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The Trinity Biotech Captia™ Measles IgM Enzyme-Linked Immunosorbent Assay (ELISA) is intended for the qualitative detection of Measles IgM antibodies in human serum of patients suspected of measles (rubeola) infection. This assay is intended for use as an aid in the diagnosis of a current or recent measles (rubeola) infection in conjunction with other clinical information and laboratory findings.

Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at a point of care. This test is not intended for use in screening blood and plasma donors.

The Trinity Biotech Captia™ Measles IgM test is an Enzyme-Linked Immunosorbent Assays (ELISA). When measles antigen (Edmonston strain) is bound to the solid phase and brought into contact with a patient's serum, antigen specific antibody, if present, will bind to the antigen on the solid phase forming antibody complexes. Excess antibody is removed by washing. This is followed by the addition of goat anti-human IgM globulin conjugated with horseradish peroxidase which will bind to the antibody-antigen complexes. The excess conjugate is removed by washing, followed by the addition of Chromogen/Substrate tetramethylbenzidine (TMB). If specific antibody to the antigen is present in the patient's serum, a blue color develops. When the enzymatic reaction is stopped with 1N H2SO4. The contents of the wells turn yellow. The color, which is indicative of the concentration of antibody in the serum, can be read on a suitable spectrophotometer or ELISA microwell plate reader.

Here's an analysis of the acceptance criteria and the studies performed for the Trinity Biotech Captia™ Measles IgM ELISA Test Kit, presented in the requested format:

Acceptance Criteria and Device Performance for Trinity Biotech Captia™ Measles IgM ELISA

The provided document describes the performance characteristics and clinical studies of the Trinity Biotech Captia™ Measles IgM ELISA. The acceptance criteria are not explicitly stated as pass/fail thresholds in a dedicated table, but are inferred from the reported performance characteristics.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Test Set (Clinical Studies 1 & 2): 188 samples from suspected measles infection cases.
  • Data Provenance: Retrospective, collected from individuals in whom a measles IgM test was ordered by the Texas Department of Health, Austin, Texas (66 samples) and the State Laboratory of Public Health in Raleigh, North Carolina (122 samples), USA.
• Test Set (Clinical Study 3): 8 samples.
  • Data Provenance: Retrospective, collected from submissions to the Kansas Department of Health and Environment Laboratory (KDHE), Topeka, Kansas, USA.
• Test Set (Specificity in a Normal Population): 200 random serum samples.
  • Data Provenance: Not explicitly stated, but implied to be from a general population (individuals between ages 18-65 with no known clinically apparent Measles infection). Location not specified.
• Test Set (Cross-Reactivity): 47 samples.
  • Data Provenance: Confirmed positive for other IgM antibodies (CMV, HSV1, HSV2, Rubella, VZV, Mumps, Parvo-B19) by Trinity Biotech Captia™ test kits. Location not specified.
• Test Set (Precision/Reproducibility): 6 blinded panel members (4 low-to-moderate positive, 2 negative).
  • Data Provenance: Not specified, likely internal or commercially sourced panels.

3. Number of Experts and Qualifications for Ground Truth

• The document does not specify the number of experts used to establish the ground truth for the test sets in the clinical studies.
• The ground truth in Clinical Studies 1 & 2 was established using a "comparator testing algorithm" which consisted of "the results of other laboratory confirmation methods including comparator Measles IgM ELISA test kit, a comparator Measles IgM IFA test kit, Complement Fixation (CF), Hemagglutionation Inhibition (HI) and the Trinity Biotech Captia™ Measles ELISA IgG test kit." This implies multiple laboratory results were used to form a consensus or a defined algorithm, rather than individual expert adjudication of each case.
• Similarly, in Clinical Study 3, the "comparator algorithm included RNA polymerase chain reaction (PCR) on urine, nasopharyngeal swab (NPS) and/or throat swab (TS) samples."

4. Adjudication Method for the Test Set

• For Clinical Studies 1 & 2, the ground truth was established by a "comparator algorithm" based on multiple laboratory confirmation methods (e.g., other ELISAs, IFA, CF, HI). The specific adjudication rule (e.g., 2 out of 3, 3 out of 4) is not explicitly detailed, but it generally implies a form of consensus derived from multiple test results rather than human expert adjudication.
• For Clinical Study 3, the ground truth was established by a "comparator algorithm" based on PCR results from various sample types. Again, the specific adjudication rules for discrepant PCR results (e.g., "NPS negative at two sites, urine positive at one site and urine indeterminate at one site") are not explicitly detailed for how the final "positive," "indeterminate," or "negative" comparator algorithm result was reached.

