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The ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test is an in vitro, rapid, lateral flow test, also known as a lateral flow immunochromatographic assay, intended for the qualitative detection of Streptococus pneumoniae and Legionella pneumophila antigens in urine specimens with symptoms of pneumonia. The assay is intended to aid in diagnosis of S. pneumoniae and L. pneumophila serogroup 1 infections. The assay is further intended to aid in the diagnosis of S. pneumoniae infection of S. pneumoniae antigen in cerebrospinal fluid (CSF). Results from the ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test should be interpreted in conjunction with the patient's clinical evaluation and other diagnostic methods.

ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test is a rapid lateral flow test for qualitative detection of S. pneumoniae in human urine and CSF samples and L. pneumophila (primarily serogroup 1) antigens in human urine samples. The test is effective in presumptive diagnosis of pneumococcal pneumonia caused by S. pneumoniae or Legionella pneumonia (Legionnaires' disease) caused by L. pneumophila, in conjunction with culture and other methods. Correct and early treatment is vital for the prognosis of both diseases and therefore quick methods to confirm both diseases in the initial phase are very important in order to initiate the proper antibiotic treatment as soon as possible.

This document describes the validation of the ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test, an in vitro lateral flow immunochromatographic assay.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device are implicitly demonstrated by the reported sensitivities and specificities, and positive/negative percent agreements achieving certain levels across various studies (retrospective, prospective, analytical). While explicit numerical acceptance criteria are not stated in a dedicated table, the consistently high performance metrics across both S. pneumoniae and L. pneumophila detection in urine and CSF demonstrate the device's acceptable performance.

Here's a summary of the reported device performance, which serves as evidence of meeting implicit acceptance criteria:

Table 1: Summary of ImmuView S. pneumoniae and L. pneumophila Urinary Antigen Test Performance

2. Sample Sizes and Data Provenance

• Retrospective Study (Urine Samples):

  • S. pneumoniae: 100 culture-positive urine samples (48 from Sweden, 52 from Denmark, all from blood culture positive patients). 221 known negative urine samples.
  • L. pneumophila: 98 culture-confirmed urine samples (55 from Europe, 43 from the United States (US), these 43 were previously determined positive in a urinary antigen test). 240 known negative urine samples.
  • Data Provenance: Retrospective, samples from Europe (Sweden, Denmark) and the United States.

• Prospective Study (Urine Samples):

  • Total Samples: 306 freshly collected urine samples (with 92 having to be frozen before testing due to practicalities).
  • Data Provenance: Prospective, collected from two sites in Spain and Denmark. These were from "all comers" at risk of community-acquired pneumonia.

• Clinical Study (CSF Samples):

  • S. pneumoniae: 14 culture-positive CSF specimens (9 from US labs, 5 from European labs). 169 known negative CSF samples (113 from US labs, 56 from European labs).
  • Data Provenance: Retrospective/Clinical, samples from US and Europe.

• Spiked CSF Testing:

  • S. pneumoniae: 50 human CSF samples spiked at the LOD. 10 additional unspiked negative CSF samples.

• Analytical Studies (Cross-Reactivity, LOD, Interfering Substances, Strain Reactivity): Sample sizes vary by test and are described in the relevant sections (e.g., 143 samples for cross-reactivity with spiked bacteria/viruses in urine, 47 interfering agents tested).

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth. However, the ground truth for clinical studies (both retrospective and prospective) is defined as culture-confirmed results for S. pneumoniae and L. pneumophila infections, and "known negative" samples based on culture.

For the CSF study, patients were "suspected of meningitis," and the ground truth was also culture-confirmed S. pneumoniae.

Given that these are in vitro diagnostic tests, the "experts" in establishing ground truth would primarily be laboratory personnel performing culture confirmation, which is the gold standard for defining infection status.

4. Adjudication Method

The document does not describe any specific adjudication method (e.g., 2+1, 3+1 concensus) for establishing the ground truth for the test sets. The ground truth appears to be based on culture results, which typically do not require adjudication by multiple human interpreters in the same way imaging studies might.

For the reproducibility study, the reading and interpretation of the panels were performed visually by operators. Errors in reading (e.g., operator interpreted S. pneumoniae Band result as negative even though band was present) are mentioned, indicating potential for individual variability, but a formal adjudication process for disagreements is not explicitly stated beyond what happens when "invalid" results occur.

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

No multi-reader, multi-case (MRMC) comparative effectiveness study was performed or described. This device is an in vitro diagnostic (IVD) lateral flow assay, which is primarily a standalone test designed to provide a direct result, not an AI-assisted diagnostic tool for human readers. Therefore, there is no discussion of how human readers' performance might improve with AI assistance.

