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The Curian Shiga Toxin assay, for use with the Curian Analyzer, is a rapid, qualitative, fluorescent immunoassay for the simultaneous detection and differentiation of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in a single test device. It is intended for use with cultures derived from human stool specimens to aid in the diagnosis of disease caused by Shiga toxin producing Escherichia coli (STEC) infections. Test results are to be used in conjunction with the patient's clinical symptoms and history.

The Curian® Shiga Toxin assay is a qualitative in vitro diagnostic test for the detection of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in cultures derived from human stool specimens. The Curian® Shiga Toxin assay utilizes fluorescence technology with the cleared Curian® Analyzer (K192817) to detect Stx1 and Stx2 in cultures derived from human stool.

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

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria, but it presents the performance of the Curian Shiga Toxin assay against a reference method (Vero cell Cytotoxin Assay). We can infer the implicit acceptance criteria from the reported performance, which demonstrates high sensitivity and specificity.

Note: The low end of the 95% CI for sensitivity in prospective specimens (e.g., 56.6% for Stx1) is due to the very small number of positive cases in that cohort (5 for Stx1 and 4 for Stx2). The 100% point estimate, while positive, has a wide confidence interval reflecting this small sample size. The archived cohort provides more robust sensitivity estimates.

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

• Prospective Test Set: 1,627 stool specimens collected from patients suspected of having a Shiga toxin-producing Escherichia coli (STEC) infection.
  • Evaluable Prospective Specimens: 1,538
  • Data Provenance: Prospective collection from five clinical study sites representing geographically distinct regions throughout the United States.
• Archived Test Set: 140 archived stool samples.
  • Evaluable Archived Specimens: 135 (5 excluded due to inconclusive reference results).
  • Data Provenance: Retrospective testing of archived samples at all five clinical study sites.

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

The document does not explicitly state the number of experts or their qualifications for establishing the ground truth. It mentions that the reference method was the "Vero cell Cytotoxin Assay (with neutralization) performed on the broth culture obtained from the stool specimen." This is a laboratory-based assay, and its interpretation would typically be performed by trained laboratory personnel rather than a panel of clinical experts (e.g., radiologists).

4. Adjudication Method for the Test Set

The document does not describe any adjudication method for the test set. The ground truth was established by the "Vero cell Cytotoxin Assay (with neutralization)."

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

No, an MRMC comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) assay interpreted by an analyzer, not a medical imaging or diagnostic aid that multiple human readers would interpret with and without AI assistance. The Curian Analyzer automates the interpretation of results ("Results interpretation automated by Curian® Analyzer").

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

Yes, the clinical performance study (both prospective and archived) represents the standalone performance of the device (Curian Shiga Toxin assay and Curian Analyzer). The results are "produced by the Curian Analyzer," indicating an automated, algorithm-only interpretation without a human-in-the-loop performance evaluation in the context of these clinical studies.

7. The Type of Ground Truth Used

The type of ground truth used was a laboratory reference method: the Vero cell Cytotoxin Assay (with neutralization) performed on broth cultures obtained from the stool specimens.

8. The Sample Size for the Training Set

The document does not provide information about the sample size for a training set. This is common for IVD submissions, where the focus is on the analytical and clinical performance of the device itself rather than the development of the underlying algorithms through a specific training set. The device is a "lateral flow fluorescent immunoassay," which is a biochemical detection method, not a machine learning algorithm that typically requires a large training dataset in the same way.

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

Since no training set information is provided, there is no description of how ground truth for a training set was established.

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The SHIGA TOXIN CHEK test is an enzyme immunoassay for the simultaneous qualitative detection of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in a single test. It is intended for use with human fecal samples from patients with gastrointestinal symptoms to aid in the diagnosis of disease caused by Shiga Toxin producing Escherichia coli (STEC). It may be used directly with human fecal specimens, or broth or plate cultures derived from fecal specimens. The test results should be considered in conjunction with the patient history. FOR IN VITRO DIAGNOSTIC USE.

The SHIGA TOXIN CHEK test uses antibodies to Stx1 and Stx2. The microassay wells supplied with the kit contain immobilized monoclonal antibodies against Stx1 and Stx2. The detecting antibody consists of a mixture of anti-Stx1 and anti-Stx2 polyclonal antibodies conjugated to horseradish peroxidase. In the assay, an aliquot of a fecal specimen or culture is emulsified in the Diluent and the diluted specimen is then transferred to the microassay well containing the detecting antibody. If Stx1 and/or Stx2 are present in the specimen, they will bind to the detecting antibody and to the immobilized monoclonal antibodies during the incubation phase. Any unbound material is removed during the washing steps. Following the addition of substrate, a color is detected due to the enzyme-antibody-antigen complexes that form in the presence of toxin.

The SHIGA TOXIN CHEK test is an enzyme immunoassay for the simultaneous qualitative detection of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). It is intended for use with human fecal samples from patients with gastrointestinal symptoms to aid in the diagnosis of disease caused by Shiga Toxin producing Escherichia coli (STEC).

Here's the breakdown of acceptance criteria and the study results:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Clinical Performance - Direct Fecal Testing:

  • Sample Size: 913 samples (899 fresh and 14 frozen specimens).
  • Data Provenance: Not explicitly stated, but clinical performance was evaluated at 3 independent sites, suggesting a mix of retrospective and prospective clinical samples. The origin country is not specified.

