Search Results

The Access OV Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 125 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 125 antigen to aid in the management of ovarian cancer patients. Serial testing for patient CA 125 antigen concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

The Access OV Monitor assay is a sandwich immunoenzymatic assay. The Access OV Monitor assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access OV Monitor assay reagent pack, Access OV Monitor assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

The document provided is an FDA 510(k) clearance letter and a 510(k) summary for the Beckman Coulter Access OV Monitor assay. This device is an in vitro diagnostic (IVD) immunoassay for measuring CA 125 antigen levels to aid in the management of ovarian cancer patients.

The information requested pertains to the performance study design for AI/ML-based diagnostic devices, which is typically quite different from the validation of an immunoassay. Specifically, sections like "Number of experts used to establish ground truth", "Adjudication method", "Multi-Reader Multi-Case (MRMC) comparative effectiveness study", and "Effect size of how much human readers improve with AI vs without AI assistance" are relevant to AI/ML device validation studies, not typically to immunoassay validation.

An immunoassay like the Access OV Monitor is validated by demonstrating its analytical performance characteristics (e.g., precision, linearity, limits of detection) and method comparison against a predicate device, rather than by human reader studies or expert consensus on images.

Therefore, many of the requested fields are not applicable to this type of device and the information provided in the document. However, I will do my best to extract the relevant information where it exists and explicitly state when a requested criteria is not applicable.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary for the Access OV Monitor assay:

Device: Access OV Monitor Immunoassay

The study primarily focuses on demonstrating the substantial equivalence of the new Access OV Monitor assay run on the Dxl 9000 Access Immunoassay Analyzer to its predicate device (Access OV Monitor assay on the Access Immunoassay System, K023597). This is achieved by comparing their analytical performance characteristics.

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state "acceptance criteria" in a tabulated format for each performance metric, but rather lists the study results and implies they met predefined criteria (e.g., "met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.09"). The "acceptance criteria" column below is inferred from these statements and typical IVD validation expectations.

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

• Method Comparison Study: 152 samples.
• Imprecision Study: 120 replicates per sample level (e.g., Sample 1, Sample 2, etc, see N column in table). "Multiple samples" tested in triplicate in 2 runs per day for a minimum of 20 days.
• Data Provenance: The document does not specify the country of origin of the data or whether samples were retrospective or prospective. It is typical for immunoassay validation studies to use a mix of clinical samples (retrospective) and spiked samples.

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

• Not Applicable. This is an immunoassay, not an AI/ML diagnostic imaging device. The "ground truth" for the performance characteristics of an immunoassay is its analytical measurements, often compared against a reference method or validated predicate, not expert consensus on images.

4. Adjudication Method for the Test Set

• Not Applicable. See point 3.

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 an immunoassay, not an AI/ML diagnostic imaging device intended to assist human readers.

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

• Not Applicable. This is an immunoassay, the "performance" is the analytical output of the instrument-reagent system itself, which is inherently "standalone" in generating the quantitative result. There's no separate "algorithm" performance in the sense of an AI model.

7. The Type of Ground Truth Used

For an immunoassay, "ground truth" refers to the true concentration of the analyte, which is established through:

• Reference Methods: Highly accurate and precise methods not explicitly detailed but implied by standard validation practices.
• Comparative Measurements against a Predicate Device: The current study uses the predicate device (Access OV Monitor on the Access Immunoassay System) as its primary comparator to establish substantial equivalence.
• Known Concentrations: For linearity and limits studies, samples are often prepared at known concentrations (e.g., by diluting a high-concentration sample).

8. The Sample Size for the Training Set

• Not Applicable. This is an immunoassay, not an AI/ML device that requires a "training set" in the machine learning sense. The assay is "trained" or developed through biological and chemical methods, and its performance is characterized through analytical validation.

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

• Not Applicable. See point 8.

Ask a specific question about this device

For in vitro diagnostic use with the IMMULITE® 1000 Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second look procedures.

For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of CA125 antigen in serum, as an aid in monitoring the response to therapy for patients with epithelian ovarian cancer, and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

The IMMULITE®/IMMULITE 1000 OM-MA Assay is comprised of OM-MA Test Units (beads coated with murine monoclonal anti-CA125 antibody), OM-MA Cycle 1 Reagent Wedge (alkaline phosphatase conjugated to rabbit polyclonal anti-CA125 antibody in buffer), OM-MA Cycle 2 Reagent Wedge (buffer), and OM-MA Adjustors (Low and High, CA125 in a nonhuman protein/buffer matrix).

The IMMULITE® 2000 OM-MA Assay is a newer generation instrument that dispenses an individual bead from a pack into a separate reaction tube. It is comprised of OM-MA Bead Pack (beads coated with murine monoclonal anti-CA125 antibody), OM-MA Reagent Wedge (Well 1: alkaline phosphatase conjugated to rabbit polyclonal anti-CA125 antibody in buffer; Well 2: buffer), and OM-MA Adjustors (Low and High, CA125 in a nonhuman protein/buffer matrix).

