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The Copalis™ TORC Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutinationbased immunoassay for the qualitative detection of total antibodies (IgG and IgM) to Toxoplasma gondii, rubella and cytomegalovirus (CMV) in human serum using the CopalisTM One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to determine the patient's immune status for rubella and to determine the patient's immunological experience for Toxoplasma gondii and CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

The Copalis TORC Total Antibody Assay is based on the principle of antibodydependent particle aggregation as detected by measurement of changes in light scattering. Due to the unique measuring system, a sample can be tested for antibodies to Toxoplasma gondii, rubella and CMV using a single reagent and obtain results for the individual antibodies. Sized latex microparticles coated with inactivated Toxoplasma gondii, rubella and CMV antigens aggregate in the presence of antibodies to these infectious agents. After 10 minutes of agitation, the levels of aggregation are determined by discrimination of particle sizes and measurement of the number of reacted and unreacted particles as they flow past a detector. Reactivity is assessed by the level of aggregation per particle size relative to a cutoff value. The Copalis TORC Total Antibody Assay detects the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor proficiency.

Here's an analysis of the acceptance criteria and the study proving device performance, based on the provided text for the Copalis™ TORC Total Antibody Assay:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in the provided text. However, the "Performance Data" section outlines the evaluated metrics and their results, which implicitly serve as the achieved performance benchmarks.

Detailed Study Information:

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

   • Clinical Sample Testing: A total of 250 serum samples were tested.
   • POL Proficiency Study: A 14-member blinded proficiency panel was used. Each panel member was tested in triplicate (across three runs) by multiple operators.
   • Data Provenance: The clinical sample testing was conducted at Sienna Biotech laboratory. The POL Proficiency Study was conducted at 3 POL sites. The text does not specify the country of origin but implies a US context given the FDA submission. Both studies appear to be prospective as they were conducted to evaluate the performance of the new device.

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

   • Clinical Sample Testing: The ground truth for this study was established by comparing the Copalis TORC Total Antibody Assay to the corresponding Abbott IMx assays. These predicate devices are established assays, implying their results serve as the reference standard. The text does not specify the number or qualifications of experts involved in running the Abbott IMx assays or in interpreting their results for ground truth determination.
   • POL Proficiency Study: The "expected" results for the 14-member blinded proficiency panel were established by in-house testing on a comparator assay. Similar to the clinical sample testing, the text does not detail the number or qualifications of experts involved in establishing these "expected" results.

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

   • The provided text does not describe an explicit adjudication method for resolving discordant results in either the clinical sample testing or the POL proficiency study. The ground truth was primarily established by comparator assays.

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:

   • This document describes an immunoassay device, not an AI-powered diagnostic system. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this device. The POL study did involve multiple operators (human users) to assess reproducibility and proficiency, but it was not framed as an AI-assist study.

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

   • The Copalis TORC Total Antibody Assay is a laboratory-based immunoassay system, not an algorithm that operates independently. Its performance data (sensitivity, specificity, reproducibility) are inherently "standalone" in the sense that they represent the device's analytical performance on samples, rather than human interpretation of device output. The "human-in-the-loop" aspect comes from laboratory personnel operating the system, not interpreting images or complex data in a way that AI would assist.

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

   • The ground truth for both the clinical sample testing and the POL proficiency study was established by results from comparator assays (Abbott IMx assays for clinical, and an unspecified "comparator assay" for the POL study's "expected" results). This falls under the category of reference standard testing using established diagnostic methods.

7. The sample size for the training set:

   • The provided document does not mention a training set. This is expected as the Copalis TORC Total Antibody Assay is an immunoassay, not a machine learning model that requires explicit training data. Its development would involve chemical and biological optimization, not algorithmic training.

8. How the ground truth for the training set was established:

   • Since there is no mention of a training set or machine learning components, the concept of establishing ground truth for a training set is not applicable to this device.

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The Copalis™ TORC, Toxo, Rubella, and CMV Total Antibody Assays use Coupled Particle Light Scattering (Copalis) technology in microparticle agglutination-based immunoassays for the qualitative detection of total antibodies (IgG and IgM) to Toxoplasma gondii, rubella and/or cytomegalovirus (CMV) in human serum using the Copalis™ I Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of these assays on a single serum specimen are used to determine the patient's immune status for rubella and to determine the patient's immunological experience for Toxoplasma gondii and CMV. When evaluating properly paired sera, the results of these assays are used to demonstrate seroconversion as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results).