• Clinical Performance - Broth Cultures:

  • Sample Size: 789 samples.
  • Data Provenance: Not explicitly stated, but clinical performance was evaluated at 3 independent sites, suggesting a mix of retrospective and prospective clinical samples. The origin country is not specified.

• Reproducibility:

  • Sample Size: 11 fecal specimens (coded to prevent identification).
  • Data Provenance: Tested at 2 independent laboratories and on-site at TECHLAB®, Inc.

• Analytical Sensitivity (LOD):

  • Sample Size: Replicates of 20 for each toxin dilution in a negative fecal pool (direct fecal) or overnight GN broth culture (broth cultures).
  • Data Provenance: Laboratory controlled experiments using highly purified Stx1 and Stx2.

• Analytical Specificity (Cross Reactivity):

  • Sample Size: A panel of various bacterial and viral strains.
  • Data Provenance: Laboratory controlled experiments.

• Precision - Intra-Assay:

  • Sample Size: 6 positive fecal specimens and 6 negative fecal specimens, each assayed in replicates of eight.
  • Data Provenance: Laboratory controlled experiments.

• Precision - Inter-Assay:

  • Sample Size: 12 fecal specimens (six negative, two positive for Stx1, two positive for Stx2, and two positive for both Stx1 and Stx2).
  • Data Provenance: Laboratory controlled experiments.

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 performance studies (Direct Fecal Testing and Broth Cultures) was established using the Vero Cell Cytotoxin Assay with neutralization. This is referred to as the "Clinical Reference Standard (Gold Standard)" in the document.

• Number of Experts: Not specified. The Vero Cell Cytotoxin Assay is a laboratory-based method, and its interpretation would typically be performed by trained laboratory personnel.
• Qualifications of Experts: Not specified. It's implied that trained microbiologists or laboratory technicians would perform and interpret the gold standard assay.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for discrepancies between the SHIGA TOXIN CHEK test and the Vero Cell Cytotoxin Assay. The results provided are direct comparisons. For example, in the direct fecal testing, 78 samples were positive by both methods, 1 was positive by SHIGA TOXIN CHEK and negative by the cytotoxin assay, and 0 were negative by SHIGA TOXIN CHEK and positive by the cytotoxin assay. This suggests that the cytotoxin assay was considered the definitive ground truth, and no further adjudication process is mentioned for conflicting results.

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

This information is not applicable to the SHIGA TOXIN CHEK device. This is an enzyme immunoassay for detecting toxins, not an imaging or diagnostic device that involves human "readers" in the context of interpretation that could be assisted by AI. The device directly produces a qualitative (positive/negative) result based on an enzymatic reaction and color change.

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

The SHIGA TOXIN CHEK is a standalone device in that its performance metrics (sensitivity, specificity, correlation) are reported directly against the gold standard (Vero Cell Cytotoxin Assay) without a human interpretation step that would then be assisted by the device. The device itself performs the detection. The results are read based on a colorimetric reaction, which is then interpreted as positive or negative. The "study" (clinical performance) focuses on the device's accuracy in identifying the presence of the toxins compared to the established gold standard.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical performance studies was the Vero Cell Cytotoxin Assay with neutralization, described as the "Clinical Reference Standard (Gold Standard)".

• For analytical studies (LOD, cross-reactivity, precision), the ground truth was established through controlled laboratory experiments using known concentrations of purified toxins or specific bacterial/viral strains.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is an immunoassay, and its development would typically involve optimization and validation rather than a distinct "training set" for an algorithm. The clinical and analytical studies serve as validation of the device's performance.

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

As there is no explicit "training set" described in the context of an AI/ML model for this immunoassay, this question is not applicable. The ground truth for the validation (test) sets was established using the Vero Cell Cytotoxin Assay with neutralization.

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The SHIGA TOXIN QUIK CHEK test is a rapid membrane enzyme immunoassay for the simultaneous qualitative detection and differentiation of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in a single test device. It is intended for use with human fecal samples from patients with gastrointestinal symptoms to aid in the diagnosis of disease caused by Shiga toxin producing Escherichia coli (STEC). It may be used with fecal specimens, or broth or plate cultures derived from fecal specimens. The test results should be considered in conjunction with the patient history.

FOR IN VITRO DIAGNOSTIC USE.

The SHIGA TOXIN QUIK CHEK test utilizes specific antibodies against Stx1 and Stx2. The Membrane Device contains a Reaction Window with three vertical lines of immobilized antibodies. The "1" test line contains monoclonal antibodies against Stx1. The control line ("C") is a dotted line that contains anti-horseradish peroxidase (HRP) antibodies. The "2" test line contains monoclonal antibodies against Stx2. The Conjugate consists of antibodies to Stx1 and Stx2 coupled to horseradish peroxidase. To perform the test, the sample is added to a tube containing a mixture of Diluent and Conjugate. The diluted sample-coniugate mixture is added to the Sample Well and the device is allowed to incubate at room temperature for 15 minutes. During the incubation, any Stx1 and/or Stx2 present in the sample binds to the antibodyperoxidase conjugates. The toxin-antibody-peroxidase complexes migrate through a filter pad to a membrane where they are captured by the immobilized Stx1 and Stx2 specific monoclonal antibodies in the test lines. The Reaction Window is subsequently washed with Wash Buffer, followed by the addition of Substrate. After a 10 minute incubation period, the Reaction Window is examined visually for the appearance of vertical blue lines on the "1" and "2" sides of the Reaction Window. A blue line on the "1" side of the Reaction Window is a positive result indicating the presence of Stx1. A blue line on the "2" side of the Reaction Window is a positive result indicating the presence of Stx2. A positive "C" reaction, indicated by a vertical dotted blue line under the "C" portion of the Reaction Window, confirms that the test is working properly, the procedure was followed, and the results are valid.

