ltd. in UK). Dates of testing are implied by "over 20 working days" etc.
• Linearity Study: High and low pools, dilution series, 6 replicates per diluted sample.
  • Provenance: Not explicitly stated, likely retrospective lab testing.
• Stability Studies:
  • Accelerated Stability: 6 replicates of controls, internal reference, and samples.
  • Provenance: Not explicitly stated, likely retrospective lab testing.
• Detection Limit (LoQ) Study: Four samples, two reagent lots.
  • Provenance: Not explicitly stated, likely retrospective lab testing.
• Method Comparison Study: 89 serum samples and 44 plasma samples.
  • Provenance: Performed "in accordance with pre-submission meeting Q171503." Not explicitly stated, but likely retrospective from clinical laboratories or biobanks.
• Reference Range Transfer Study: 20 samples from "apparently healthy US donors."
  • Provenance: Prospective collection from apparently healthy US donors appears to be implied given the mention of "US donors" and the purpose of transferring the reference interval.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is an in vitro diagnostic device that measures a quantitative analyte (IgM). "Ground truth" for this type of device is established by the analytical measurement itself, traceable to an international reference material (ERM-DA470k/IFCC). Clinical expert consensus is not a method for establishing the "ground truth" concentration of an analyte in a sample for this type of device.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. Adjudication methods like 2+1 or 3+1 are used for establishing ground truth in image interpretation or clinical diagnosis, often when human expert variability is a factor. This submission is for a turbidimetric assay, where the "ground truth" is a quantitative measurement traceable to a reference standard.

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 is not an AI/ML device and does not involve human readers interpreting images or data.

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

Not applicable. This is not an AI/ML device. The "performance" is the analytical performance of the assay itself.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

The "ground truth" for the quantitative measurement of IgM in this IVD is established by its traceability to a recognized international reference material (ERM-DA470k/IFCC). This standard provides the authoritative value for IgM concentration against which the device's measurements are calibrated and compared.

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a "training set" in the machine learning sense. The device is a "kit" of reagents and controls used on an analyser.

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

Not applicable (as above, no "training set" in the AI/ML sense). The calibration of the assay (which could be conceptually analogous to "training" a traditional assay) is traceable to ERM-DA470k/IFCC, an international reference material.

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The Optilite IgM CSF Kit is intended for the quantitative in vitro measurement of IgM in cerebrospinal fluid (CSF) samples using the Optilite analyser.

The Optilite IgM CSF Kit comprises the following reagents:
Latex Reagent: Supplied in stabilised liquid form. Preservatives: 0.025% sodium azide, 0.1% E-amino-n-caproic acid (EACA) and 0.01% benzamidine, 0.05% ProClin.
Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material.
Reaction Buffer: Containing 0.099% sodium azide as a preservative.

The provided text describes the 510(k) submission for the Optilite IgM CSF Kit, an in vitro diagnostic device, not an AI/ML-based device. Therefore, the questions related to AI/ML specific criteria, such as expert adjudication, MRMC studies, standalone algorithm performance, and training set details, are not applicable to this submission.

The acceptance criteria and device performance evaluation for this diagnostic kit are centered on analytical performance characteristics, which are standard for laboratory assays.

Here's a breakdown of the applicable information from the provided text:

1. Table of acceptance criteria and the reported device performance:

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The Optilite IgA CSF Kit is intended for the quantitative in vitro measurement of IgA in cerebrospinal fluid (CSF) using the Optilite analyser.

The Optilite IgA CSF Kit comprises the following reagents: Latex Reagent, Calibrator and Controls, and Reaction Buffer.

The provided text describes the performance characteristics of the Optilite IgA CSF Kit. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Precision/Reproducibility: 4 different samples were used. The number of runs (two per day for 5 days) and analysts (two) suggest multiple measurements for each sample. Data provenance is not explicitly stated but is implicitly from an internal laboratory study (prospective).
• Linearity: One serially diluted sample was used. Data provenance is implicitly from an internal laboratory study (prospective).
• Analytical Specificity: A CSF sample close to the medical decision point and an elevated CSF sample were tested. Data provenance is implicitly from an internal laboratory study (prospective).
• Method Comparison: 130 CSF samples (including 40 samples with analyte levels within the reference interval) were used. Data provenance is not explicitly stated, but it's likely from a collection of clinical samples. It is retrospective in nature as these are "samples" analyzed, not patients prospectively enrolled.

