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The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene is a PCR instrument that automates lysis and dilution of samples, followed by nucleic acid amplification, and detection of target sequences by fluorescence-based real-time PCR. Revogene runs are orchestrated by a combination of software, firmware and instrument control protocol that ensures the adequate combination times and temperatures for sample homogenization and PCR analysis. The Revogene instrument acquires fluorescence signals generated during amplification. The signals are then interpreted by the system using embedded calculation algorithms.

The Revogene requires the use of a 'PIE', i.e., an assay-specific cartridge to which a patient sample is added. The PIE contains the reagents needed to process a sample and to perform a PCR amplification. When the number of assay PIEs to be run is lower than eight, the user fills empty spaces with "MOCK PIE", which are cartridges that simulate the presence of an assay PIE to confer thermal and rotational balance.

The Revogene instrument subject of this Premarket Notification is substantially equivalent to the Revogene instrument cleared under K222779. Meridian is submitting this 510(k) Premarket Notification to implement a photomultiplier tube (PMT) cooling system. This cooling system keeps the PMT environment at a temperature that prevents the appearance of fluorescence glitches, which may stop the Revogene instrument

The provided document is a 510(k) Premarket Notification for a modified medical device, the Revogene instrument. It focuses on the changes made to an existing device (K222779) and its substantial equivalence to the predicate device.

The document does not contain information about acceptance criteria or a detailed study proving the device meets specific acceptance criteria, as one might find in a clinical trial report for an initial device clearance.

Instead, it describes the performance characteristics of functional testing conducted to demonstrate that the modifications (PMT cooling system and Windows 10 upgrade) do not adversely affect the device's performance compared to the predicate. The goal of this submission is to show substantial equivalence, not to establish new performance acceptance criteria.

Therefore, I cannot provide a table of acceptance criteria and reported device performance in the traditional sense, nor can I answer many of your specific questions about study design, sample sizes, ground truth establishment, or expert adjudication, as this information is not present in the provided text.

However, I can extract the available information regarding the functional testing that was performed to support the substantial equivalence claim.

Summary of Available Information on Device Performance and Testing:

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

The document does not explicitly state quantitative acceptance criteria. Instead, it describes general observations and conclusions from functional testing. The implicit acceptance criterion is "no statistically significant differences" and "operates as expected and yields expected assay results."

2. Sample size used for the test set and the data provenance

• Sample Size for Test Set: The document states "contrived and negative samples in relevant clinical matrix using the following assays...". However, it does not specify the number of samples or runs used for this functional testing.
• Data Provenance: Not explicitly stated, but given it's a regulatory submission by a US company, the testing would typically be conducted according to established protocols within their R&D or QA departments. It is retrospective relative to the design changes, but the testing itself is performed to support the new device version. No information on country of origin of data beyond the manufacturer's location.

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

• This information is not provided as the testing described is functional performance testing of the instrument, not typically involving expert interpretation of patient samples for ground truth establishment. The "ground truth" here is the expected performance of control samples within the assays.

4. Adjudication method for the test set

• This is not applicable/provided. The testing focuses on the instrument's functional output (e.g., Ct values, glitch occurrence) rather than interpretation of results that would require adjudication.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

• No, this was not done. The device is an instrumentation for clinical multiplex test systems, meaning it processes samples and detects nucleic acids. It does not output images or data that require human readers for interpretation in the way an AI diagnostic imaging device would. Therefore, an MRMC study is not relevant to this type of device or its modifications.

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

• The device itself is a standalone instrument that performs automated lysis, dilution, amplification, and detection. The "algorithm" here refers to the embedded calculation algorithms within the system that interpret fluorescence signals to determine results. The functional testing described is a form of standalone performance evaluation for the modified instrument. There is no human-in-the-loop component mentioned for the actual nucleic acid detection and interpretation process of the instrument.

7. The type of ground truth used

• The ground truth for the functional testing appears to be based on the expected outcomes from known contrived and negative samples when run with specific IVD assays (Revogene® Strep A, Revogene® Carba C and Revogene® SARS-CoV-2). Essentially, the "ground truth" is the established performance of the assays themselves on control materials, and the instrument must correctly process these, showing no statistical degradation from the predicate.