Here's a summary of the acceptance criteria and study details for the SHIGA TOXIN QUIK CHEK device, 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 terms of specific percentages for sensitivity, specificity, and correlation for the clinical performance. Instead, it presents the achieved performance metrics as the outcome of the clinical study. However, the study's findings indicate the device's acceptable performance for its intended use. For the analytical sensitivity, the cutoff points are explicitly defined as the acceptance criteria.

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

• Direct Fecal Testing:
  • Sample Size: 887 specimens (873 fresh, 14 frozen).
  • Data Provenance: Not explicitly stated, but the study was conducted at 3 independent sites, implying clinical samples collected from patients. It does not specify country of origin or whether samples were prospective or retrospective, only that age and sex information was available for 878 patients.
• Broth Cultures Testing:
  • Sample Size: 770 specimens (overnight broth cultures from fecal specimens).
  • Data Provenance: Not explicitly stated, but derived from fecal specimens.

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., number of years of experience).

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for disagreements. The comparison was made against a single "gold standard" reference method.

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

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not mentioned. This device is an in vitro diagnostic device for lab use, not an AI-assisted diagnostic tool for human readers.

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

Yes, the clinical performance study compares the SHIGA TOXIN QUIK CHEK device directly against the gold standard (Vero Cell Cytotoxin Assay), indicating a standalone assessment of the device's performance. The results are based solely on the device's output.

7. The Type of Ground Truth Used

The ground truth used for establishing clinical performance was the Vero Cell Cytotoxin Assay (with neutralization), which is referred to as the "clinical reference standard (gold standard)".

8. The Sample Size for the Training Set

The document describes the device's validation but does not mention a separate "training set" in the context of machine learning or AI models. This is an in vitro diagnostic test, and its development typically involves internal analytical studies rather than a distinct training/test set split as seen in AI algorithms.

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

As there's no mention of a "training set" for an AI model, this question is not applicable in the context of this traditional in vitro diagnostic device. The device's analytical setup (e.g., cutoff points for LOD) was established empirically using purified toxins and negative fecal/broth pools, following established protocols (EP17A).

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The BioStar® OIA® SHIGATOX assay is an Optical Immunoassay (OIA) test for the qualitative, rapid detection of the presence of Shiga toxins in human diarrheal fecal specimens, broth cultures, fecal specimens in Cary Blair Transport Media, or swab sampling of colonies from a culture plate. This test is intended for in vitro diaqnostic use as an aid in the diagnosis of infection by Shiga toxin-producing Escherichia coli (STEC) both O157 and all non - O157 Shiga toxin-producing strains.

The OIA SHIGATOX test involves the qualitative detection of Shiga toxins 1 and 2 (Stx1 and Stx 2) produced by certain strains of Escherichia coli and other organisms. The Optical ImmunoAssay technology enables the direct visual detection of a physical change in the optical thickness of molecular thin films. This change is the result of antigen - antibody binding on an optical surface (silicon wafer). After a specimen potentially containing Shiga toxin is mixed with conjugates and placed directly on the optical surface, the immobilized surface antibodies capture the antigen/conjugate complex. After washing, the substrate is added, increasing the thickness (mass enhancement) of the molecular thin film. This change in thickness alters the reflected light path, and this alteration is visually perceived as a color change. Slight changes in the optical thickness produce a distinct visible color change. A positive result appears as a purple spot on the gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged, and the surface retains the original gold color indicating a negative result.

More specifically, the BioStar OIA SHIGATOX device is based on a novel thin film optical detection technology that relies on the interaction of white light with thin films to create a destructive interference phenomenon. Characteristic of this phenomenon is the generation of a reflective surface that changes color as a function of the change in optical thickness (refractive index x thickness) of the films on the surface of the device. To take advantage of this phenomenon for monitoring biological binding events, the optical surface with a special background color is coated with a capture reagent specific to the analyte of interest. In the OIA SHIGATOX device, the biological capture film is a combination of affinity-purified polyclonal antibodies to Shiga toxins 1 and 2 (Stx 1 and Stx 2). Samples suspected of containing either or both of the toxins are mixed with cocktail containing polyclonal antibodies to Stx 1 and Stx 2 that have been covalently conjugated to horseradish peroxidase (HRP). Once a sample containing toxins or either toxin is applied to the surface, the immune complex of toxin(s) and the anti-toxin-HRP conjugate(s) are bound to the surface antibodies. Following a wash step, a precipitating substrate for HRP is added, and a thin film generated by the immobilized immune complex is enhanced by the precipitation of the HRP product. Once washed and dried, a simple color change relative to the gold background color is observed as an indication of the presence of Stx 1 or Stx 2 in the original specimen.

The OIA SHIGATOX device produces a qualitative result for the presence or absence of Shiga toxin as the device output. Input to the device is the simple addition of an aliquot of fecal material (direct or in transport media) or broth culture to the reagents contained in the kit. Fecal samples are routinely collected and no special collection requirements exist. Test devices within the kit are single use devices, and disposal instructions are provided in the Package Insert. The kit contains all components necessary for analysis of the range of samples approved for use in this product, with the exception of a timer.