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

This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker. The "ground truth" for the test set is established by the reference methods or the true concentration of the analyte, not by expert interpretation in the same way an imaging or pathology device would involve human experts.

• For precision, the ground truth is the true concentration of IgA in the sample, measured repeatedly to assess variation.
• For linearity, the ground truth is the expected concentration based on the serial dilution.
• For traceability, the ground truth is the value assigned by the international reference material (ERM-DA470k/IFCC).
• For method comparison, the ground truth is the measurement obtained from the alternative commercially available assay (predicate device).

Therefore, the concept of "number of experts used" or their "qualifications" for establishing ground truth is not directly applicable in the context of this type of quantitative IVD performance study.

4. Adjudication Method for the Test Set

Not applicable. As a quantitative IVD, the results are numerical values, and adjudication by experts is not a standard practice for assessing performance metrics like precision, linearity, or method correlation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) to assess the impact of AI assistance on human performance. The Optilite IgA CSF Kit is a standalone automated quantitative assay, not an AI-assisted interpretation tool.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

Yes, the performance studies described are intrinsically standalone performance evaluations of the Optilite IgA CSF Kit (the "algorithm/device only" in this context) without human-in-the-loop performance. The device provides a quantitative measurement directly.

7. The Type of Ground Truth Used

• Precision and Linearity: The ground truth is based on the known or reference concentrations of the samples used in the study.
• Traceability: The ground truth is the value assigned by the international reference material (ERM-DA470k/IFCC).
• Method Comparison: The ground truth for comparative purposes is the result obtained from an alternative commercially available assay (predicate device).

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. This device is an in vitro diagnostic kit based on immunoturbidimetry, which is a chemical/biological reaction and measurement system, not a machine learning model that requires a training set. The term "training set" is not applicable here.

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

Not applicable, as there is no "training set" for this type of device.

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The Optilite High Sensitivity C-Reactive Protein Kit is intended for the quantitative in vitro measurement of C-Reactive Protein in serum using the Binding Site Optilite analyser for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. This test should be used in conjunction with other laboratory and clinical findings.

The Optilite High Sensitivity C-Reactive Protein Kit is comprised of latex reagent, single calibrator, controls (high and low) and reaction buffer in liquid form. The reagents contain 0.099% sodium azide as preservative.

Acceptance Criteria and Study for Optilite High Sensitivity C-Reactive Protein Kit

Here's a breakdown of the acceptance criteria and the study results for the Optilite High Sensitivity C-Reactive Protein Kit, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

• Method Comparison with Predicate Device: 391 serum samples (302 reported results within the measuring range). These included 87 normal donors and 304 clinical samples.
• Expected Values/Reference Range Verification: 50 adult donor samples.

Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective. Given "The Binding Site Group, Ltd." is based in the UK, it's highly probable that the studies were conducted there. The nature of the studies (e.g., precision, linearity, method comparison) generally implies prospective testing of samples for analytical performance, though the 304 "clinical samples" in the method comparison could be retrospective or a mix.

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

Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker (C-Reactive Protein). The "ground truth" for its performance is established through comparisons with reference methods, calibrated materials, and statistical analysis of assay performance (precision, linearity, detection limits), rather than through expert consensus on qualitative interpretation.

4. Adjudication Method for the Test Set:

Not applicable, as this is a quantitative IVD device. Test results are numerical and assessed against predefined analytical performance criteria, not subjective interpretations requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for AI-powered diagnostic imaging devices where human readers interpret images. The Optilite Kit is an automated immunoassay system, not an imaging device requiring human interpretation.

6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone study of the algorithm (the Optilite High Sensitivity C-Reactive Protein Kit and Optilite analyser) was performed. All the analytical performance characteristics (precision, linearity, detection limits, analytical specificity) and method comparison studies described are standalone evaluations of the device's performance without human intervention in the result generation process.