Both assays are solid-phase, two-site chemiluminescent immunometric assays that measure CA125 antigen quantitatively in serum.

The Siemens Healthcare Diagnostics Products Ltd IMMULITE/IMMULITE 1000 OM-MA and IMMULITE 2000 OM-MA assays are intended for the quantitative measurement of CA125 antigen in serum. The devices aid in monitoring the response to therapy for patients with epithelial ovarian cancer and in detecting residual ovarian cancer in patients who have undergone first-line therapy.

Here's an analysis of the acceptance criteria and study proving device meets these criteria:

1. Table of Acceptance Criteria and Reported Device Performance

For IMMULITE/IMMULITE 1000 OM-MA Assay (modified):

For IMMULITE 2000 OM-MA Assay (modified):

2. Sample Size and Data Provenance

• Method Comparison Test Set: A total of 253 patient samples were used for method comparison studies for both the IMMULITE 1000 and IMMULITE 2000 assays. The documentation does not specify the country of origin of the data or whether it was retrospective or prospective.
• Precision Test Set: Five serum samples were tested for each assay (IMMULITE 1000 and IMMULITE 2000). The samples were tested in duplicate over 20 days, two runs per day, for a total of 80 replicates per sample level.
• Reproducibility Test Set: Five serum samples were tested for each assay (IMMULITE 1000 and IMMULITE 2000) using a 5x5x3 experimental design (5 days, 5 replicates, 3 reagent lots).
• Recovery Test Set: 19 samples were used for spike and recovery studies.
• Reference Range Verification Test Set: For each assay (IMMULITE 1000 and IMMULITE 2000), "apparently healthy female samples" were used. Specifically, for IMMULITE 1000, n=50 for Lot 1 and Lot 2, and n=45 for Lot 3. For IMMULITE 2000, n=50 for all three lots. The provenance is not explicitly stated beyond "healthy female samples."
• Stability Test Set: Native patient samples were used for accelerated stability studies, but the exact number of unique samples is not specified.

3. Number of Experts and Qualifications for Ground Truth

This device is an in vitro diagnostic (IVD) assay for quantitative measurement of a biomarker (CA125). The performance claims are based on analytical performance characteristics, not on interpretation of images or clinical outcomes by experts in the typical sense of a diagnostic imaging AI device. Therefore, the concept of "experts" to establish a ground truth for a test set, like radiologists or pathologists, is not directly applicable here. The "ground truth" for analytical performance studies is established by the assay's ability to accurately and precisely measure the analyte concentrations.

4. Adjudication Method for the Test Set

Not applicable. As an IVD assay measuring an analyte concentration, there is no adjudication process similar to that for subjective diagnostic interpretations. Performance is assessed through statistical analysis of quantitative results against established analytical methods and specifications.

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

No. An MRMC study is relevant for diagnostic imaging devices where multiple human readers interpret cases. This document describes an in vitro diagnostic assay that quantitatively measures a biomarker, not a device requiring human interpretation for diagnosis. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply.

6. Standalone Performance Measurement

Yes, the studies described are essentially standalone performance studies of the IMMULITE/IMMULITE 1000 OM-MA and IMMULITE 2000 OM-MA assays. The device (the assay) itself generates the quantitative measurement. The "human-in-the-loop" aspect, for this type of device, would be the clinician interpreting the numerical results in the context of a patient's treatment and disease status, a step downstream from the device's analytical performance. The studies focus on the analytical accuracy, precision, linearity, and interference of the assay itself.

7. Type of Ground Truth Used

The ground truth used for these analytical studies is primarily:

• Quantitative Reference Values / Expected Values:
  • For Detection Limits (LoB, LoD, LoQ), ground truth is based on the statistical determination of the lowest measurable concentrations.
  • For Linearity, ground truth is established by preparing samples with known, serially diluted concentrations (expected values).
  • For Method Comparison, the predicate device's results are used as the comparative "ground truth" (or reference method) to assess equivalence.
  • For Precision and Reproducibility, the ground truth is the inherent variability of the measurements around a mean dose.
  • For Spike Recovery, ground truth is the "expected" concentration after spiking known amounts of analyte into samples.
  • For Specificity (Cross-reactivity), ground truth is the known concentration of potentially cross-reacting substances.
  • For Interference, ground truth is the known concentration of potentially interfering substances.
  • For Reference Range, ground truth is derived from the established reference interval for healthy individuals (≤ 21 U/mL).

8. Sample Size for the Training Set

This document does not specify a separate "training set" or its size in the context of artificial intelligence or machine learning. The studies described are analytical performance validations for an in vitro diagnostic assay, which typically involve testing samples to verify performance against pre-defined specifications rather than training a machine learning model.

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

As there is no mention of a "training set" in the context of AI/ML for this device, information on how its ground truth was established is not provided or applicable. The ground truth for the performance validation studies, as described in point 7, is based on established analytical methods and known concentrations.