8. The sample size for the training set

• This information is not provided and is generally not applicable in the context of hardware modifications to an existing IVD instrument as described. The "training set" concept is typically relevant for machine learning algorithms, which are not detailed here beyond "embedded calculation algorithms" that likely leverage established PCR physics and signal processing rather than iterative machine learning training.

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

• This information is not provided as there is no mention of a traditional "training set" in the machine learning sense. The established performance of the assays with known control materials serves as the reference for evaluating the modified instrument.

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The Premier HpSA Flex enzyme immunoasay (EIA) is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. The test is intended for use with unpreserved stool specimens or preserved stool specimens in transport media. Test results are intended to aid in the diagnosis of H. pylori infection and to monitor response during and post- therapy in patients. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least four weeks following completion of therapy.

Meridian Bioscience has modified its FDA-cleared PREMIER Platinum HpSA® PLUS assay (K182559), a qualitative, in vitro diagnostic test for the detection of Helicobacter pylori antigens present in unpreserved human stool specimens. This modification, to be marketed under new device trade name Premier HpSA® Flex upon FDA clearance, is the addition of a new specimen type claim to the intended use of the previously cleared device (K182559) whereby specimens may be preserved in Cary-Blair or Culture and Sensitivity (C&S) transport media.

The Premier HpSA Flex test is a microwell-based enzyme immunoassay that detects H. pylori antigens present in human stool specimens, either unpreserved in transport media. The test uilizes a plurality (mixture) of monoclonal anti-H. pylori capture antibodies adsorbed to microwells. Diluted patient samples and an enzyme conjugate reagent are added to the microwells and incubated for one hour at room temperature. A wash is performed to remove unbound material. Substrate is added and incubated for 10 minutes at room temperature. Color develops in the presence of bound enzyme. Stop solution is added and the results are interpreted visually or spectrophotometrically.

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

Acceptance Criteria and Device Performance

The core of this submission is about adding a new specimen type claim (preserved stool in Cary-Blair or C&S transport media) to an already FDA-cleared device. Therefore, the "acceptance criteria" revolve around demonstrating that the device performs equivalently with these new specimen types as it did with the original unpreserved stool and that the performance remains robust.

Here's a summary of the performance characteristics presented as implicit acceptance criteria and the reported device performance:

Study Details

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

   • Analytical Sensitivity (LoD): Not explicitly stated how many samples per lot were used in the LoD study, but it mentions "Three lots" and "positive results >= 95% of the time."
   • Precision/Reproducibility: 360 samples (10 panels x 12 blinded samples x 3 laboratories). The samples were "contrived stool samples" with H. pylori antigen spiked in. Data provenance is implied to be domestic (USA) due to the submission context, and it's a prospective study looking at controlled, contrived samples.
   • Preserved Specimen Storage Stability: Not explicitly stated how many samples were used, but the study was designed to validate stability claims.
   • Freeze/Thaw Stability: Not explicitly stated how many samples were used.
   • Analytical Specificity/Interference: Not explicitly stated how many samples were used, but testing was performed in the presence of various substances.
   • Analytical Specificity/Cross-reactivity: Not explicitly stated how many samples were used, but each organism was tested with a true negative and a contrived low positive sample at specified concentrations.
   • Method Comparison (Clinical Performance): 200 archived stool specimens were enrolled, of which 182 were evaluable and used for the comparison. Data provenance is of archived specimens from patients, suggesting retrospective data. The specific country of origin is not mentioned.

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

   • This device is an in-vitro diagnostic (IVD) for detecting antigens, not an imaging device requiring expert interpretation for ground truth.
   • For the Precision/Reproducibility study, "expected assay result" was used as ground truth for contrived samples. This implies the ground truth was based on the known concentration of spiked antigen.
   • For the Method Comparison study, the comparison was against an "FDA-cleared comparator device" and "Standard of Care (SoC) testing using an FDA-cleared commercial assay." The "ground truth" for clinical performance appears to be established by the results of these existing FDA-cleared methods. No human expert consensus was used to define the ground truth for individual samples.