7. The Type of Ground Truth Used:

The ground truth for this device is established through:

• International Reference Standards: The assay is traceable to the international reference standard ERM-DA474 for calibration.
• Statistical Definitions: For precision (CV%), linearity (deviation from linearity), detection limits (LoB, LoD, LoQ), established statistical methodologies (CLSI EP5-A3, EP6-A, EP17-A2) define the acceptable "ground truth" or performance targets.
• Reference Methods/Predicate Device: For method comparison, the results from the legally marketed predicate device (C-Reactive Protein High Sensitive Test System for Cobas Integra Instruments) serve as the comparative "ground truth" for demonstrating substantial equivalence.
• Clinical Relevance: The reference interval (

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The Optilite Freelite Mx Kappa Free Kit is intended for the quantitative in vitro measurement of Kappa free light chains in serum and urine 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) in conjunction with other laboratory and clinical findings.

The Optilite Freelite Mx Lambda Free Kit is intended for the quantitative in vitro measurement of Lambda free light chains in serum and urine 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) in conjunction with other laboratory and clinical findings.

The Optilite Freelite Mx Kappa Free Kit is comprised of the following reagents: Latex Reagent: Sheep anti-Human Kappa (polyclonal monospecific) antibody (F(ab')2 fragment) bound to 200nm polystyrene latex particles. In 0.033M Glycine buffered saline pH8 (containing Sodium Azide (0.033%), Proclin (0.05%), Benzamidine (0.01%) and EACA (0.1%) as preservative plus BSA (0.033%)). Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. Reaction Buffer: Containing 0.099% sodium azide as a preservative.

The Optilite Freelite Mx Lambda Free Kit is comprised of the following reagents: Latex Reagent: Sheep anti-Human Lambda (polyclonal monospecific) Free antibody (F(ab')2 fragment) bound to 200nm polystyrene latex particles. In 0.033M Glycine buffered saline pH8 (containing Sodium Azide (0.033%), Proclin (0.05%), Benzamidine (0.01%) and EACA (0.1%) as preservatives plus BSA (0.1665%)). Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. Reaction Buffer: Containing 0.099% sodium azide as a preservative.

Note - In Optilite Freelite kits, the latex reagent and reaction buffer are supplied in a single wedge with a chamber for each fluid. They are therefore labelled as a single component Optilite Kappa Free Mx Reagent or Optilite Lambda Free Mx Reagent.

The provided text describes the performance characteristics of the Optilite Freelite Mx Kappa Free Kit and Optilite Freelite Mx Lambda Free Kit, which are devices for the quantitative measurement of Kappa and Lambda free light chains in serum and urine.

Here's an analysis of the acceptance criteria and the study that proves the device meets these criteria, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a submission for an in-vitro diagnostic device, the "acceptance criteria" are typically inferred from the performance targets set by the manufacturer and assessed against relevant CLSI (Clinical and Laboratory Standards Institute) guidelines. The reported device performance is directly stated in the tables within the document.

Precision/Reproducibility

Clinical Agreement (2x2 Table with Predicate)

Notes on Acceptance Criteria: The document does not explicitly state quantitative acceptance criteria or pass/fail thresholds for many of these performance metrics. The criteria listed above are inferred based on typical expectations for in-vitro diagnostic devices undergoing 510(k) clearance, often guided by CLSI guidelines. The FDA's substantial equivalence determination implies that the reported performance is acceptable in comparison to the predicate device and the recognized standards.

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

• Precision/Reproducibility:

  • Kappa: Four urine sample pools were tested. The testing involved 21 days with two runs per day using one reagent lot on three analyzers.
  • Lambda: Five urine sample pools were tested. The testing involved 23 days with two runs per day using one reagent lot on three analyzers.
  • Provenance: Not explicitly stated, but likely in-house (Binding Site Group Ltd.) and conducted under controlled laboratory conditions, given it's part of analytical performance testing for an IVD.

• Linearity/Assay Reportable Range:

  • Sample Size: "serially diluted urine samples" were used. The exact number of individual samples or dilutions is not specified.
  • Provenance: Not explicitly stated, but likely in-house.

• Detection Limit:

  • LoB: 60 determinations of blank samples (analyte depleted serum and urine at a low analyte concentration).
  • LoQ: Five independent samples (serum and urine) tested twelve times over five days.
  • Provenance: Not explicitly stated, but likely in-house.