Ask a specific question about this device

For the quantitative measurement of OC 125 defined antigen concentration in human serum and plasma (EDTA or heparin) using the VITROS 5600 Integrated System. The VITROS CA 125 II assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

The VITROS Immunodiagnostic Products CA 125 II Reagent Pack (test) is performed using the VITROS CA 125 II Reagent Pack and VITROS CA 125 II Calibrators on the VITROS 5600 System. An immunometric immunoassay technique is used, which involves the reaction of OC 125 present in the sample with a microwell coated with biotinylated Antibody (Mouse monoclonal anti-OC 125) bound to Streptavidin, and a Horseradish Peroxidase (HRP)-labelled antibody conjugate (Mouse monoclonal anti- OC 125). Unbound (HRP)-labeled anti-OC 125 antibody conjugate is removed by washing. The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of conjugate bound is directly proportional to the concentration of OC 125 present in the sample.

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the VITROS Immunodiagnostic Products CA 125 II Reagent Pack:

This document is a 510(k) summary for a medical device ([K221355](https://510k.innolitics.com/search/K221355)) and primarily focuses on demonstrating substantial equivalence to a predicate device. As such, it reports on various analytical performance studies rather than user studies or comparative effectiveness studies involving human readers or AI.

Acceptance Criteria and Reported Device Performance

Ask a specific question about this device

For in vitro diagnostic use in the quantitative, serial determination of CA 125 in human serum and plasma (EDTA and lithium heparin) and to aid in the management of patients with ovarian carcinoma using the ADVIA Centaur® XP and ADVIA Centaur® XPT systems. The test is intended for use as an aid in monitoring patients previously treated for ovarian cancer. Serial testing for CA 125 in the serum and plasma of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of ovarian cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment. It is recommended that the ADVIA Centaur CA 125II assay be used under the order of a physician trained in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

The ADVIA Centaur CA 125II assay is comprised of the following reagents: CA 125II Lite Reagent (monoclonal mouse anti-M11 antibody labeled with acridinium ester and monoclonal mouse anti-OC 125 labeled with fluorescein in phosphate buffer with bovine serum albumin and preservatives) and CA 125II Solid Phase Reagent (monoclonal mouse anti-fluorescein antibody coupled to paramagnetic particles in phosphate buffer with bovine serum albumin and preservatives).

Here's an analysis of the provided text regarding the acceptance criteria and study for the ADVIA Centaur CA 125II assay.

Acceptance Criteria and Device Performance for ADVIA Centaur CA 125II Assay

The Siemens Healthcare Diagnostics Inc. ADVIA Centaur CA 125II Assay is an in vitro diagnostic device for the quantitative, serial determination of CA 125 in human serum and plasma (EDTA and lithium heparin) to aid in the management of patients with ovarian carcinoma. The submission K200199 primarily focused on adding plasma as an accepted sample type.

Table of Acceptance Criteria and Reported Device Performance

Study Details:

1. Sample size used for the test set and the data provenance:

   • Method Comparison: 224 samples (range 3.1 to 466.6 U/mL). Data provenance is not explicitly stated (country, retrospective/prospective).
   • Specimen Equivalence:
     • Dipotassium EDTA plasma vs. Serum: 162 sample pairs.
     • Lithium Heparin plasma vs. Serum: 119 sample pairs.
     • Data provenance is not explicitly stated (country, retrospective/prospective).
   • Interferences: 2 tested analyte concentration levels for each substance (EDTA and Heparin) with "Analyte Concentration" values given. Sample size per level is not specified, but typically multiple replicates are used. Data provenance is not explicitly stated.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
   This device is an in vitro diagnostic (IVD) assay for measuring CA 125 levels. The "ground truth" for this type of device is typically established by reference methods or predicate devices (as seen in the method comparison and specimen equivalence studies), not by expert consensus on image interpretation or clinical diagnosis. Therefore, this question is not directly applicable in the context of this IVD device. The validation relies on the quantitative measurement accuracy against established methods.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
   Not applicable, as this is an IVD assay measuring an analyte, not requiring human adjudication of results in the way image interpretation or clinical diagnosis would.

4. 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 an IVD laboratory assay, not an AI-powered diagnostic imaging or clinical decision support system involving human readers.

5. If a standalone (i.e., algorithm only without human-in-the loop performance) was done:
   Yes, the performance characteristics (detection limits, method comparison, specimen equivalence, interferences) represent the standalone performance of the ADVIA Centaur CA 125II assay. It's a fully automated immunoassay, so its performance is inherently "algorithm only" (the biochemical reaction and detection system). While results are used by clinicians, the measurement itself is standalone.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
   For method comparison, the "ground truth" was established by the Bayer Immuno 1® CA 125II assay, which served as the reference method. For specimen equivalence, human serum served as the reference matrix against which plasma samples were compared. For detection limits, it's based on statistical analysis of blank and low-concentration samples.

7. The sample size for the training set:
   Not applicable in the AI sense. This is a traditional immunoassay, not a machine learning model that requires a "training set." The assay principle, design, and reagent formulation were established through standard laboratory development and validation processes, not machine learning training.