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

   • No human adjudication method was mentioned or implied, as the device is an IVD detecting antigens, and ground truth was established either by known concentrations in contrived samples or by results from existing FDA-cleared assays.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No MRMC comparative effectiveness study was conducted. This type of study is typically performed for AI-assisted diagnostic imaging devices where human interpretation directly impacts results. This device is an immunoassay (IVD).

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

   • Yes, the performance data provided (LoD, Reproducibility, Interference, Cross-reactivity, Method Comparison) represent the standalone performance of the Premier HpSA Flex assay. It's an automated or semi-automated EIA, not an algorithm requiring human interaction for its direct output.

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

   • For analytical performance studies (LoD, Precision, Interference, Cross-Reactivity), the ground truth was known concentrations of H. pylori antigen in contrived samples or known presence/absence of interfering/cross-reacting substances/organisms.
   • For the method comparison (clinical performance), the ground truth was established by results from an FDA-cleared comparator device and Standard of Care (SoC) testing using an FDA-cleared commercial assay.

7. The sample size for the training set:

   • This is a traditional in-vitro diagnostic device (immunoassay), not a machine learning/AI algorithm that requires a "training set" in the conventional sense. The device's components and parameters are developed through standard chemistry and assay development processes, not through iterative training on a dataset.

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

   • As stated above, there is no "training set" for an immunoassay in the context of AI/ML. The "ground truth" for the development of the assay itself would align with standard analytical validation methods, ensuring the assay accurately detects the target analyte (H. pylori antigens) at various concentrations and in the presence of relevant interferents, against known standards.

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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 Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The provided document is an FDA 510(k) Substantial Equivalence Determination Decision Summary for the Revogene instrument.
Crucially, this submission (K222779) is a "Special 510(k)" for a firmware modification only, specifically to add a cooling sequence before lid opening in the event of a run interruption.

Therefore, the document does not contain information about a study to prove the device's diagnostic performance against acceptance criteria in the typical sense of analytical or clinical performance (e.g., sensitivity, specificity for detecting a disease). Instead, the performance demonstrated here relates to the safety feature implemented by the firmware update.

Based on the provided text, here's an analysis of the acceptance criteria and study that address the firmware modification:

1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly defines the acceptance criteria for this specific modification: the firmware update must successfully implement a cooling sequence before lid opening when a run is interrupted, to prevent access to hot parts.

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

The document does not detail specific sample sizes or data provenance (e.g., country of origin, retrospective/prospective) for testing this firmware modification. This is expected given the nature of a Special 510(k) for a safety-related firmware update. The FDA's decision to clear the device implies they were satisfied with the internal validation conducted by the manufacturer to demonstrate the successful implementation of this safety feature. No clinical data or large-scale analytical testing is typically required for such minor safety updates.

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

Not applicable for this type of firmware modification. The ground truth here is a functional safety requirement (i.e., "are hot parts accessible when a run is aborted after the update?"). This would be verified through engineering testing and safety assessments, not typically by expert consensus of clinical or radiological images.

4. Adjudication method for the test set:

Not applicable. This is not a study assessing diagnostic performance where adjudication of ambiguous results would be necessary.

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. This device is an instrument for molecular diagnostics (nucleic acid testing), not an AI-assisted diagnostic imaging device.

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

Not directly applicable in the typical sense (e.g., for an AI algorithm). The device itself operates "standalone" in its function of automated lysis, amplification, and detection, but the "performance" discussed here is a safety feature of its firmware, not its diagnostic accuracy.

7. The type of ground truth used:

The ground truth for this specific firmware modification is a functional safety performance objective. The "truth" is whether the cooling sequence activates as intended upon run interruption and whether it effectively prevents access to hot parts, thereby improving user safety. This would be established through engineering functional testing and safety verification protocols.

8. The sample size for the training set:

Not applicable. This is a firmware modification for a safety feature, not a machine learning algorithm that requires a "training set."

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

Not applicable. As above, no training set for a machine learning model is involved.

Summary of the document's relevance to your request:

The provided document is an FDA clearance letter for a firmware upgrade to an existing medical device, the Revogene instrument. This is a very specific type of submission (Special 510(k)) that focuses on demonstrating that a minor change does not adversely affect the device's safety or effectiveness, or alter its fundamental scientific technology.