6. Standalone Performance

Yes, extensive standalone performance testing was done. The entire study described focuses on the "algorithm only" (i.e., the ImmuView test's intrinsic performance) without human-in-the-loop assistance for interpretation. The results in the tables for sensitivity, specificity, and agreement are all measures of the device's standalone performance against established ground truth (culture or comparator tests).

7. Type of Ground Truth Used

The primary type of ground truth used was culture confirmation for S. pneumoniae and L. pneumophila from urine and CSF samples.

• Urine Retrospective Study: Culture-positive urine samples (blood culture positive for S. pneumoniae, culture confirmed for L. pneumophila) and known negative (culture confirmed negative) urine samples.
• CSF Clinical Study: Culture-positive CSF specimens.
• Prospective Study: Comparison with other lateral flow urine antigen tests (Comparator) was used, implying the Comparator's results served as an indirect ground truth or reference in this specific study, although the retrospective studies relied on culture.
• Analytical Studies: Ground truth was based on known concentrations of purified antigens (pg/mL, ng/mL) or specific colony-forming units (CFU/mL) for LOD and strain reactivity, and known substances/organisms for cross-reactivity and interfering substances.

8. Sample Size for Training Set

The document does not explicitly mention a "training set" in the context of an algorithm or AI development. This product is a lateral flow immunoassay, a biochemical test, not a machine learning algorithm that undergoes a training phase. Therefore, the concept of a "training set" as it pertains to AI/ML models is not applicable here. The samples described were used for validation and performance evaluation.

9. How Ground Truth for Training Set Was Established

As explained under point 8, the product is a lateral flow immunoassay, not an AI/ML model. Therefore, there is no "training set" in the computational sense, and thus no ground truth establishment specific to a training set for an algorithm. All samples were used for validation and performance assessment, with ground truth established primarily by culture confirmation as described in point 7.

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The TRU LEGIONELLA® assay is an in vitro, rapid, lateral-flow immunoassay for the qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine specimens from patients with symptoms of pneumonia. Test results are to be used as an aid in diagnosis of Legionella serogroup 1 infection. A negative result does not preclude infection with Legionella pneumophila serogroup 1. Test results are to be used in conjunction with information obtained from the patient's clinical evaluation and other diagnostic procedures.

The TRU LEGIONELLA® assay is an in vitro, rapid, lateral-flow immunoassay.

This is a letter acknowledging the receipt of a 510(k) premarket notification for a medical device called "Legionella. Spp., Elisa." While it indicates that the device has been found substantially equivalent to a predicate device, this document does not contain the detailed study information, acceptance criteria, or performance data that you requested.

The letter explicitly states: "We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent...". This means the FDA has evaluated the submission and deemed the device safe and effective for its stated indications based on comparisons to a legally marketed predicate. However, the supporting data and studies are part of the original 510(k) submission and are not publicly detailed in this acknowledgment letter.

Therefore, I cannot extract the requested information from the provided text. To obtain that level of detail, you would typically need to review the actual 510(k) summary and supporting documentation submitted by Meridian Bioscience, Inc. to the FDA, which is usually found in a separate, more comprehensive public document associated with the 510(k) number (K163273).

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The TRU Legionella assay is an in vitro, rapid, lateral-flow immunoassay for the qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine specimens. It is designed to test specimens from patients with symptoms of pneumonia. Test results are to be used as an aid in diagnosis of Legionella pneumophila serogroup 1 infection. A negative result does not preclude infection with Legionella pneumophila serogroup 1. Test results are to be used in conjunction with information obtained from the patient's clinical evaluation and other diagnostic procedures.

The TRU Legionella assay is an in vitro, rapid, lateral-flow immunoassay for the qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine specimens. The assay consists of Test Strips containing anti-Legionella pneumophila serogroup 1 as the capture antibody, Containing anti-Legionella pneumophila serogroup 1 as the detection antibody, Sample Diluent/Negative Control, and Positive Control.

The provided text describes the performance of the TRU Legionella assay, an in vitro rapid lateral-flow immunoassay for the qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine specimens. The study aims to demonstrate substantial equivalence to a predicate device, the BinaxNOW® Legionella Urinary Antigen test.

Here's an analysis based on your requested points:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific percentages for positive or negative agreement. Instead, it presents the performance of the TRU Legionella assay in comparison to the predicate device, the BinaxNOW® Legionella test, and demonstrates high correlation. The overall performance metrics serve as the reported device performance.

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

• Test Set Sample Size: 428 qualified patient samples.
• Data Provenance:
  • Country of Origin: Southeastern regions of the United States and the Netherlands.
  • Retrospective/Prospective: The US clinical trial sites evaluated both retrospective frozen samples and prospectively collected samples. The retrospective samples were those previously submitted for Legionella testing. The site in the Netherlands evaluated 220 frozen samples from a well-characterized repository.