Here's a summary of the acceptance criteria and study details for the BioStar® OIA® SHIGATOX device based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for each study type are implicitly defined by the reported performance, which consistently achieved high accuracy. For the analytical studies, the key criteria were demonstrating sensitivity and specificity, and the reproducibility studies aimed for 100% agreement. For clinical studies, the percentage agreements with comparator methods (EIA, SMAC, CTA, or reference OIA) were the primary metrics.

Study Details:

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

   • Analytical Sensitivity: No specific sample size for a "test set" in the traditional sense, but tested in triplicate for LOD determination (5 samples at each concentration analyzed on 2 lots of devices).
   • Analytical Strain Recognition: 70 clinical isolates (49 from a Department of Public Health, 21 from a university laboratory) + Shigella dysenteriae (ATCC 13313). Data provenance appears to be from US public health and university laboratories.
   • Analytical Specificity (Cross-Reactivity): 43 different organisms and Rotavirus-positive stools.
   • Reproducibility Studies: 9 sample types (Negative, Low Stx 1, Low Stx 2, Moderate Stx 1, Moderate Stx 2, various combinations). Each sample tested in triplicate by each of 6 operators over 3 consecutive days for a total of 486 tests (9 samples * 3 replicates * 6 operators * 3 days). Data provenance: Not explicitly stated beyond "clinical trial sites" and "Physician Office Laboratories (POL) sites." Samples were prepared by spiking stools from a healthy individual.
   • Clinical Specimen Testing (Unmodified Device):
     • Colony Sweep: 21 positive samples (from 22 frozen fecal specimens, one failed to grow). Data provenance: Not explicitly stated, samples were "previously found to contain Shiga toxin producing E. coli."
     • Direct Stool (Prospective): 272 prospective diarrheal fecal specimens. Data provenance: Collected from three clinical trial sites in the Eastern and Western regions of the United States.
     • Direct Stool (Frozen): 62 additional frozen specimens. Data provenance: Not explicitly stated, but "two of the clinical sites" performed this study.
     • Broth Culture (Fresh): 269 prospective diarrheal fecal specimens (from original 272, three failed to grow). Data provenance: Same as Direct Stool (Prospective).
     • Broth Culture (Frozen): 50 frozen specimens (from 62, 12 were not tested or failed to grow). Data provenance: Same as Direct Stool (Frozen).
     • SMAC Culture Comparison (Fresh Stool): 269 direct stool samples. Data provenance: Same as Direct Stool (Prospective).
     • SMAC Culture Comparison (Frozen Stool): 62 frozen samples. Data provenance: "two of the clinical sites."
     • CTA Comparison: 19 specimens (direct stool aliquot and broth culture aliquot) from the clinical study (one excluded as inconclusive).
   • Clinical Specimen Testing (Modified Device - New Sample Types):
     • Cary Blair & Broth Inoculation Validation: 98 frozen fecal specimens. Data provenance: Collected from 2 laboratory sites (University of Utah & Primary Children's, Fairfax Hospital).
     • 1 and 24 Hour Cary Blair (vs. Direct OIA): 98 frozen fecal specimens.
     • GN/MAC Broth Culture (Direct Fecal vs. MAC Broth OIA): 98 fecal specimens.
     • GN Broth from Cary Blair (vs. Direct MAC Broth OIA): 98 fecal specimens.
     • MAC Broth from Cary Blair (vs. Direct MAC Broth OIA): 98 fecal specimens.

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

   • Analytical Strain Recognition: Ground truth based on "previously analyzed for the presence of Shiga toxin genes and serotyped" by the Department of Public Health and a university laboratory. No specific number or qualifications of experts are given, but implies laboratory expertise in molecular and serological typing.

   • Clinical Studies (Unmodified Device):

     • Comparator Methods: A commercial EIA test, SMAC culture, and Cytotoxicity Testing Assay (CTA) were used as comparators or ground truth methods.
     • CTA Confirmation: "All positive results from either immunoassay method were confirmed by cytotoxicity testing, CTA." CTA itself is a reference method for Shiga toxin activity. No specific number or qualifications of "experts" involved in CTA interpretation are provided, but it's an established laboratory method.
     • Clinical sites were staffed by MT ASCP (Medical Technologists certified by the American Society for Clinical Pathology).

   • Reproducibility Studies: Expected results were based on the known spiked concentrations of toxins.

   • Clinical Studies (Modified Device): Direct fecal testing in the OIA method or direct fecal inoculation of MAC broth were used as reference methods.

3. Adjudication method for the test set:

   • For the prospective clinical studies, "All positive results from either immunoassay method were confirmed by cytotoxicity testing, CTA." This implies a form of adjudication where discrepant positive immunoassay results were further investigated by CTA, serving as a higher-level reference.
   • For reproducibility studies, there was no adjudication method mentioned, as results were compared to known spiked concentrations.

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 is not an AI-assisted device. The device is a rapid diagnostic test (Optical Immunoassay) for direct detection of Shiga toxins, generating a visible color change for interpretation. Therefore, an MRMC comparative effectiveness study comparing human readers with and without AI assistance is not applicable.
   • The "Reproducibility Studies" did involve multiple operators (6 operators across 6 sites) reading 27 blinded and randomized samples in triplicate over 3 days, demonstrating consistency in human interpretation of the device's visual output. This is a multi-reader, multi-case study for reproducibility, but not for AI-assisted human improvement.

