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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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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.

Not Found

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 Oxoid Dryspot E.coli 0157 test is a latex agglutination test for the identification of E.coli serogroup 0157 in colonies isolated from Sorbitol MacConkey (SMAC) Agar or SMAC Agar with Cefixime Tellurite Supplement. The test is not indicated for direct testing of faccal specimens.

latex agglutination test

This document is a 510(k) clearance letter from the FDA for a medical device, the Oxoid Dryspot E. coli 0157 Kit. It confirms that the device is substantially equivalent to a predicate device and can be marketed. However, this document primarily focuses on regulatory clearance and does not contain the detailed study information needed to describe acceptance criteria and device performance as requested.

Therefore, I cannot provide a complete answer to your request based solely on the provided text. The document does not include:

• A table of acceptance criteria or reported device performance.
• Sample sizes for test sets, data provenance, or details about training sets.
• Information about expert qualifications, adjudication methods, or MRMC studies.
• Details on standalone performance or the type of ground truth used.

To answer your request, I would need access to the actual 510(k) submission document itself, which typically contains the technical and clinical data supporting the substantial equivalence claim. This clearance letter is merely the FDA's decision based on that submission.

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VTEC-RPLA "SEIKEN" is an in vitro diagnostic device for the detection and identification of verotoxic device for in culture isolates of E. coli and is intended as an aid in the diagnosis of Enterohemorrhagic E. coli (EHEC) infections.

VTEC-RPLA "SEIKEN" is a reagent system which can be used for the detection of verotoxins in culture isolates of E. coli to aid in the diagnosis of EHEC infections. It employs antibody-antigen reactions as part of the assay and is based on reversed passive latex agglutination (RPLA). VTEC-RPLA utilizes polyclonal antibodies specific for each verotoxin type, VT1 and VT2, and thus may be used to identify toxins.

This document describes the VTEC-RPLA "SEIKEN" device, an in vitro diagnostic procedure for detecting and identifying verotoxins in E. coli culture isolates to aid in diagnosing Enterohemorrhagic E. coli (EHEC) infections.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Note on Sensitivity: While the VTEC-RPLA "SEIKEN" has a higher minimum detectable concentration (25 pg/well for both VT1 and VT2) compared to the predicate device Premier EHEC (7 pg/well for VT1 and 15 pg/well for VT2), the correlation study still showed 100% sensitivity and specificity when directly comparing both devices with clinical isolates. The FDA's substantial equivalence determination implies that this difference in analytical sensitivity does not compromise clinical performance for the intended use.

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

• Study 1 (in-house, Correlation):
  • Sample Size: 100 Escherichia coli strains (80 verotoxin-producing, 20 non-verotoxin producing).
  • Data Provenance: Obtained from the Japanese National Institute of Infectious Disease. Retrospective (as strains were obtained and then tested).
• Study 2 (external, Correlation):
  • Sample Size: 178 Escherichia coli strains (147 verotoxin-producing, 31 non-verotoxin producing) isolated from humans.
  • Data Provenance: Tested by the Tokyo Metropolitan Research Laboratory of Public Health. Retrospective.
• Sensitivity: 2 verotoxin-producing strains (DK-EC-VT1 and DK-EC-VT2).
• Specificity: 8 verotoxin-producing and 12 non-producing strains of E. coli.
• Reproducibility: Same 2 verotoxin-producing strains as Sensitivity study.
• Dilution: 3 verotoxin-producing strains (DK-EC-PS 1 (VT1), DK-EC- PS 4 (VT2), and DK-EC-PS 7 (VT1 and VT2)).
• Stability: Same 3 reagent lots as Sensitivity study, tested over time.

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 for the test set.

However, for the external correlation study (Study 2), the ground truth for the 178 E. coli strains was established by parallel testing using:

• VTEC-RPLA "SEIKEN"
• PCR (Polymerase Chain Reaction)
• Vero cell assay

The Vero cell assay is a widely accepted method for detecting verotoxicity. PCR is also a molecular method often considered a gold standard for pathogen detection and characterization. The document implies these methods collectively served as the reference for determining whether a strain was "verotoxin-producing" or "non-verotoxin producing."

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for conflicting results if they occurred. However, given that both correlation studies reported 100% sensitivity and 100% specificity for VTEC-RPLA "SEIKEN" compared to the predicate (Study 1) and compared to PCR and Vero cell assay (Study 2), it suggests there were no conflicting results or that discrepancies were resolved in a manner not detailed here. The ground truth seems to be established by the consensus of the reference methods (for Study 2) or the predicate device (for Study 1).

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is an in-vitro diagnostic (IVD) reagent system, not an imaging device or algorithm requiring human interpretation. Therefore, the concept of "human readers improving with AI vs. without AI assistance" is not applicable here.

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

Yes, the studies conducted are essentially standalone performance evaluations of the VTEC-RPLA "SEIKEN" device. It is a laboratory-based assay where the "performance" is the device's ability to detect and identify verotoxins. There is no "human-in-the-loop" component in the sense of an algorithm providing assistance for human interpretation; the device generates a result directly.

7. The Type of Ground Truth Used

• Study 1 (Correlation): The ground truth for the 100 E. coli strains was established by comparison with the Premier EHEC Reagent System, a legally marketed predicate device.
• Study 2 (Correlation): The ground truth for the 178 E. coli strains was established using a combination of PCR and the Vero cell assay. The Vero cell assay can be considered a form of biological activity assay or functional assay, which approximates outcomes data in terms of cellular toxicity, and PCR provides definitive genetic identification of toxin genes.
• Sensitivity, Specificity, Reproducibility, Dilution: The ground truth involved using known verotoxin-producing and non-producing strains, and purified verotoxin preparations with defined concentrations. This is based on established expert classification through prior characterization of these strains and preparations.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI development. This is an in-vitro diagnostic test, not an AI/ML-based device. The studies described are validation and verification studies for its performance.

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

Since there is no "training set" for an AI/ML model, this question is not applicable. The document describes how the reference materials (strains, purified toxins) used in the verification studies were characterized, as outlined in point 7.

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