8. How the ground truth for the training set was established:
   Not applicable for the reason stated above. The "ground truth" for developing and calibrating an immunoassay involves extensive analytical chemistry, antibody development, and optimization of reaction conditions, with reference to known standards and established methods, rather than a "training set" with established ground truth labels in the machine learning context.

Summary of the Study that Proves the Device Meets Acceptance Criteria:

The study detailed in the 510(k) submission K200199 focused on demonstrating the substantial equivalence of the ADVIA Centaur CA 125II assay with the expanded sample type (EDTA and lithium heparin plasma) to its predicate device, which only accepted serum.

The key studies presented to support this included:

• Detection Limit determination: Performed in accordance with CLSI Document EP17-A2, establishing LoB, LoD, and LoQ. These values were provided and indicate the analytical sensitivity of the assay.
• Method Comparison: The assay's performance was compared against the Bayer Immuno 1® CA 125II assay using 224 samples. A strong correlation (r = 0.992) and a regression equation (ADVIA Centaur CA 125II = 1.025 (Bayer Immuno 1) + 1.15 U/mL) were reported, demonstrating agreement with a commonly used predicate.
• Specimen Equivalence: This crucial study, performed in accordance with CLSI Document EP09-A3, compared results from EDTA plasma and lithium heparin plasma against serum samples. The reported slopes (0.95 for EDTA, 1.03 for lithium heparin) and intercepts (-0.4 U/mL for EDTA, -0.2 U/mL for lithium heparin) with corresponding 95% confidence intervals falling close to the ideal (slope=1, intercept=0) and high correlation coefficients (1.00 for both) indicate that plasma matrices yield comparable results to serum. This directly supports the safety and effectiveness of using plasma samples.
• Interference testing: Performed per CLSI Document EP07-ed3, demonstrating that high concentrations of EDTA and Heparin do not significantly interfere with the assay's results (bias within low single digits).

The submission argues that "The assay principle, design and reagent formulation has not changed from the original device, therefore, the analytical performance studies and data previously reviewed under 510(K) K020828 continues to apply to this assay." The additional studies specifically addressed the change in sample type (plasma), showing that the device performs equivalently with these new sample types as it does with serum, thus meeting the requirements for substantial equivalence.

Ask a specific question about this device

Elecsys CA 125 II is an immunoassay for the in vitro quantitative determination of OC 125 reactive determinants in human serum, Li heparin, K2-EDTA, as well as Li-heparin plasma tubes containing separating gel on the cobas e 411 analyzer.

These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer (excluding those with cancer of low malignant potential).

This immunoassay is indicated for use as an aid in the detection of recurrent ovarian carcinoma. This immunoassay is further indicated for use in monitoring patients for disease progress or response to therapy.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 411 immunoassay analyzers.

For use in the verification of the callbration established by the Elecsys CA 125 II reagent on the Elecsys and cobas e immunoassay analyzers.

The CA 125 II assay employs a sandwich test principle using biotinylated monoclonal CA 125-specific antibody and a monoclonal CA 125-specific antibody labeled with a ruthenium complex to form a sandwich complex. The use of streptavidin-coated microparticles serves as the solid phase for the electrochemiluminescence detection.

Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code.

The CA 125 II application is identical to the predicate assay (K972162). This submission is being done to modernize the labeling by adding the LoB, LoD and LoQ data and to change the sample:reagent ratio from 40:60μL to 20:70μL. Additionally, based on internal stability data the calibration frequency has been extended from 4 to 8 weeks.

The Elecsys CA 125 II CalCheck is a lyophilized product consisting of equine serum in level 1 and human serum matrix for levels 2 and 3. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.

Here's a breakdown of the acceptance criteria and the study details for the Elecsys CA 125 II Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document provides a comparison table (Table 1) between the predicate device (Elecsys CA 125 II, K972162) and the candidate device (Elecsys CA 125 II Assay), highlighting both similarities and differences, including labeled performance characteristics. Since explicit "acceptance criteria" are not given in a numerical form that can be directly compared to "reported performance" for each item, I will present the key performance characteristics detailed for the candidate device as its reported performance, implicitly indicating what was demonstrated to FDA for substantial equivalence.

Ask a specific question about this device

Lumipulse G CA125II Immunoreaction Cartridges For in vitro diagnostic use. Lumipulse G CA125II is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of CA125 in human serum and plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System. The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with ovarian cancer. Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. Lumipulse G CA125II Calibrators Lumipulse G CA125II Calibrators are for use in the calibration of the LUMIPULSE G System for the quantitative measurement of CA125 in human serum or plasma (sodium heparin, or dipotassium EDTA). LUMIPULSE G1200 System LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation and photometric measurement.