These assays has not been FDA cleared or approved for the screening of blood or plasma donors.

The assay will also be offered as separate microparticle immunoassays for the qualitative detection of total antibodies (IgG and IgM) to Toxoplasma gondii, rubella and cytomegalovirus (CMV) in human serum using the Copalis™ One Immunoassay System. The intended use of the individual assays will be specific to the individual antibodies detected but, other than that, will remain the same as the combination assay.

Coupled Particle Light Scattering (Copalis) technology provides a rapid method for the measurement of antibodies to specific viral or protozoal pathogens.

The Copalis™ TORC, Toxo, Rubella, and CMV Total Antibody Assays are based on the principle of antibody-dependent particle aggregation as detected by measurement of changes in light scattering. Due to the unique measuring system, a sample can be tested for antibodies to Toxoplasma gondii, rubella and CMV using a single TORC reagent and obtain results for the individual antibodies. Sized latex microparticles coated with inactivated Toxoplasma gondii, rubella and CMV antigens aggregate in the presence of antibodies to these infectious agents. After 10 minutes of agitation, the levels of aggregation are determined by discrimination of particle sizes (for the TORC assay) and measurement of the number of reacted and unreacted particles as they flow past a detector. Reactivity is assessed by the level of aggregation per particle size relative to a cutoff value. The Copalis TORC and individual Total Antibody Assays detect the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor system performance.

Here's a breakdown of the acceptance criteria and study information for the Copalis TORC Total Antibody Assay, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the results presented in the clinical trials, specifically the "Relative Sensitivity" and "Relative Specificity" (which are effectively measures of accuracy against comparator devices). The reproducibility data also indicates levels of acceptable variation.

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

• Test Set Sample Size: A total of 769 serum samples were tested.
• Data Provenance: The samples were collected as part of clinical trials conducted at 3 sites (2 clinical laboratories and Sienna Biotech laboratory). The text states "20% of which were fresh samples," implying the remaining 80% were retrospective or banked samples. The country of origin is not explicitly stated, but given "Sienna Biotech, Inc." in Columbia, MD, it is likely the US. The nature of the samples being "patient specimens" suggests they were from individual patients.

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

The ground truth was established by comparison to predicate devices: the BioWhittaker ToxoStat, Becton Dickinson And Co. Rubascan, and CMVscan assays. Therefore, the "experts" were the established predicate assays themselves, which are assumed to have undergone prior rigorous validation. The qualifications of a human expert are not relevant here, as the comparison is device-to-device.

4. Adjudication Method for the Test Set

The adjudication method is described as "Agreement Following Resolution of Discordants." This indicates that samples where the Copalis assay results disagreed with the predicate assay results were further investigated or adjudicated to determine the true status, likely using a "tie-breaker" or a more definitive method. The exact method of resolution is not detailed (e.g., if a third, more definitive test was used, or if human review was involved).

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 study is an in vitro diagnostic (IVD) device, and its performance is evaluated objectively against established methods (predicate devices) on biological samples. There is no human reader "improving with AI vs. without AI assistance" in this context.

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

Yes, the performance reported is inherently standalone. The Copalis™ Immunoassay System is described as using "Coupled Particle Light Scattering (Copalis) technology" and "measurement of changes in light scattering" to detect aggregation and discrimination of particle sizes. The results are "assessed by the level of aggregation per particle size relative to a cutoff value." This indicates an automated system producing qualitative (positive/negative) results directly, without human interpretation of raw data for diagnosis.

7. The Type of Ground Truth Used

The primary type of ground truth used was the results from established, commercially available predicate devices (BioWhittaker ToxoStat, Becton Dickinson And Co. Rubascan, CMVscan assays). For the CDC serum panels, the ground truth was the known, characterized status of the samples as determined by the CDC. For reproducibility and reference standard testing, the ground truth was related to expected values and consistency, rather than a diagnostic 'truth' for patient samples.

8. The Sample Size for the Training Set

The text does not provide information on a specific training set size. As an immunoassay system, it likely relies on a pre-defined algorithm and cutoff values established during previous assay development and validation, rather than a "training set" in the machine learning sense. The clinical trials described here are for validation and performance assessment rather than training.