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

• No, an MRMC comparative effectiveness study was not performed. This device is an Enzyme-Linked Immunosorbent Assay (ELISA), which is an automated or semi-automated laboratory test. It does not involve human readers interpreting images or data where AI assistance would be applicable in the traditional sense of an MRMC study for imaging diagnostics. The "readers" are the laboratory technicians operating the ELISA equipment.

6. Standalone Performance Study

• Yes, standalone performance was done for the device. All reported performance metrics (analytical performance, seroconversion, cross-reactivity, clinical agreement with comparator algorithms) represent the performance of the Captia™ Measles IgM ELISA as an algorithm/device only, without human "in-the-loop" assistance for interpreting the result of the ELISA itself. While humans perform the test and interpret the final ISR value against predefined cut-offs, the "algorithm" is determining the ISR.

7. Type of Ground Truth Used

• The ground truth used was a combination of other laboratory confirmation methods and algorithms.
  • For Clinical Studies 1 & 2: "comparator testing algorithm used at each institution to determine the presence of current or recent measles infection" which included "comparator Measles IgM ELISA test kit, a comparator Measles IgM IFA test kit, Complement Fixation (CF), Hemagglutionation Inhibition (HI) and the Trinity Biotech Captia™ Measles ELISA IgG test kit." This represents a form of expert-defined algorithm/consensus from multiple laboratory tests.
  • For Clinical Study 3: "comparator algorithm included RNA polymerase chain reaction (PCR) on urine, nasopharyngeal swab (NPS) and/or throat swab (TS) samples." This is essentially molecular pathology/laboratory results.
  • For Cross-Reactivity: Confirmed positive status based on other specific IgM ELISA tests.
  • For Seroconversion: A commercially available seroconversion panel.

8. Sample Size for the Training Set

• The document does not explicitly state a separate "training set" in the context of machine learning model development. This is an ELISA kit, not typically a machine learning algorithm that requires a distinct training phase in the same way. The development and optimization of the assay (e.g., antigen titration, calibrator development, component formulation) would be part of an iterative development process that could be considered analogous to "training," but not in the sense of a labeled dataset for an AI model.
• The cut-off determination study involved 228 Measles IgM negative sera, which were used to establish the positive threshold (mean + 4SD). This could be considered a form of "training" or "calibration" data for the assay's interpretive criteria.

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

• As noted above, there isn't a traditional "training set" for a machine learning algorithm.
• For the cut-off determination, the 228 Measles IgM negative sera were explicitly described as "Measles IgM negative sera" and were used to calculate statistical parameters (mean and standard deviation of optical density readings) to define the initial positive threshold. Four samples were disqualified because they were in the equivocal range on Trinity IgM ELISA or indeterminate on a comparator Measles IFA test kit (due to non-specific staining). This implies an initial screening or pre-classification of these samples as "negative" before their use in cut-off calculation. The final cut-off was derived using these empirical observations.

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The BioPlex™ 2200 MMRV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and EDTA or heparinized plasma. The BioPlex 2200 MMRV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.

This kit is intended as an aid in the determination of serological status to Measles, Mumps, Rubella, and VZV. This kit is not intended for use in screening blood or plasma donors.

The performance of this assay has not been established for use in neonates, pediatrics and immunocompromised patients, or for use at point of care facilities.

The BioPlex 2200 MMRV IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Four (4) different populations of dyed beads are coated with antigens to identify the presence of IgG class antibodies associated with Measles, Mumps, Rubella and Varicella-zoster. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, anti-human IgG antibody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are resuspended in wash buffer. The bead mixture then passes through the detector.

The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI). Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum to the reaction vessel and the absence of significant non-specific binding in serum.

The instrument is calibrated using a set of three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories.

The BioPlex 2200 MMRV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and EDTA or heparinized plasma. It is intended for use with the Bio-Rad BioPlex 2200 System as an aid in determining serological status to these viruses. It is not intended for screening blood/plasma donors, and performance has not been established for neonates, pediatrics, immunocompromised patients, or point-of-care facilities.

Here's an analysis of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria (e.g., minimum sensitivity/specificity percentages). Instead, the performance is demonstrated through comparative testing against legally marketed predicate devices and reproducibility studies. The tables below summarize the reported device performance.