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

The ground truth for the clinical study was established by comparison to the Binax NOW® Legionella Urinary Antigen test (predicate device). The document does not describe the use of independent experts to establish ground truth for this comparison study, as it's a comparative effectiveness study against a legally marketed device. The predicate device itself serves as the reference standard for "truth" in this context.

For the samples from the Netherlands, they were "chosen from a well characterized repository of urine samples collected from patients with confirmed Legionnaires Disease as well as negative specimens from patients suspected of infection by Legionella," implying an existing clinical diagnosis. However, the exact number and qualifications of experts involved in the initial confirmation of these Legionnaires' Disease cases are not specified in this document.

4. Adjudication Method for the Test Set

Not applicable. The study is a direct comparison of the TRU Legionella assay's results against the BinaxNOW® Legionella test. There is no mention of an adjudication method involving multiple readers or experts to resolve discrepancies between the two tests. The BinaxNOW® result is treated as the reference.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed to assess human reader improvement with AI assistance. This document describes the performance of an in vitro diagnostic (IVD) rapid immunoassay, not an AI-powered diagnostic imaging or interpretation tool. The test is visually read by a single operator, and the comparison is between the new device and a predicate device.

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

Yes, this is effectively a standalone performance study. The TRU Legionella assay is an in vitro rapid lateral-flow immunoassay designed for direct visual interpretation of results. Its performance is measured independently against the predicate device without human-in-the-loop assistance for the assay itself (beyond the visual reading as intended).

7. Type of Ground Truth Used

The primary ground truth used for the clinical performance comparison was the results from the predicate device, BinaxNOW® Legionella Urinary Antigen test. For the samples from the Netherlands, the repository samples were "from patients with confirmed Legionnaires Disease," suggesting clinical diagnosis/outcomes data for positive cases, and "negative specimens from patients suspected of infection by Legionella" for negative cases.

8. Sample Size for the Training Set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI development. This is a traditional IVD device. The analytical studies (sensitivity, interference, cross-reactivity, strain reactivity) involve testing numerous laboratory-prepared specimens, but these are for analytical validation rather than AI model training.

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

Not applicable, as this is a traditional IVD device and not an AI-based system involving a training set in the machine learning sense. The analytical studies establishing limits of detection, interference, and cross-reactivity use known concentrations of L. pneumophila strains or other substances, which are internally controlled ground truths established through laboratory methods.

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The Clearview Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.

The Clearview® Exact II Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory swab specimens. These antibodies and a control protein are immobilized onto a membrane support as three distinct lines and are combined with other reagents/pads to construct a Test Strip. Nasal swab samples are added to a Coated Reaction Tube to which an extraction reagent has been added. A Clearview Exact II Influenza A & B Test Strip is then placed in the Coated Reaction Tube holding the extracted liquid sample. Test results are interpreted at 10 minutes based on the presence of pink-to-purple colored Sample Lines. The yellow Control Line tums blue in a valid test.

Here's a breakdown of the acceptance criteria and the study details for the Clearview® Exact II Influenza A & B Test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in numerical terms (e.g., "Sensitivity must be > 90%"). Instead, it presents the device's performance against a gold standard (viral culture) as the evidence for substantial equivalence. The predicate device's performance often serves as an implicit benchmark for acceptance.

However, we can infer what constitutes acceptable performance from the presented results, as there's no indication that the results were unacceptable.

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

• Sample Size: 486 prospective specimens
• Data Provenance:
  • Country of Origin: U.S. (multi-center, seven trial sites)
  • Retrospective or Prospective: Prospective study, conducted during the 2008-2009 respiratory season. Specimens were collected from symptomatic patients.

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

The document does not explicitly state the number or specific qualifications of experts involved in establishing the ground truth. It relies on viral culture as the ground truth. Viral culture is a laboratory method, not typically performed by "experts" in the sense of clinicians or radiologists, but by trained laboratory personnel.

4. Adjudication Method for the Test Set

The document does not mention an explicit adjudication method (e.g., 2+1, 3+1). The primary comparison is the Clearview® Exact II test result directly against the viral culture result. For discrepant results with Influenza B (19 samples positive by culture, negative by Clearview), an investigational RT-PCR assay was used as a secondary check, showing 10 of these were negative by PCR. This suggests a form of post-hoc investigation for specific discrepancies, rather than a pre-defined adjudication process, but not a consensus reading among multiple human readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a standalone performance evaluation of a rapid diagnostic test against a gold standard (viral culture), not a study involving human readers or AI assistance.

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

Yes, a standalone performance study was done for the device. The Clearview® Exact II Influenza A & B Test is itself a rapid immunoassay, a "device-only" test. The "performance vs. viral culture" is the standalone performance of the diagnostic test without human interpretation of complex images or data beyond reading simple color lines.