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

Since there is no explicit mention of a "training set" in the context of machine learning, the question of how its ground truth was established is not directly applicable. For a traditional immunoassay, the "training" (or development) phase involves establishing optimal reagent concentrations, reaction conditions, and cutoff values using a characterized set of positive and negative samples, which would have their true status determined by well-established diagnostic methods (e.g., other validated assays, clinical diagnosis, or a combination).

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The CopalisTM CMV Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutinationbased immunoassay for the qualitative and semi-quantitative detection of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum using the CopalisTM One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to indicate presence of antibody to CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion or a significant increase in antibody level as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

The Copalis CMV Total Antibody Assay is based on the principle of antibodydependent particle aggregation as detected by measurement of changes in light scattering. Latex particles coated with inactivated CMV antigens aggregate in the presence of antibodies to CMV. After 10 minutes of agitation, the level of aggregation is determined by measurement of the number of reacted and unreacted particles as they flow past a detector. The number of reacted particles is related to the level of CMV antibodies present in the test specimen. Without prior infection, antibody levels are absent or low. After infection, antibody levels rise and usually remain stable (but declining in titer) for years. Reactivity is assessed by the level of aggregation relative to a cutoff value. The Copalis CMV Assay detects the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor proficiency.

Here's a breakdown of the acceptance criteria and study details for the Copalis™ CMV Total Antibody Assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details

1. Sample Size Used for the Test Set and Data Provenance:

• Clinical Comparison: 689 patient sera samples.
  • Provenance: Samples represented the mid-Atlantic and Gulf Coast regions of the U.S. (likely retrospective, as they are "patient sera samples" and not explicitly stated as prospectively collected for this study, though it's not definitively stated. The context of "tested at 2 clinical laboratories" implies existing samples).
• Reproducibility: 4 samples for general reproducibility (likely internal reference samples, not human patient samples). 30 sets of simulated acute and convalescent pairs for seroconversion reproducibility.
• CDC CMV Serum Panel: 1 panel, composition not specified but mentioned as "66% positive and 34% negative samples" (implies a total size for the panel, but not the exact number of individual samples within it).

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

• Clinical Comparison: The ground truth for relative sensitivity and specificity was established by the Becton Dickinson and Co. CMVscan Test (the predicate device). No information is provided about human expert involvement in establishing ground truth for the 689 patient samples, as the comparison is against an existing diagnostic test.
• CDC CMV Serum Panel: The panel was "characterized" by the CDC. No information on the number or qualifications of experts involved in the CDC's characterization or ground truth establishment.

3. Adjudication Method for the Test Set:

• Clinical Comparison: Not explicitly stated. The comparison is directly between the Copalis assay and the predicate device. There is no mention of a third adjudicator for discordant results.
• Reproducibility & CDC Panel: Not applicable, as these studies focused on agreement with known values or reproducibility, not a diagnostic decision requiring adjudication.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

• No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an in-vitro diagnostic assay for antibody detection, not an imaging or diagnostic aid that involves human readers interpreting output.

5. If a Standalone (algorithm only without human-in-the-loop performance) was done:

• Yes, this is a standalone device. The Copalis™ CMV Total Antibody Assay is an automated immunoassay system. Its performance (sensitivity, specificity, reproducibility) is measured directly without human interpretation of the assay's output. The "human-in-the-loop" would be the laboratory technician running the assay and interpreting the quantitative results per the device's cutoff values, but the performance metrics provided reflect the device's analytical capability.

6. The Type of Ground Truth Used:

• Clinical Comparison: The ground truth was established by the results of the Becton Dickinson and Co. CMVscan Test (predicate device).
• Reproducibility: The ground truth was based on pre-defined reference standards (e.g., control samples with expected reactivity levels, simulated acute/convalescent pairs with known seroconversion status).
• CDC CMV Serum Panel: The ground truth was the "characterized" results from the CDC CMV Serum Panel.

7. The Sample Size for the Training Set:

• The document does not report information about a training set. This is common for traditional immunoassay development, where performance is optimized through assay formulation and component selection, rather than through machine learning models that require distinct training and testing datasets.

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

• Since no training set is reported, this information is not applicable.

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