Comparative Testing: BioPlex 2200 MMRV IgG vs. Commercially Available EIAs

Retrospective Negative Samples: BioPlex 2200 MMRV IgG vs. EIA

Reproducibility (Total %CV for Serum, across sites, days, runs)

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

• Prospective Comparative Testing:
  • Pregnant Women: N = 396 serum samples. Data provenance: Not explicitly stated, but the study was conducted at 3 U.S. clinical trial sites. Retrospective or prospective nature is not specified for collection.
  • Measles, Mumps, Rubella, or VZV Test Ordered: N = 1183 serum samples. This population included (N = 790) samples submitted for routine testing and (N = 393) samples for pre-employment evaluation. Data provenance: Not explicitly stated, but the study was conducted at 3 U.S. clinical trial sites.
• Retrospective Comparative Testing (Negative Samples):
  • Measles IgG: N = 93 serum samples.
  • Mumps IgG: N = 96 serum samples.
  • Rubella IgG: N = 268 serum samples.
  • VZV IgG: N = 143 serum samples.
  • Data provenance: Not explicitly stated, but implies these were pre-existing samples.
• CDC Rubella Evaluation Serum Panel: N = 100 serum samples (82 positive, 18 negative). Data provenance: Provided by the CDC.
• Reproducibility Studies: A "reproducibility panel" was prepared, consisting of positive panel members in serum, EDTA plasma, and sodium heparin plasma, along with a positive and negative control. The exact number of panel members is not explicitly stated beyond "varying levels of antibodies" and a "positive control." Each panel member and controls were tested in quadruplicate on 1 run per day over 5 days at each of 3 sites (4 replicates x 1 run x 5 days x number of panel members = total Sample N for reproducibility analysis, which for each measured point was N=60).

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

The ground truth for the comparative testing was established using commercially available EIA (Enzyme Immunoassay) predicate devices, which are conventional laboratory tests. No human experts establishing a ground truth in the manner of, for example, radiologists interpreting images, are mentioned for these studies.

For the CDC Rubella Evaluation Serum Panel, the samples were "masked, characterized" by the CDC. This implies expert characterization by the CDC, but the specific number and qualifications of experts are not described.

4. Adjudication Method for the Test Set

• Prospective Comparative Testing:
  • For Mumps and Measles, equivocal results on the commercially available EIAs were "further tested on two additional commercially available EIAs for consensus." This implies a 2 out of 3 consensus method for adjudicating equivocal results from the primary predicate EIA, using the two additional EIAs. The exact consensus rule (e.g., majority or all agree) is not explicitly stated but "consensus" suggests agreement among at least two.
  • For Rubella, equivocal results on the commercially available EIA were "re-tested on the commercially available EIA, following the manufacturer's recommendations." This is a re-testing procedure, not a multi-reader adjudication.
  • For VZV, no specific adjudication method for equivocal results is mentioned in the tables provided.
• Retrospective Comparative Testing:
  • For Measles and Mumps negative samples, they were "selected using a consensus of two out of three commercially available EIAs." This is a pre-selection method for the test samples based on consensus, rather than adjudication of results from the BioPlex device.
  • For Rubella and VZV negative samples, they were "selected using the respective commercially available EIAs used for the comparative analysis." No consensus method is mentioned here for selection.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Its Effect Size

No MRMC comparative effectiveness study was described. The study focuses on comparing the BioPlex device's performance to existing immunoassays, rather than assessing human reader performance with and without AI assistance.

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

Yes, the studies described are standalone performance evaluations of the BioPlex 2200 MMRV IgG kit against predicate devices. The device is an automated immunoassay system, and its performance metrics (agreement, reproducibility) reflect its standalone operational capabilities. There is no human-in-the-loop component mentioned in its operational or evaluation methodology that would constitute an "AI assistance" scenario.

7. The Type of Ground Truth Used

The primary ground truth for evaluating the BioPlex 2200 MMRV IgG kit's performance was established using results from legally marketed, commercially available EIA (Enzyme Immunoassay) predicate devices.

• For Measles and Mumps, this involved consensus results from two out of three commercially available EIAs for equivocal samples.
• For Rubella, re-testing with the predicate EIA was used for equivocal results.
• For the CDC Rubella panel, the ground truth was "masked, characterized" CDC reference sera.

8. The Sample Size for the Training Set

No training set is explicitly mentioned, as this is a traditional immunoassay device, not a machine learning or AI-driven algorithm in the context of typical training/validation/test sets for pattern recognition. The device is calibrated using a "set of three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories" and controls are used for quality assurance.

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

Since no traditional "training set" in the context of AI/ML was used, this question is not applicable. The device's operational parameters are based on established immunoassay principles, calibration, and quality control using defined calibrator and control materials.

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