Lumipulse G CA125Il is an assay system, including a set of immunoassay reagents, for the quantitative measurement of CA125 in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G System. Lumipulse G CA125II Immunoreaction Cartridges consists of 3 x 14 tests. Each kit contains Antibody-Coated Particle Solution and Enzyme-Labeled Antibody Solution. Lumipulse G CA125II Calibrators Each calibrator kit contains one bottle each of Calibrators 1 and 2. The calibrator kit is packaged separately. LUMIPULSE G1200 System LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation, and photometric measurement. The chemiluminescent enzvme immunoassay system is carried out using the ferrite particle coated with antigen or antibody and conjugate with alkaline phosphatase and the chemical luminescent substrate. The luminescence which is produced by the chemiluminescent enzyme immunoassay is measured by photometric detector.

The provided text describes the Lumipulse G CA125II Immunoreaction Cartridges, Lumipulse G CA125II Calibrators, and LUMIPULSE G1200 System, which are used for the quantitative determination of CA125 in human serum and plasma to aid in monitoring recurrence or progressive disease in patients with ovarian cancer.

Here's an analysis of the acceptance criteria and study data provided:

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

Unfortunately, the document does not explicitly state pre-defined "acceptance criteria" in a structured table. However, performance goals can be inferred from the study results and general clinical practice for such assays. The study's conclusion states that the assay "is substantially equivalent to the performance of the Siemens ADVIA Centaur CA 125II assay," implying that meeting the performance of the predicate device serves as an acceptance criterion.

Based on the provided performance characteristics, here's a reconstructed table with inferred performance goals and reported performance:

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

• Precision/Reproducibility (Within-laboratory): 8 human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day for 20 days (n=80 for each sample).
• Precision (Site-to-site): Human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day at each of 3 external laboratory sites for 10 days (n=40 for each sample). The document does not specify the country of origin or whether the data was retrospective or prospective.
• Precision (Lot-to-lot): Human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day for each of 3 lots for 10 days (n=40 for each sample).
• Linearity/Assay Reportable Range: One human serum specimen pool and one K2 EDTA plasma specimen pool with high CA125 levels were diluted with low CA125 levels. Specific N for individual samples is not given, but the study method is described.
• Recovery: Not specified, but involved human serum and K2 EDTA plasma samples.
• Limit of Detection (LoD): Seven low-level specimens were tested over 3 days using two LUMIPULSE G1200 Systems and two Lumipulse G CA125II lots, resulting in 120 determinations for each panel.
• Analytical Specificity (Interference): Human serum and K2 EDTA plasma specimen pools supplemented with potentially interfering compounds.
• Method Comparison:
  • 102 samples (range 15.5-822.2 U/mL) for direct comparison.
  • 120 samples (range 15.5-1128.8 U/mL) including those requiring dilution.
    The document does not specify the country of origin or whether the data was retrospective or prospective for these samples.
• Matrix Comparison: Not specified, but involved different tube types (SST, K2EDTA, Lithium Heparin, and Sodium Heparin) versus red top serum samples.
• Clinical Studies (Monitoring of Disease Status): 59 patients, with a total of 289 pairs of observations (average of 5.9 observations per patient). The data provenance (country, retrospective/prospective) is not specified.
• Expected values/Reference range:
  • Healthy premenopausal women: N=120
  • Healthy postmenopausal women: N=120
  • Benign Gynecological Disease: N=260
  • Other Benign Disease: N=40
  • Congestive Heart Failure: N=40
  • Hypertension: N=40
  • Pregnant: N=40
  • Ovarian Cancer: N=105
  • Bladder Cancer: N=40
  • Breast Cancer: N=40
  • Endometrial Cancer: N=40
  • GI Cancer: N=40
  • Lung Cancer: N=40
    The data provenance (country, retrospective/prospective) is not 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)

For the "Monitoring of Disease Status in Patients Diagnosed with Ovarian Cancer" study, the ground truth ("disease progression") was determined by comparing "changes in CA125 levels in serial serum samples from 59 patients compared to changes in disease status." The document states that "Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer." However, it does not specify the number of experts or their qualifications who established the "disease status" ground truth (i.e., whether the disease had progressed or not, independently of the CA125 reading).

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

The document does not describe an adjudication method for establishing the ground truth for the clinical study. It implies that "disease status" was determined by "other clinical methods," but how conflicts or uncertainties in those methods were resolved is not detailed.

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 conducted. This device is an automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers interpreting results. Its purpose is to quantify CA125 levels, and the clinical study evaluates its performance in monitoring disease status based on changes in these quantitative values, not reader performance.

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

Yes, the studies presented are effectively standalone performance evaluations of the Lumipulse G CA125II assay and the LUMIPULSE G1200 System. The precision, linearity, recovery, detection limits, analytical specificity, and method comparison studies evaluate the algorithm's (the assay's) performance in quantifying CA125 levels. The clinical monitoring study also evaluates the assay's ability to track disease status based on its quantitative output, independent of human interpretive reading of images or complex data (beyond simple interpretation of CA125 value changes).

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

For the clinical monitoring study, the ground truth for "disease progression" was based on "changes in disease status," which is referred to as being determined by "other clinical methods used for monitoring ovarian cancer." This suggests a composite clinical ground truth, likely involving a combination of imaging, clinical assessment, and potentially other biomarkers or pathology, but the specific details are not provided. It is not explicitly stated as pathology or expert consensus, but rather a broader "clinical methods."