7. The Type of Ground Truth Used

The ground truth used for the clinical study was Viral Culture. For the 19 discrepant Influenza B samples, an investigational RT-PCR assay was also used as a secondary reference.

8. The Sample Size for the Training Set

The document does not mention a separate "training set" for the clinical performance evaluation. The clinical study described is a prospective validation set. For a device like this, the "training" (development and optimization) would typically involve internal efforts during the assay development process, using laboratory-prepared samples or retrospective samples, but a dedicated "training set" for clinical evaluation is not described for this type of diagnostic device.

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

As no specific "training set" for clinical performance is described, the method for establishing its ground truth is not provided. For analytical studies (e.g., analytical sensitivity, reactivity), the ground truth is typically precisely quantified viral cultures or preparations.

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The SAS™ Legionella Test is a visually read, in vitro immunochromatographic rapid assay for the presumptive qualitative detection of Legionella pneumophila serogroup 1 antigens in human urine. This test is intended to aid in the presumptive diagnosis of Legionnaires' disease in conjunction with culture and other methods for patients with signs and symptoms of pneumonia. This test is for prescription use only.

The SAS™ Legionella test utilizes a combination of polyclonal antibodies against the antigens of Legionella pneumophila. The SAS™ Legionella test begins with the addition of urine to the test device. The specimen is absorbed by the sample pad and then moves through the conjugate pad which contains dried gold conjugated antibodies which are specific for Legionella pneumophila antigens; if the Legionella antigens are present in the urine sample, a "half-sandwich" immunocomplex is formed. This immuno-complex then migrates via capillary action along a nitrocellulose membrane containing immobilized antibodies to Legionella pneumophila antigens. The immobilized antibodies bind the "half-sandwich" immuno-complex to form a "whole sandwich" immuno-complex. Thus, when the "whole sandwich" is formed, a visible, pink colored line develops in the specimen zone on the test device. In the absence of a Legionella antigen, a "sandwich" immuno-complex is not formed and a negative result is indicated. To serve as a procedural control, a pink colored control line will always appear in the control zone regardless of the presence or absence of Legionella antigen. The test is available in cassette format.

{
  "1_table_of_acceptance_criteria_and_reported_device_performance": {
    "Acceptance Criteria (Implicit)": "To demonstrate substantial equivalence to the predicate device (Binax™ Now® Legionella Urinary Antigen Test) and to culture methods for the detection of Legionella pneumophila serogroup 1 antigens in human urine.",
    "Reported Device Performance": "The SAS™ Legionella Test performed substantially equivalent to the predicate device, Binax™ Now® Legionella Urinary Antigen Test and to culture. Cross reactivity and interference studies showed no interference or cross-reaction with common viral and bacterial strains found in human urine."
  },
  "2_sample_size_used_for_the_test_set_and_data_provenance": {
    "Sample Size (Test Set)": "Not explicitly stated. The document mentions \"frozen and fresh urine specimens\" were used for comparison but does not provide a specific number.",
    "Data Provenance": "Not explicitly stated (e.g., country of origin). The data is retrospective based on the use of \"frozen and fresh urine specimens\" for comparison."
  },
  "3_number_of_experts_used_to_establish_the_ground_truth_for_the_test_set_and_qualifications": "Not applicable. The ground truth was established by comparison to a predicate device (Binax™ Now® Legionella Urinary Antigen Test) and culture methods, not by expert interpretation of the device results.",
  "4_adjudication_method_for_the_test_set": "Not applicable. Adjudication methods like 2+1 or 3+1 are typically used for expert consensus on image interpretation, which is not relevant for this immunochromatographic rapid assay.",
  "5_if_a_multi_reader_multi_case_mrmc_comparative_effectiveness_study_was_done": "No. This is an immunochromatographic rapid assay, not an imaging device requiring human reader interpretation in a MRMC study.",
  "6_if_a_standalone_performance_study_was_done": "Yes. The performance of the SAS™ Legionella Test (algorithm only, as it's a diagnostic kit) was directly compared against established methods (predicate device and culture) for diagnostic accuracy.",
  "7_the_type_of_ground_truth_used": "Comparison to a legally marketed predicate device (Binax™ Now® Legionella Urinary Antigen Test) and culture methods. Culture is generally considered a gold standard for bacterial identification.",
  "8_the_sample_size_for_the_training_set": "Not applicable. As a diagnostic test kit, there isn't a 'training set' in the machine learning sense. The device is developed through biochemical assays and optimizations, not by training an algorithm on a 'training set' of data.",
  "9_how_the_ground_truth_for_the_training_set_was_established": "Not applicable. See #8. The development of such a test relies on established scientific principles of immunology and antigen-antibody reactions, and validation against known Legionella-positive and -negative samples, rather than a 'ground truth' established for a training set in machine learning."
}

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The Binax NOW® Legionella Urinary Antigen Test is an in vitro rapid immunochromatographic assay for the qualitative detection of Legionella serogroup 1 antigen (L. pneumophila serogroup 1 antigen) in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of Legionella infection ("Legionnaires" Disease) caused by L. pneumophila serogroup 1 in conjunction with culture and other methods.