• Analytical Specificity (Interference):

  • Sample Size: "a single urine sample for the Kappa Free assay and the Lambda Free assay". These were prepared with interferents.
  • Provenance: Not explicitly stated, but likely in-house.

• Method Comparison with Predicate Device:

  • Kappa Free: 165 urine samples (including 86 with analyte levels below the reference limit).
  • Lambda Free: 115 urine samples (including 59 with analyte levels below the reference limit).
  • Provenance: Not explicitly stated, but these are patient samples tested against a predicate device. Given the context of a European manufacturer and the lack of specific geographical mention, they could be from various locations or a specific clinic associated with the manufacturer. Retrospective or prospective is not specified, but typically for method comparison, collected samples are used retrospectively.

• Clinical Agreement (2x2 Table with Predicate):

  • Kappa: 166 samples (derived from the 2x2 table: 78+1+8+79 = 166, though the sum of listed cells is 166, the total is given as 166, implying a discrepancy in the row/column totals). The method comparison stated 165, so there might be a rounding or slight difference in sample inclusion for the clinical agreement vs. regression.
  • Lambda: 168 samples (derived from the 2x2 table totals). The method comparison stated 115. This suggests different sample sets or criteria for the 2x2 table analysis compared to the regression analysis, especially given the sample sizes below the reference limit quoted for the method comparison.
  • Provenance: Not explicitly stated, but presumed to be from clinical settings for patient samples. These are likely retrospective samples previously analyzed by the predicate.

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

For an in-vitro diagnostic device like this, "ground truth" and "experts" are typically not established in the same way as for imaging devices requiring expert interpretation.

• Ground Truth: For this device, the "ground truth" is typically the result obtained from a well-established, often reference, method or the predicate device that the new device is being compared against. In this case, the predicate device (Freelite® Human Kappa/Lambda Free Kit for use on the Siemens BN™II) serves as the comparator, from which the "Assay" results are compared.
• Experts and Qualifications: There is no mention of external experts being used for establishing ground truth. The evaluation relies on analytical and clinical performance studies comparing the new device against the predicate or established analytical standards.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

Not applicable for this type of in-vitro diagnostic device performance study. Adjudication methods like 2+1 or 3+1 are common in studies where human readers interpret medical images and their interpretations need to be reconciled to establish a ground truth or a consensus opinion. For IVD devices, the "truth" for comparison is usually defined by the results of a reference method or legally marketed predicate.

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. MRMC studies, and improvement with AI assistance, are relevant to medical imaging devices where human readers (e.g., radiologists) interpret images. This submission is for an in-vitro diagnostic assay for laboratory measurement of biomarkers, which does not involve human interpretation of complex visual data in the same way.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a standalone diagnostic assay (an "algorithm only" if one considers the assay chemistry and instrument processing as the "algorithm"). It performs quantitative measurements without direct human real-time interpretation influencing the numerical result. The human element is in collecting the sample, running the test, and interpreting the numerical result in a clinical context.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for comparative studies and assessment of substantial equivalence is primarily established by:

• Predicate Device Results: For method comparison and clinical agreement, the results from the legally marketed predicate device (Freelite® Human Kappa/Lambda Free Kit on the Siemens BN™II) are used as the reference ('ground truth') for comparison.
• CLSI Guidelines: For analytical performance (precision, linearity, detection limits, interference), the "ground truth" is defined by adherence to the methodologies and performance expectations outlined in recognized CLSI guidelines (e.g., EP17-A, EP7-A2, EP6-A, EP5-A2).

8. The Sample Size for the Training Set

This document does not specify a separate "training set" sample size in the context of machine learning. For IVD devices, development involves extensive internal testing and optimization (which can be considered analogous to "training"), but the provided document focuses on the validation studies. The studies described are primarily validation studies against regulatory requirements.

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

Given that this is an IVD kit based on turbidimetry, it doesn't involve a "training set" or "ground truth" in the machine learning sense. The "ground truth" during development (analogous to training) would involve using known concentrations of analytes, reference materials, and established analytical methods to ensure the assay performs as expected.

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