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

   • Yes, the performance data presented (e.g., sensitivity, specificity, agreement percentages) is the standalone performance of the OIA SHIGATOX device. The device produces a "qualitative result for the presence or absence of Shiga toxin as the device output" based on a visual color change. While a human interprets this visual change, the performance metrics reported represent the device's ability to correctly identify the toxin compared to reference methods, independent of human variability in the interpretation step. The high reproducibility across multiple readers attests to the clarity and consistency of this visual output for human interpretation.

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

   • Analytical Strain Recognition: Shiga toxin gene presence and serotyping (presumably by molecular and serological methods).
   • Clinical Studies (Unmodified Device):
     • Primary Comparator: Commercial EIA test.
     • Confirmatory Reference: Cytotoxicity Testing Assay (CTA).
     • Additional Comparator: SMAC culture (acknowledged for its limitations as a direct comparison method for all STEC).
   • Clinical Studies (Modified Device):
     • Primary Reference: Direct fecal testing in the OIA method (for Cary Blair comparisons) or direct fecal inoculation of MAC broth (for broth culture comparisons). These are essentially using the device itself or a similar culture method as the internal reference for evaluating new sample types with the device.

7. The sample size for the training set:

   • The document does not explicitly describe a "training set" in the context of a machine learning algorithm. This is a medical device (Optical Immunoassay), not an AI/ML algorithm. The development process involved various analytical studies and clinical trials to establish performance, but these are not referred to as "training sets." The 70 clinical isolates used for Analytical Strain Recognition and the samples used for analytical sensitivity and specificity contribute to establishing the device's operational characteristics, which is analogous to a development set in traditional terms.

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

   • As noted above, there isn't a "training set" in the context of an AI/ML device. However, the ground truth for the various analytical and clinical studies were established using methods such as:
     • Known spiked concentrations of purified Stx 1 and Stx 2 toxins (for analytical sensitivity).
     • Clinical isolates "previously analyzed for the presence of Shiga toxin genes and serotyped" (for analytical strain recognition).
     • Reference tests like commercial EIA, SMAC culture, and crucially, Cytotoxicity Testing Assay (CTA) for clinical samples (for general device performance validation).

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ImmunoCard STAT! EHEC is an immunochromatographic rapid test for the qualitative detection of Shiga toxins 1 and 2 (also called Verotoxins) produced by E. coli in cultures derived from clinical stool specimens. ImmunoCard STAT! EHEC is used in conjunction with the patient's clinical symptoms and other laboratory tests to aid in the diagnosis of diseases caused by enterohemorrhagic E. coli (EHEC) infections.

ImmunoCard STAT! EHEC is an immunochromatographic rapid test utilizing monoclonal antibodies labeled with red-colored gold particles. The test device has a circular sample port and an oval-shaped test (Toxin 1, Toxin 2) and control (Control) window. The sample is applied to the chromatography paper via the circular sample port. The sample is absorbed through the pad to the reaction zone containing colloidal, gold-labeled antibodies specific to Shiga toxins. Any Shiga toxin (ST1 and ST2) antigen present complexes with the gold-labeled antibody and migrates through the pad until it encounters the binding zones in the test (Toxin 1, Toxin 2) area. The binding zones (Toxin 1 and Toxin 2) contain another anti-ST1 or -ST2 antibody, which immobilizes any Shiga toxin-antibody complex present. Due to the gold labeling, a distinct red line is then formed. The remainder of the sample continues to migrate to another binding reagent zone within the control zone, and also forms a further distinct red line (positive control). Regardless of whether any Shiga toxin is present or not, a distinct red line should always be formed in the control zone and confirms that the test is working correctly.

Here's a summary of the acceptance criteria and study details for the ImmunoCard STAT! EHEC device, based on the provided text:

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the comparative performance against the predicate device, Premier EHEC, and the Duopath Verotoxin GLISA, as well as the observed reproducibility. The document emphasizes "substantial equivalence" as the primary goal. The critical performance metrics are clinical sensitivity and specificity.

Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria in a dedicated section. Instead, the "Substantial Equivalence" determination (K062546) is based on the performance of the new device being comparable to the predicate device and being safe and effective for its intended use. The predicate device's performance characteristics serve as the benchmark for "acceptable" performance. The post-resolution values for sensitivity and correlation are higher and demonstrate improved agreement with the gold standard.

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

• Test Set Sample Size: A total of 360 stool samples were evaluated (340 produced growth in GN broth, 344 in Mac broth).
• Data Provenance: The data was collected from clinical samples in the United States, Canada, and Argentina. The study was prospective for collecting clinical samples to validate the product's new intended use with broth cultures. Some samples were tested fresh, while others were evaluated following frozen storage.

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 or qualifications of experts used to establish the ground truth. It refers to the cytotoxin assay (CTA) as the method for resolving discrepant results, which implies a laboratory-based gold standard.

4. Adjudication Method for the Test Set

• Adjudication Method: Discrepant results between the ImmunoCard STAT! EHEC and the predicate device (Premier EHEC) were further analyzed using a cytotoxin assay (CTA). This indicates an adjudication process where the CTA served as a tie-breaker or definitive test for discordant outcomes.

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

• No, an MRMC comparative effectiveness study was not explicitly mentioned or described in the provided text. The device is a rapid immunochromatographic assay with clear positive/negative results (red lines), which typically does not involve human interpretation variability in the same way as imaging studies. The performance metrics focus on the device's accuracy against a reference standard.