The Binax NOW® Legionella Urinary Antigen Test is an immunochromatographic membrane assay to detect Legionella pneumophila serogroup 1 antigen in human urine. A test strip, containing gold-conjugated and immobilized anti-Legionella pneumophila serogroup 1 antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A Dacron swab is dipped into the urine to be tested and then inserted into the swab well. A single reagent is added to the swab well from a dropper bottle before closing the test device. Legionella urinary antigen captured by immobilized anti-Legionella pneumophila antibody reacts to bind anti-Legionella pneumophila conjugated antibody, forming the Sample Line. Immobilized control antibody captures anti-species conjugate, forming the Control Line. There are no transferring steps, the sample is contained, and results are available in 15 minutes.

This document describes the Binax NOW® Legionella Urinary Antigen Test, an immunochromatographic assay for detecting Legionella pneumophila serogroup 1 antigen in urine specimens. The 510(k) submission (K070522) aimed to demonstrate substantial equivalence to the unmodified Binax NOW® Legionella Urinary Antigen Test (K982238) after modifications to the device.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Test Set (Method Comparison):

  • Negative Samples: 70 urine samples
  • Positive Samples: 15 known positive urine specimens
  • Data Provenance: The document states that the negative urine samples were "collected from presumed healthy individuals." The provenance of the positive samples is not explicitly detailed but they are described as "known positive urine specimens." It is retrospective data as it describes samples that were already collected and classified. The country of origin is not specified.

• Test Set (Cross-Reactivity):

  • Number of Organisms Tested: 11
  • Concentrations: Ranged from 1 x 10^6 to 2 x 10^3 (depending on the organism).
  • Data Provenance: Whole organism cross-reactivity testing was performed. The organisms were grown in culture. Details on the origin of the cultures or their geographical provenance are not provided.

• Test Set (Loss of Signal):

  • Positive Urine Specimen: 1
  • Lots Tested: 3 separate lots of the modified device.
  • Data Provenance: Serial two-fold dilutions of a known positive urine specimen. Details on the origin of the specimen are not provided.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth for the test sets. For the method comparison study, "known positive urine specimens" and "presumed healthy individuals" were used, implying prior methods established positivity and negativity. For cross-reactivity, organisms were grown in culture, indicating laboratory-derived ground truth. For loss of signal, a "known positive urine specimen" was used.

4. Adjudication Method

No adjudication method is described for the test sets. The studies rely on direct comparison to the predicate device or established laboratory standards.

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

No MRMC comparative effectiveness study was mentioned or performed. This device is an in vitro diagnostic (IVD) test, not an imaging device or an AI application designed to assist human readers in interpretation. Therefore, the concept of human readers improving with AI vs without AI assistance is not applicable here.

6. Standalone Performance

Yes, a standalone performance assessment was conducted for the modified device by comparing its results directly with the unmodified predicate device, and by testing its performance in cross-reactivity and loss-of-signal experiments. The device itself generates a qualitative result (positive/negative) without human interpretation in the loop to determine the primary outcome of the test.

7. Type of Ground Truth Used

The ground truth used appears to be a combination of:

• Predicate Device Comparison: For the method comparison, the results of the unmodified predicate device served as the established "truth" for agreement.
• Pre-classified Samples: "Known positive urine specimens" and urine from "presumed healthy individuals" imply prior diagnostic classification or health status determining the ground truth for these samples.
• Laboratory-derived Standards: For cross-reactivity, the presence or absence of specific cultured organisms at known concentrations served as the ground truth. For loss of signal, the serial dilution of a known positive specimen was used.

8. Sample Size for the Training Set

No training set is mentioned in the provided text. This device is a rapid immunochromatographic assay, not an algorithm that requires a training set in the conventional sense of machine learning. The "training" in this context would refer to the development and optimization of the assay components (antibodies, membrane, etc.) rather than a data-driven model.

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

As no training set is described or applicable in the context of this type of device, the method for establishing ground truth for a training set is not provided.

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The BD ProbeTec™ ET Legionella pneumophila (LP) Amplified DNA Assay, for use with the BD ProbeTec ET System, employs Strand Displacement Amplification (SDA) technology for the direct qualitative detection of Legionella pneumophila DNA (serogroups 1-14) in sputum specimens from patients with a clinical suspicion of pneumonia. It is intended to aid in the presumptive diagnosis of Legionnaires' disease in conjunction with culture and other methods.