8. The sample size for the training set

The document does not describe a "training set" in the context of machine learning. The studies described are performance validation studies for an in vitro diagnostic device, which typically involves analytical validation and clinical validation using a distinct set of samples. The assay itself is a Chemiluminescent Enzyme Immunoassay (CLEIA), a biochemical measurement system, not a machine learning algorithm that requires a separate training set.

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

As there is no "training set" for a machine learning algorithm, this question is not applicable to the provided document. The ground truth for the reference calibrators for the assay itself is established via traceability to "Fujirebio Diagnostics maintained reference preparation" and correlation to "Fujirebio Diagnostics' CA125II RIA."

Ask a specific question about this device

The LOCI CA 125 II™ method is an in vitro diagnostic test for the quantitative measurement of CA 125 antigen in human serum and lithium heparin and EDTA plasma on the Dimension Vista® System. Measurements of CA 125 are used as an aid in monitoring disease progress or response to therapy or for the recurrent or residual disease for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. It is recommended that the LOCI CA 125 Il method be used in conjunction with signs and symptoms of a clinical evaluation by a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

The LOCI 6 CAL is an in vitro diagnostic product for the calibration of Alpha-Fetoprotein (AFP), Carcinocmbryonic Antigen (CEA), and CA 125 (CA125) methods on the Dimension Vista® System.

The LOCI CA 125Il™ method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated anti-CA 125 monoclonal antibody (M11) fragment. The first bead reagent (Chemibeads) is coated with an anti-CA125 monoclonal antibody (OC 125) and contains a chemiluminescent dye. The use of the M11 antibody in combination with OC 125 defines this method as a second generation CA 125 assay. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-CA 125-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the CA 125 concentration in the sample.

The LOCI 6 calibrator is a multi-analyte liquid, frozen bovine serum albumin based product containing Alpha-Fetoprotein from human cord blood, Carcinoembryonic Antigen from human cell culture and CA 125 from human cell culture. The kit consists of ten vials per level (A-E), 2.0 mL per vial. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.

Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension Vista® LOCI CA 125 (CA125) Flex® Reagent Cartridge, structured according to your request:

Based on the provided 510(k) Summary of Safety and Effectiveness, this document describes an in vitro diagnostic (IVD) device meant to quantify a biomarker (CA 125) rather than a device for image analysis or other AI-based diagnostics. Therefore, many of the requested fields (like "Number of experts used to establish the ground truth for the test set," "Adjudication method," "MRMC comparative effectiveness study," and details about AI performance) are not applicable to this type of device and submission.

The "acceptance criteria" for an IVD like this are typically demonstrated through various performance characteristics, often compared to a predicate device. The "study that proves the device meets the acceptance criteria" refers to a battery of analytical performance studies (e.g., precision, accuracy/method comparison, linearity, interference, limit of detection) rather than a clinical reader study typical for imaging AI.

1. Table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a table form with numerical targets, which is common for full submission documents but often summarized for the 510(k) summary. Instead, it states that "Comparative testing described in the submission report demonstrates substantial equivalent performance." This implies that the performance of the new device (LOCI CA 125II™ Flex® Reagent) was found to be statistically comparable to the predicate device (ADVIA Centaur CA125II assay) across various analytical parameters. The key comparison points highlighted in the document focus on feature similarities for substantial equivalence, not performance metrics.

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

The document does not detail specific sample sizes for "test sets" in the way an AI study would. For IVD devices, "test set" data usually refers to samples used in analytical performance studies (e.g., precision, linearity, method comparison).

• Sample Size: Not explicitly stated in the summary for individual analytical studies. Such details would typically be found in the full submission report's study protocols and results sections.
• Data Provenance: Not specified in the summary. For IVD analytical studies, samples often come from clinical laboratories or biobanks, and the country of origin is not always highlighted unless there's a specific regulatory or demographic reason. The studies are prospective in the sense that they are conducted specifically to validate the device's performance, but the samples themselves might be retrospective collections.

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

Not Applicable (N/A): This is an in vitro diagnostic assay for measuring a biomarker concentration, not an imaging or AI diagnostic device requiring expert interpretation for ground truth. The "ground truth" for an IVD refers to the true concentration of the analyte, often established by reference methods or gravimetric preparation of controls/calibrators.

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

Not Applicable (N/A): Adjudication methods are relevant for human interpretation of data, typically in clinical trials or expert consensus for image labeling. This is an automated analytical device.

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 (N/A): This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool. No human readers are involved in the direct output of this device.

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

Yes, in essence. The performance described for the LOCI CA 125II™ method is inherently "standalone" in that it's the direct analytical output of the instrument and reagents, quantifying CA 125 in a sample without human intervention in the measurement process itself. The "algorithm" here is the chemical reaction and light detection process. The summary implies the performance was evaluated on this basis.