6. If a Standalone Study Was Done

• Yes, a standalone study was performed. The "Performance evaluation" section details the evaluation of ImmunoCard STAT! EHEC with clinical samples (broth cultures) and its performance (sensitivity, specificity) was measured independently and then compared to the predicate device.

7. The Type of Ground Truth Used

• Primary Ground Truth: The predicate device (Premier EHEC) was initially used as the reference for comparison in calculating initial sensitivity and specificity. However, for resolving discrepant results, the cytotoxin assay (CTA) was used, which represents a more definitive diagnostic method for Shiga toxins. Therefore, the ground truth for discordant samples was cytotoxin assay (outcomes data/definitive lab test).

8. The Sample Size for the Training Set

• The document does not specify a separate training set size. The study focuses on the performance evaluation of the ImmunoCard STAT! EHEC for its new intended use. Since this is an immunochromatographic assay, typically, extensive machine learning training sets in the modern sense are not applicable. The device's design and reagent selection would have been developed prior to this validation study.

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

• As no explicit training set is mentioned in the context of machine learning, this question is not applicable in the traditional sense. The "ground truth" for the device's development (e.g., antibody selection, assay parameters) would have been established through a combination of scientific knowledge, laboratory experiments with known positive and negative controls, and optimization trials, rather than a single "training set" with established ground truth from clinical samples.

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The BioStar® OIA® SHIGATOX assay is an Optical Immunoassay (OIA) test for the qualitative, rapid detection of the presence of Shiga Toxins in human diarrheal fecal specimens, broth cultures, and swab sampling of colonies from a culture plate. This test is intended for in vitro diagnostic use as an aid in the diagnosis of infection by Shiga Toxinproducing Escherichia coli (STEC), both 0157 and all non -- 0157 Shiga toxin producing strains.

The BioStar OIA SHIGATOX device is based on a novel thin film optical detection technology that relies on the interaction of white light with thin films to create a destructive interference phenomenon. Characteristic of this phenomenon is the generation of a reflective surface that changes color as a function of the change in optical thickness (refractive index x thickness) of the films on the surface of the device. To take advantage of this phenomenon for monitoring biological binding events, the optical surface with a special background color is coated with a capture reagent specific to the analyte of interest. In the OIA SHIGATOX device, the biological capture film is a combination of affinity-purified polyclonal antibodies to Shiga toxins 1 and 2 (Stx 1 and Stx 2). Samples suspected of containing either or both of the toxins are mixed with cocktail containing polyclonal antibodies to Stx 1 and Stx 2 that have been covalently conjugated to horseradish peroxidase (HRP). Once a sample containing toxins or either toxin is applied to the surface, the immune complex of toxin(s) and the anti-toxin-HRP conjugate(s) are bound to the surface antibodies. Following a wash step, a precipitating substrate for HRP is added, and a thin film generated by the immobilized immune complex is enhanced by the precipitation of the HRP product. Once washed and dried, a simple color change relative to the gold background color is observed as an indication of the presence of Stx 1 or Stx 2 in the original specimen.

The OIA SHIGATOX device produces a qualitative result for the presence or absence of Shiga toxin as the device output. Input to the device is the simple addition of an aliquot of fecal material or broth culture to the reagents contained in the kit. Fecal samples are routinely collected, and no special collection requirements exist beyond the elimination of the use of fecal transport media. Test devices within the kit are single use devices, and disposal instructions are provided in the Package Insert. The kit contains all components necessary for analysis of the direct stool sample with the exception of a timer.

Here's a breakdown of the acceptance criteria and the study details for the BioStar® OIA® SHIGATOX device based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state numerical "acceptance criteria" against which the device performance was measured in the same way a clinical trial might define primary endpoints. Instead, it presents the performance of the device and claims substantial equivalence to predicate devices. For this table, I've extracted the performance metrics reported for the OIA SHIGATOX device from the clinical testing summaries and listed them alongside the performance of the predicate device for comparison, as this is how the document frames its "acceptance." The "acceptance criteria" here are implied by the performance of the predicate devices the OIA SHIGATOX device aims to be equivalent to.

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

• Clinical Sensitivity and Specificity (Direct Stool): 272 prospective specimens from diarrheal patients.
• Clinical Sensitivity and Specificity (Frozen Direct Stools): 62 additional frozen specimens (prospectively tested).
• Broth Culture (Fresh Stools): 269 prospective specimens from diarrheal patients (3 failed to produce growth, so 266 used for comparison).
• Broth Culture (Frozen Stools): Insufficient data, described as "ten of the frozen specimens were not tested" and "Two of the remaining specimens failed to exhibit growth," implying a small subset of the 62 frozen specimens. The exact number used in the comparison table is not explicitly stated.
• SMAC Culture (Direct Fresh Stool): 269 direct stool samples.
• SMAC Culture (Frozen Stool): 62 frozen specimens.
• Reproducibility: A panel of 27 fecal specimens.
• Toxigenic Strain Testing: 49 isolate strains from a Department of Public Health, 21 isolate strains from a university laboratory, or other commercial source (total 70 isolates).
• Analytical Specificity (Cross Reactivity): 49 bacteria species, Cryptosporidium, Giardia, Candida albicans.
• Interfering Substances: Multiple tests on samples containing Barium Sulfate, Bovine Mucin, Kaopectate, Pepto Bismol, Imodium®, and Whole Blood (tested in duplicate), with and without toxin spikes.