The BD ProbeTec™ ET LP Amplified DNA Assay is a new test designed for use on the BD ProbeTec™ ET System. The test is indicated for use with sputum specimens from patients with a clinical suspicion of pneumonia as an aid in the presumptive diagnosis of Legionnaires' disease in conjunction with culture and other methods. The BD ProbeTecTM ET LP Amplified DNA Assay is based on the simultaneous amplification and detection of target DNA sequences using nucleic acid primers and fluorescently-labeled detector probes in a process known as strand displacement amplification (SDA). The SDA reagents are dried in two separate disposable microwells. Processed sample containing DNA is added to a Priming Microwell, which contains the amplification primers, fluorescently-labeled detector probes, and other reagents necessary for amplification. Following incubation, the reaction mixture is transferred to an Amplification Microwell, which contains two enzymes (a DNA polymerase and a restriction endonuclease) necessary for SDA. The Amplification Microwells are sealed to prevent contamination and then incubated in a thermally controlled fluorescent reader, which monitors each reaction for the generation of amplified products. Each reaction coamplifies and detects an Internal Amplification Control (IAC), as well as the target DNA. The purpose of the IAC is to verify that proper conditions exist for amplification and to reduce the possibility of reporting a false negative result due to specimen inhibitors. The presence or absence of L. pneumophila DNA is determined by calculating PAT scores (Passes After Threshold) for the specimen based on predefined threshold values. The instrument automatically reports the results as positive, negative or indeterminate.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve a sensitivity of at least X%"). Instead, it presents the determined performance metrics from a retrospective study, which presumably were considered acceptable for market clearance given the "Substantial Equivalence" finding. For the purpose of this analysis, I will treat the reported performance as the de facto "met acceptance criteria" based on the FDA's clearance.

Note on Prospective Study: The prospective study found 100% (114/114) negative agreement with culture, but as there were no culture-positive specimens, sensitivity could not be estimated. This highlights the reliance on the retrospective study for key performance metrics.

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

• Prospective Study Test Set:
  • Sample Size: 114 sputum specimens from 114 patients.
  • Data Provenance: Prospective, collected from seven clinical centers within the United States and Canada during the 2002-2003 respiratory season.
• Retrospective Study Test Set (to estimate sensitivity):
  • Sample Size: 83 retrospective sputum specimens (23 positive for L. pneumophila by culture, 60 negative by culture).
  • Data Provenance: Retrospective, acquired from clinical sites within the United States, Europe, and Canada.

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

The document does not specify the number of experts or their qualifications used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The primary ground truth for both the prospective and retrospective studies was bacterial culture.

• For the retrospective study, in cases of discordance between the BD ProbeTec™ ET LP Amplified DNA Assay and culture, Polymerase Chain Reaction (PCR) testing was performed on some of the discordant samples for further investigation. This acted as a secondary, confirmatory method, particularly when the culture was positive but the assay negative, or vice-versa. However, PCR was not uniformly applied to all discordant samples (e.g., 6 of 8 culture-negative, assay-positive samples were tested with PCR, and 1 of 2 culture-positive, assay-negative samples was tested with PCR). This suggests a form of partial adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay designed for automated detection of DNA, not an AI-assisted imaging tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

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

Yes, the performance reported is that of the standalone algorithm. The "BD ProbeTec™ ET LP Amplified DNA Assay" (which uses Strand Displacement Amplification - SDA) is an automated system that provides results ("positive, negative or indeterminate") based on predefined threshold values and calculation of "PAT scores." Human involvement is limited to sample processing and running the instrument, not interpreting raw data or making diagnostic decisions without the device's output.

7. The Type of Ground Truth Used

The primary ground truth used for both the prospective and retrospective clinical studies was bacterial culture. For discordant results in the retrospective study, PCR testing was used as a secondary, confirmatory method.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set. It mentions that "threshold values for both the L. pneumophila target DNA and the IAC were initially established using Receiver Operator Characteristic curve analyses of data obtained from positive and negative controls." These controls would constitute a form of training or calibration data, but the specific breakdown and size are not provided. The thresholds were then "verified in clinical studies and with retrospective L. pneumophila positive and negative lower respiratory specimens" and "validated in additional clinical studies."

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

The ground truth for establishing the initial threshold values (which can be considered part of the "training" or calibration) was based on positive and negative controls. The nature of these controls (e.g., cultured bacteria, synthetic DNA, confirmed clinical samples) is not detailed, but they would represent samples with known L. pneumophila presence or absence. Further verification involved "retrospective L. pneumophila positive and negative lower respiratory specimens," implying that their status (positive/negative) was also determined by a reference method, most likely culture.

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The Trinity Biotech Captia™ Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease. The assay is not intended to differentiate between the serotypes of Legionella pneumophila.

The Legionella pneumophila IgG/IgM ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative detection of total antibodies (IgG and IgM) to Legionella pneumophila serogroups 1-6 in serum from patients with clinical suspicion of Legionella Disease.