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

For an IVD assay measuring a biomarker concentration (CA 125), the "ground truth" for analytical studies would typically be:

• Reference Methods: For accuracy and method comparison, samples might be run on established, validated reference methods, or the predicate device itself serves as the comparator.
• Known Concentrations: For linearity, limit of detection, and calibration, samples are often prepared with known, certified concentrations of the analyte (e.g., using purified CA 125 antigen).
• Definitive Quantitation: In some cases, highly accurate quantitative techniques (e.g., mass spectrometry, although less common for routine biomarkers) might be considered a gold standard.

(The document does not explicitly state which ground truth method was used but it would be one of the above for an IVD.)

8. The sample size for the training set

Not Applicable (N/A): This is an in vitro diagnostic assay that is not based on machine learning or AI models requiring "training sets" in the traditional sense. The development of such assays involves reagent formulation, instrument design, and extensive analytical validation, but not machine learning training.

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

Not Applicable (N/A): As there is no "training set" in the context of machine learning for this IVD, no ground truth was established in that manner. The "ground truth" established during the development and validation phase would be related to the chemical and physical properties of the reagents and the detection system, as described in point 7.

Ask a specific question about this device

VIDAS® CA 15-3 is an automated quantitative test for use on the VIDAS instruments for the quantitative measurement of CA 15-3 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 15-3 is indicated for the serial measurement of CA 15-3 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with breast cancer for disease progression or response to therapy in conjunction with other clinical methods. The VIDAS CA 15-3 assay can also be used as an aid in the detection of recurrence in previously treated Stage II and III breast cancer patients.

VIDAS CA 15-3 is an automated quantitative test for use on the VIDAS instruments for the quantitative measurement of CA 15-3 levels in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 15-3 assay is indicated for the serial measurement of CA 15-3 as an aid in the monitoring of disease progression or response to therapy in patients previously diagnosed with breast cancer.

The assay principle combines a two-step immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. It is coated with mouse monoclonal 115D8 antibodies. The other assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs).

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. This operation enables the monoclonal 115D8 antibody fixed onto the interior wall of the SPR to capture the reactive antigenic determinants present in the sample. Unbound components are eliminated during the washing steps. Alkaline phosphatase labeled monoclonal DF3 antibody (conjugate) is then incubated in the SPR where it binds with the CA 15-3 reactive antigenic determinant. Unbound conjugate is then eliminated during the washing steps.

During the final detection step, the substrate (4-Methyl-umbellifery| phosphate) is cycled in and out of the SPR. The conjuqate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methy)-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of CA 15-3 reactive antigenic determinants present in the sample.

At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory, and then printed out.

Here's a summary of the acceptance criteria and study details for the VIDAS® CA 15-3 Assay, based on the provided text:

Acceptance Criteria and Device Performance for VIDAS® CA 15-3 Assay

The device acceptance was based on demonstrating substantial equivalence to a predicate device (TOSOH ST AIA-PACK BRCA) through performance data, including analytical and clinical comparisons. The summary does not explicitly state acceptance criteria in terms of target values for slope or intercept; rather, it presents the results of the comparison to support substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance:

Ask a specific question about this device

VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of OC 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with Stage IV (metastatic) ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 II assay can also be used as an aid in the early detection of recurrence in previously treated Stage II and III ovarian cancer patients.

VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of CA 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with Stage IV (metastatic) ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 II assay can also be used as an aid in the early detection of recurrence in previously treated Stage II and III ovarian cancer patients.

CA 125 II is a registered trademark from Fujirebio Diagnostics Inc. (formerly named Centocor Diagnostics of Pennsylvania, Inc.)

The assay principle combines a two-step immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. It is coated with mouse monoclonal M 11 antibodies. The other assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. This operation enables the monoclonal M11 antibody fixed onto the interior wall of the SPR to capture the reactive antigenic determinants present in the sample. Unbound components are eliminated during the washing steps. Alkaline phosphatase labeled mouse monoclonal OC 125 antibody (conjugate) is then incubated in the SPR where it binds with the OC 125 reactive antigenic determinant. Unbound conjugate is then eliminated during the washing steps.

During the final detection step, the substrate (4-Methyl-umbelliferyl phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of OC 125 reactive antigenic determinants present in the sample.

At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory, and then printed out.

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

Acceptance Criteria and Device Performance for VIDAS® CA 125 II Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document describes performance characteristics rather than explicit "acceptance criteria" with pass/fail thresholds. However, we can infer the tested performance against predicate device or established analytical goals.