Data Provenance:

• Clinical Studies: Conducted at three clinical trial sites in the Eastern, Southern, and Western regions of the United States.
• Toxigenic Strain Testing: Clinical isolates obtained from a Department of Public Health and a university laboratory, or other commercial source.
• The data appears to be a mix of prospective (for direct stool and broth culture comparisons) and retrospective/archival (for frozen direct stools and toxigenic strain testing).

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

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

• Ground truth for clinical performance was primarily established by:
  • Commercial EIA tests (predicate devices).
  • Cytotoxicity Testing Assay (CTA) as the confirmatory method for positive immunoassay results.
  • SMAC culture (Sorbitol MacConkey plates) for E. coli O157.
• For the toxigenic strain testing, the isolates were "previously analyzed for the presence of Shiga toxin genes and serotyped," implying some form of expert confirmation, but specifics are missing.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 expert review) for the test set.

• The primary method for confirming positive immunoassay results was Cytotoxicity Testing Assay (CTA). "All positive results from either immunoassay method were confirmed by cytotoxicity testing."

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

No, a MRMC comparative effectiveness study was not explicitly stated or performed. This device is an in vitro diagnostic test that produces a qualitative result (positive/negative), not an imaging device or AI algorithm designed to assist human readers. The clinical studies compare its performance to other in vitro diagnostic methods (EIA, SMAC, CTA), not to human reader performance with or without AI assistance.

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

The BioStar® OIA® SHIGATOX device is a standalone diagnostic test. It functions as an "algorithm only" in the sense that the device itself, through its chemical and optical reactions, generates a result without direct human interpretation influencing the test outcome beyond visually observing a color change (a "purple spot on the gold background" for positive, "original gold color" for negative). The "human-in-the-loop" component is simply reading the device's output, not interpreting complex data or making a diagnosis with AI assistance.

7. The Type of Ground Truth Used

The types of ground truth used are:

• Predicate Device Performance: Performance of legally marketed EIA tests (Premier EHEC and ProSpecT® Shiga Toxin Microplate Assay).
• Cytotoxicity Testing Assay (CTA): Considered the confirmatory reference method for Shiga toxins.
• SMAC Culture (Sorbitol MacConkey agar): Used specifically for the determination of E. coli O157.
• Molecular/Serological Characterization: For toxigenic strains, they were "previously analyzed for the presence of Shiga toxin genes and serotyped."

8. The Sample Size for the Training Set

The document does not provide information on a specific "training set" as this is an in vitro diagnostic device, not a machine learning model. The various analytical studies (analytical sensitivity, specificity, interfering substances) and the development process itself would have involved testing and refinement, but these are not referred to as a "training set" in the context of AI/ML.

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

Since there is no explicit "training set" for an AI/ML model, this question is not applicable in the context of this device and report. The analytical performance (sensitivity, specificity, strain recognition) was established through controlled laboratory experiments using purified toxins, characterized bacterial strains, and spiked stool samples.

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The Duopath® Verotoxins GLISA test is a rapid test for the qualitative identification of verotoxins Fand if (Onlya like toking) produced by E. coli isolated in cultures derived promotion aids in the diagnosis of diseases caused by enterohemorrhagic E. coli infections.

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The provided document is a 510(k) clearance letter from the FDA for the Duopath® Verotoxins GLISA test. This type of document primarily confirms that a new medical device is "substantially equivalent" to a legally marketed predicate device, meaning it has the same intended use and technological characteristics (or different ones that do not raise new questions of safety or effectiveness).

Crucially, this document does not contain the detailed study results, acceptance criteria, or performance data that would typically be found in a full submission with clinical or analytical performance studies. The clearance letter references the 510(k) submission (K031367) which would contain this information, but the submission itself is not provided here.

Therefore, many of the requested details cannot be extracted from the given text.

Here's what can be inferred and what cannot be provided:

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

• Cannot provide. The document states "We have reviewed your Section 510(k) premarket notification... and have determined the device is substantially equivalent...". This implies that the FDA's acceptance criteria for substantial equivalence were met, and the performance data within the submission supported this. However, the specific quantitative acceptance criteria (e.g., sensitivity, specificity thresholds) and the reported performance values are not present in this letter.

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

• Cannot provide. This information would be found in the detailed study report within the 510(k) submission, not in the clearance letter.

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)

• Cannot provide. This information is not typically part of the FDA clearance letter, but rather in the study design documentation. For an in vitro diagnostic like this, the "ground truth" often comes from a reference culture method or a highly characterized strain rather than human expert interpretation of images.

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

• Cannot provide. Adjudication methods are relevant for studies where human interpretation of results has variability, especially in imaging. For a GLISA test (an immunoassay), the "ground truth" is typically established via laboratory methods, not expert adjudication in the same sense as an imaging study.

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 / Cannot provide. MRMC studies are specific to imaging devices where human readers interpret medical images, sometimes aided by AI. The Duopath® Verotoxins GLISA test is an in vitro diagnostic test, not an imaging device, and does not involve AI assistance for human image interpretation. Therefore, an MRMC study or AI assistance effect size is not relevant to this device.

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

• Not applicable / Cannot provide. As an in vitro diagnostic test, the "algorithm only" concept (as it pertains to AI/software) doesn't directly apply. The GLISA test is a standalone diagnostic kit with a defined protocol and reagents. Its performance is evaluated on its ability to detect specific analytes. Whether the interpretation of that test involves a human 'in the loop' is a separate question, but not in the same sense as an AI algorithm processing data.