The Legionella pneumophila IgG/IgM ELISA test is an enzyme linked immunosorbent assay to detect IgG/IgM antibodies to legionella. Purified Legionella pneumophila antigen (serogroups 1, 2, 3, 4, 5, 6) is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG/IgM is added to each well. If antibody is present, it will bind to the antibody attached to the antigen on the well. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present, the substrate will undergo a color change. After an incubation period, the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

Here's a breakdown of the acceptance criteria and study details for the Trinity Biotech Legionella pneumophila IgG/IgM ELISA Test Kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity, specificity, or agreement. Instead, it presents the results of a comparative study against a predicate device (Legionella IFA) and implicitly suggests that these results demonstrate substantial equivalence. The precision study evaluates consistency rather than diagnostic accuracy.

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

• Comparative Performance Study (Site 1 - Maryland):
  • Sample Size: 33 single IFA positive sera.
  • Data Provenance: Retrospective. Samples were "from an outbreak and samples routinely submitted for Legionella testing" at a commercial R&D lab in Maryland.
• Comparative Performance Study (Site 2 - Pennsylvania):
  • Sample Size: 72 prospective serum samples.
  • Data Provenance: Prospective. Samples were "routinely submitted for Legionella testing" at a clinical laboratory in Pennsylvania.
• IFA Paired Serum Analysis (CDC Panel):
  • Sample Size: 31 serum pairs (total of 62 samples, though the analysis focuses on the 31 seroconversions).
  • Data Provenance: Presumed retrospective, from samples "submitted to CDC for titer confirmation." Origin of patients not specified, but the CDC is a US federal agency.

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

The ground truth for the test sets was established using Legionella IFA (Immunofluorescence Assay).

• The document implies that the IFA results were the established "truth" for comparison. It does not explicitly mention human experts establishing this ground truth for each individual sample, but rather relies on the accepted methodology of the IFA itself, likely performed by trained laboratory personnel.
• For the CDC Panel, the serum pairs were "confirmed to be serologically positive for an increase in titer" by IFA at the CDC. This suggests that the CDC's internal lab procedures and personnel established this confirmation. Specific qualifications of the CDC personnel are not provided.

4. Adjudication Method for the Test Set

There was no multi-expert adjudication method described for the test sets. The results of the Trinity Biotech ELISA were directly compared to the results of the Legionella IFA.

• Equivocal results from the Trinity Biotech ELISA were excluded from the agreement calculations.

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

No MRMC comparative effectiveness study was done. This study focuses on the performance of the device itself (an ELISA kit) compared to a predicate device (IFA), not on human reader performance with or without AI assistance.

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

This is a standalone study of the ELISA kit. The ELISA kit is a laboratory test with a defined output; there isn't an "algorithm" in the sense of AI that could operate without human involvement in running the test. The test results are read photometrically, and interpretation of those results to classify as positive, negative, or equivocal is inherent to the kit's design, rather than being an AI-driven interpretation.

7. Type of Ground Truth Used

The ground truth used was comparison to a predicate device (Legionella IFA).

• For the comparative performance studies, the IFA results (titer ≥ 256 for positive, < 256 for negative) served as the reference standard.
• For the CDC Panel, "seroconversion" as determined by a greater than 4-fold increase in IFA titer was the ground truth.

8. Sample Size for the Training Set

The document does not provide information about a specific "training set" or "validation set" in the context of machine learning. This is a traditional IVD device submission, where studies are designed to demonstrate performance against a reference method rather than training a model. Therefore, no explicit training set size is mentioned.

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

As no distinct training set is described for an AI/algorithm, this question is not applicable to the provided document. The performance studies described are essentially validation studies against established clinical (IFA) or commercial (R&D lab) reference points.

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Bartels Legionella Urinary Antigen ELISA Test is intended as an adjunct to culture for the presumptive diagnosis of past or current Legionnaires' Disease by qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine.