• Between-site CV: 4.15%
• Between-lot CV: 1.01%
• Between-recalibration CV: 1.87%
• Between-day CV: 0.00%
• Between-run CV: 0.99%
• Within-run CV: 3.40%
• Total CV: 5.85%

Pool B (75.3 U/mL):

• Between-site CV: 2.13%
• Between-lot CV: 0.00%
• Between-recalibration CV: 2.26%
• Between-day CV: 1.08%
• Between-run CV: 2.00%
• Within-run CV: 3.50%
• Total CV: 5.20%

Pool C (18.9 U/mL):

• Between-site CV: 2.43%
• Between-lot CV: 0.79%
• Between-recalibration CV: 1.96%
• Between-day CV: 0.74%
• Between-run CV: 1.79%
• Within-run CV: 3.35%
• Total CV: 5.03% |
  | Measurement Range | Clearly defined and clinically relevant. | 4.00 - 600.00 U/mL |
  | Analytical Detection Limit (LoB/LoQ) | Below the lower limit of the measurement range. | Estimated to be less than 4 U/mL. |
  | Hook Effect | No significant hook effect at high concentrations. | No hook effect found up to 200,000 U/mL. |
  | Method Comparison (vs. Predicate) | Strong correlation and agreement with a legally marketed predicate device (TOSOH ST AIA Pack CA 125). Implicitly, the Deming regression parameters (slope, intercept, and their confidence intervals) and overall correlation should demonstrate substantial equivalence. | Comparison Study:
• N = 210 samples (including 77 ovarian cancer patients and 133 monitoring samples)
• Equation: Y = 0.93X - 58.10
• 95% Confidence Interval for Intercept: -169.15 to 52.95
• 95% Confidence Interval for Slope: 0.61 to 1.25
• Range of samples: VIDAS: 4.0 - 31801 U/mL; Predicate: 2.0 - 29940 U/mL
• Conclusion: The device is considered substantially equivalent to the predicate. |

2. Sample Size and Data Provenance for Test Set (Method Comparison)

• Sample Size: 210 samples. This includes 77 samples from women with ovarian cancer and 133 samples for monitoring disease status.
• Data Provenance: The document does not explicitly state the country of origin. It indicates the samples were serum samples from women with ovarian cancer. It implies a retrospective or a mixed prospective/retrospective design, as samples were "randomly chosen" from existing patient populations.

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

Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker. The "ground truth" for the method comparison study is the result obtained from the predicate device (TOSOH ST AIA Pack CA 125). There are no human experts involved in establishing a subjective ground truth for the CA 125 values.

4. Adjudication Method for Test Set

Not applicable. As described above, this is a quantitative measurement comparison, not a study requiring human expert adjudication of a subjective finding. The comparison is against the predicate device's quantitative results.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for imaging or other diagnostic tools where human readers interpret results, and the AI's effect on their performance is evaluated. The VIDAS® CA 125 II Assay is a fully automated quantitative immunoassay.

6. Standalone (Algorithm Only) Performance Study

Yes, the studies described (Precision, Measurement Range, Analytical Detection Limit, Hook Effect, and Comparison with other methods like the predicate device) represent the standalone performance of the VIDAS® CA 125 II Assay. It is an automated system without a human-in-the-loop for the quantification process itself.

7. Type of Ground Truth Used

• For Precision, Measurement Range, Analytical Detection Limit, Hook Effect: These are analytical performance characteristics where the "ground truth" is established through well-defined laboratory analytical methods and controls, ensuring intrinsic performance of the assay.
• For Method Comparison: The "ground truth" for comparison was the quantitative results obtained from the predicate device (TOSOH ST AIA Pack CA 125 Enzyme Immunoassay). The goal was to demonstrate substantial equivalence to an already legally marketed device.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning, as this is an immunoassay, not an AI/ML-based diagnostic algorithm. However, calibration curves are established for each kit lot and calibrator lot. The number of samples used to establish these master curves is not specified, but it's an internal process traced to working standards.

9. How the Ground Truth for the Training Set (Calibration) was Established

For the VIDAS® CA 125 II Assay, the equivalent of "ground truth" for its internal calibration (referred to as master curves and calibrator lots) is established by:

• Traceability to working standards established by bioMérieux, Inc.
• Value assignment by the Fujirebio Diagnostics, Inc. radioimmunoassay method.

This indicates a hierarchical system where internal standards are calibrated against a recognized reference method to ensure accuracy and consistency.

Ask a specific question about this device

Immulite 2500 OM-MA: For in vitro diagnostic use with the IMMULITE 2500 Analyzer- for the quantitative measurement of CA125 antigen in human serum, as an aid in monitoring the response to therapy for patients with epithelial ovarian cancer and in detecting residual ovarian cancer in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures.

Immulite Tumor Marker Controls: TMC is an assayed, serum-based, tri-level control containing analytes associated with malignancy which are commonly measured by immunoassay. It is intended strictly for in vitro use as an aid in monitoring the day-to-day performance of assays for these constituents.

The IMMULITE 2500 OM-MA Immunoassay is a solid-phase, two-site, chemiluminescent immunometric assay for use with the IMMULITE 2500 Automated Analyzer.

The provided text is a 510(k) summary for the IMMULITE® 2500 OM-MA Immunoassay. It describes the device's intended use and classification, and states that it has been found substantially equivalent to a predicate device (IMMULITE 2000 OM-MA Immunoassay).

However, the document does not contain information about acceptance criteria, detailed study results proving device performance against those criteria, sample sizes for test and training sets, data provenance, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance.

Therefore, I cannot fulfill your request for a table of acceptance criteria and reported device performance or other detailed study information, as this information is not present in the provided text.

Ask a specific question about this device