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

• Inferred based on device type: For an in vitro diagnostic test like the Duopath® Verotoxins GLISA, the most common type of ground truth would be reference culture methods, PCR, or highly characterized bacterial strains known to produce (or not produce) Verotoxins. This would be established by microbiological laboratory techniques, not expert consensus or pathology in the clinical sense. The specific methodology would be detailed in the 510(k) submission.

8. The sample size for the training set

• Not applicable / Cannot provide. This device is an in vitro diagnostic kit, not a machine learning or AI model that requires a "training set" in the computational sense. Its design and validation rely on analytical studies (e.g., specificity, sensitivity, cross-reactivity) using known samples, not on a machine learning training paradigm.

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

• Not applicable / Cannot provide. (See point 8).

In Summary:

The provided document is a regulatory clearance letter. It confirms the FDA's determination of substantial equivalence for the Duopath® Verotoxins GLISA test. It does not include the detailed performance study results, acceptance criteria, sample sizes, or methodologies for ground truth establishment, which would be part of the full 510(k) submission.

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The ImmunoCard STAT! E.coli O157 Plus is a rapid test for the detection of antigens from shiga toxin producing E.coli O157 as an aid in the diagnosis of E.coli O157:H7 infection. The test can be used to directly test stool specimens, stool in modified Cary-Blair medium or confirmatory stool cultures grown in MacConkey broth or sorbitol MacConkey (SMAC) plates.

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The provided text is a 510(k) clearance letter from the FDA for the "ImmunoCard STAT! E.coli 0157 Plus" device. It does not contain information regarding
acceptance criteria, study design, sample sizes, expert qualifications, or ground truth
details. Therefore, I cannot provide the requested information based on the input text.

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The Immunocard STAT! STEC O157 is a rapid test for the detection of antigens from shiga toxin producing E. coli O157 as an aid in the diagnosis of E. coli O157:H7 infection. The test can be used to directly test stool specimens, or confirmatory stool cultures grown in MacConkey broth or sorbitol MacConkey (SMAC) plates.

Stool or culture material are prepared / diluted and added to the sample port of the device. The sample mobilizes gold particles, coated with monoclonal antibody specific for the O157 lipopolysacchride, and migrates along the membrane through the Test and Control zones. The test zone contains immobilized monoclodal antibody specific for an epitope common to shiga toxin producing E. coli. After ten minutes the Test and Control zones are observed for the presence of red/purple lines across the membrane surface. If a shiga toxin producing E. coli O157 is present in the sample, a complex is formed between the capture antibody, the shiga toxin producing E. coli O157, and the monoclonal antibody-gold conjugate which can be seen visually as a red/purple line in the Test zone. No red/purple line in the Test zone indicates a negative result. The Control line serves as a procedural control, to assure that the sample has migrated the appropriate distance along the membrane.

This document describes the ImmunoCard STAT! STEC O157 device, a rapid test for detecting E. coli O157 antigens.

Here's an analysis of its acceptance criteria and the study performance:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for the ImmunoCard STAT! STEC O157. However, it presents the performance of the device in comparison to a predicate device (E. coli O157 Elisa Stool Assay), which implies these performance metrics are considered acceptable for market clearance. The key performance metrics are Sensitivity and Specificity for stool samples.

Note: The document also lists performance for the predicate device across various sample types including formalinized stool, MacConkey broth, and SMAC plates (100% Sensitivity, 99-100% Specificity), but these are for the predicate and not the ImmunoCard explicitly across all those sample types in the summary table.

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

• Sample Size: The document does not explicitly state the sample size used for the clinical test set evaluating the ImmunoCard STAT! STEC O157.
• Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It only mentions "patient stool" in the intended use and comparison tables.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

The document does not provide information on the number of experts used or their qualifications for establishing the ground truth of the test set.

4. Adjudication Method for the Test Set:

The document does not describe any adjudication method (e.g., 2+1, 3+1, none) used for the test set.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is a manual, visually read lateral flow immunoassay. Its interpretation is straightforward (presence or absence of a line). Therefore, a study focusing on inter-reader variability or the improvement of human readers with AI assistance would not be applicable.

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

Yes, the study primarily describes the standalone performance of the device. The ImmunoCard STAT! STEC O157 is a rapid test that provides a visual reading (red/purple line) after ten minutes, interpreted by a laboratory technician without any algorithmic or AI involvement. The reported sensitivity and specificity are for this standalone operation.

7. Type of Ground Truth Used:

The document doesn't explicitly state the exact "ground truth" method used for the clinical study. However, given that it's a diagnostic test for E. coli O157 and the comparison to "culture" is mentioned (in the statement "The safety and effectiveness of both assays are both substantially equivalent when compared to culture"), it is highly probable that bacteriological culture was used as the gold standard for confirming the presence or absence of E. coli O157 in patient stool samples.

8. Sample Size for the Training Set:

The document does not provide information on a "training set" sample size. This type of device (lateral flow immunoassay) typically does not involve machine learning algorithms that require a distinct training set. Its development involves optimizing chemical and biological components, not training a model on data in the conventional sense.

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

As there is no mention of a training set for a machine learning model, there is no information on how its ground truth was established. The development of such a diagnostic test relies on fundamental microbiology, immunology, and chemistry principles, not data-driven model training.

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