Bartels Legionella Urinary Antigen ELISA Test is an enzyme-linked immunoassay intended for the qualitative detection of Legionella pneumophila Serogroup 1 antigen in human urine. The kit consists of microelisa stripwells with lid, positive and negative control reagents, conjugate, wash concentrate, colorimetric substrate (2 components) and stop solution. Sufficient materials are provided to perform 96 analyses. The microelisa wells have been pre-coated with purified rabbit antibodies to Legionella pneumophila Serotype 1 (capture antibody). An undiluted urine specimen (100 µL), or positive or negative controls (100 µL each) are each placed in a single microelisa well followed by the addition of 50 uL of Conjugate (horseradish peroxidase-conjugated rabbit antibodies to L. pneumophila). The loaded microelisa plate is then covered with the lid and incubated for 48 to 52 minutes at 34-37°C followed by 4 cycles of wash/aspiration using diluted Wash Solution (manual or automated wash procedure). Colorimetric substrate (tetramethyl benzidine/H2O2 100 µL/well) is then added and incubated for 10 to 12 minutes at 34-37℃ followed by the addition of Stop Solution (1M Phosphoric acid, 100 uL/well). The stopped plate is then read on a microelisa plate reader at 450 nm against an air blank. For a test to be considered valid, the Negative Control must have an optical density (OD) value of less than 0.100 and the Positive Control must be greater than the Positive Cutoff (pco). The pco is equal to 4X the O.D. value of the Negative Control value. Any specimen with an O.D. value ≥ the pco is considered positive. Any specimen with an O.D. value < the pco is considered negative. Alternatively, the results can be visually read. For this purpose, a visual interpretation card, and written instructions, are provided in the kit for interpretation of results. Any well that produces definite yellow color is considered to be positive.

Here's a breakdown of the acceptance criteria and the study details for the Bartels Legionella Urinary Antigen ELISA Test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to the predicate device's performance, as the study aims to establish substantial equivalence.

Note: The acceptance criteria for the Bartels device would be meeting or exceeding these performance characteristics, particularly in comparison to the predicate device, to demonstrate substantial equivalence. The text explicitly states that "Substantial equivalence was established between the Bartels LUA and the predicate device" and that "there is equivalence between reading the results with an automated plate reader and performing a visual interpretation."

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

• Sample Size (Test Set): 274 clinically well-defined urine specimens.
  • 94 urine specimens from patients whose respiratory specimens were culture-positive for Legionella pneumophila Serogroup 1.
  • 150 urine specimens from patients who did not have a diagnosis of Legionella pneumophila.
  • 30 urine specimens from normal healthy volunteers.
• Data Provenance: The study was performed "at a major infectious disease reference laboratory." The country of origin is not specified but is likely the USA given the FDA 510(k) submission. The data is retrospective, as it uses "clinically well-defined urine specimens" which implies they were collected and characterized prior to the study.

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

• The text does not explicitly state the number of experts used to establish the ground truth.
• Qualifications: The ground truth for positive cases was established by "respiratory specimens were culture-positive for Legionella pneumophila Serogroup 1." This indicates that microbiology experts would have performed these cultures, which is a standard diagnostic method. For negative cases, it's based on "patients who did not have a diagnosis of Legionella pneumophila" and "normal healthy volunteers," implying clinical diagnoses and health assessments.

4. Adjudication Method for the Test Set

• The text does not explicitly state an adjudication method. The ground truth appears to be based on established clinical and laboratory diagnostic methods (culture, absence of diagnosis).

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

• No, a typical MRMC study comparing human readers with and without AI assistance was not performed.
• Instead, a comparison was made for the Bartels LUA ELISA Test itself between two interpretation methods:
  • Automated plate reader.
  • Visual interpretation using a provided card.
• Effect Size: The comparison showed that the visual interpretation had slightly different, but still strong, performance characteristics:
  • Automated Reader: Sensitivity 94.7%, Specificity 91.1%, Accuracy 92.3%
  • Visual Interpretation: Sensitivity 92.6%, Specificity 93.9%, Accuracy 93.4%
  • The conclusion states "there is equivalence between reading the results with an automated plate reader and performing a visual interpretation."

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

• Yes, the performance of the Bartels Legionella Urinary Antigen ELISA Test using an automated plate reader represents a standalone algorithm-only performance. The device provides a quantitative optical density (OD) value, and the cutoff for positive/negative is applied algorithmically (OD value ≥ the pco is considered positive).

7. The Type of Ground Truth Used

• Expert Consensus / Clinical Diagnosis / Pathology:
  • For positive cases: Legionella pneumophila Serogroup 1 culture results from respiratory specimens (considered the "gold standard" as stated in Table 1).
  • For negative cases: Patients "who did not have a diagnosis of Legionella pneumophila" and "normal healthy volunteers." This implies a combined approach of clinical assessment and likely other diagnostic tests (absence of culture results, etc.).

8. The Sample Size for the Training Set

• The text does not mention a separate training set or details on its size. This device is an ELISA test, not a machine learning algorithm in the modern sense. Therefore, it does not typically undergo "training" with a distinct dataset in the way an AI model would. The "design/format" and reagent composition are developed and validated during the product development phase, and the cited clinical study is for performance validation.

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

• As noted above, there isn't a specified "training set" in the context of an AI model. The development of an ELISA test involves extensive research and development to identify appropriate antibodies, optimize concentrations, and establish reaction conditions. The "ground truth" during this development phase would rely on laboratory-derived standards, cultured pathogens, and potentially internal studies with banked clinical samples to refine the assay's components and cutoff values. However, these details are not provided in this 510(k) summary.

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