Therefore, the typical metrics and study designs used for evaluating the diagnostic performance of new AI/ML-based devices (e.g., sensitivity, specificity, MRMC studies, ground truth established by expert consensus or pathology) are not present or applicable here. The "acceptance criteria" and "study" are focused solely on verifying the successful and safe implementation of the firmware's added cooling sequence upon run interruption.

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The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene was previously cleared under K170558. Meridian Biosciences, Inc. is submitting this 510(k) to implement a software modification to the Revogene that updates the current software with a PMT surveillance algorithm. The software monitors raw data fluorescence signal during assay testing and identifies issues due to a malfunction of the photomultiplier tube (the "PMT"), a key component in the Revogene instrument's optics system used in the management of fluorescence signals. Upon detection of a PMT malfunction, the PMT surveillance algorithm software produces a specific error code to the user labeled "Detection Error" and will lock the instrument thereby preventing further use.

The provided text describes a 510(k) submission for a software modification to the Revogene instrument, specifically the addition of a PMT (photomultiplier tube) surveillance algorithm. This modification is intended to monitor raw data fluorescence signals and identify issues due to a malfunction of the PMT, a key component in the instrument's optics system. Upon detection of a PMT malfunction, the algorithm produces an error code and locks the instrument, preventing further use.

The document states that this change does not affect the device's intended use nor alter the device's fundamental scientific technology. Therefore, the acceptance criteria and performance study details are focused on validating the new PMT surveillance algorithm's functionality and ensuring it does not negatively impact the previously cleared performance of the Revogene instrument.

Based on the provided text, a formal table of acceptance criteria and reported device performance, akin to what would be provided for a diagnostic or AI algorithm's clinical performance, is not explicitly present for the PMT surveillance algorithm itself. The document emphasizes that the modification is minor and focuses on the software's ability to detect and report PMT malfunctions.

However, we can infer the acceptance criteria and study proving the device meets them from the description of the software modification and the context of a 510(k) submission for a software update.

Here's a breakdown based on the provided information, addressing each point as much as possible:

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for this software modification is that the PMT surveillance algorithm successfully detects and reports PMT malfunctions. The reported performance would be the successful implementation of this functionality.

Inferred Acceptance Criteria Table:

Study Proving Acceptance Criteria:

The document implicitly indicates that a validation study was performed to demonstrate the functionality of the PMT surveillance algorithm. While details are scarce, the submission implies that the testing confirmed the algorithm's ability to detect PMT issues and trigger the appropriate error and lock-out mechanisms.

Detailed Study Information (Based on Inferences and General 510(k) Practices for Software Updates)

1. A table of acceptance criteria and the reported device performance:
   (See above table for inferred criteria and performance, as direct explicit table is not provided in the document for the new software feature). The document stresses that the overall performance characteristics of the Revogene instrument remain as previously cleared (K170558, K170557, etc.), and this software update doesn't change those.

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

   • Test Set Sample Size: Not explicitly stated for the PMT surveillance algorithm. For a software update of this nature (detecting a hardware malfunction), the "test set" would likely involve inducing PMT malfunctions (or simulating conditions that would lead to them) on multiple instruments to verify the algorithm's response. The general statement "The submitted information demonstrates that the modified Revogene instrument is safe, effective" implies a sufficient level of testing.
   • Data Provenance: Not specified. Given it's a software update for a commercialized instrument, the testing would typically be performed internally by the manufacturer (Meridian Bioscience, Inc.). It's likely retrospective in that it's testing a new feature on existing hardware, but the testing itself would be prospective for evaluating the new software. Country of origin not specified, but the manufacturer is based in Ohio, USA.

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

   • This is unlikely to involve a panel of "experts" in the same way an AI diagnostic algorithm's ground truth is established. The ground truth for a PMT malfunction would be a measurable hardware degradation or induced failure that clearly indicates the PMT is not functioning correctly. This would be established by engineers or instrument specialists, not clinical experts like radiologists.

4. Adjudication method for the test set:

   • Not applicable in the context of this software update. Adjudication methods like 2+1 or 3+1 are typically for establishing ground truth for subjective human interpretations (e.g., medical image reads). Here, the judgment is objective: either the PMT is malfunctioning or it's not, and the software either detects it or it doesn't.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done:

   • No. An MRMC study is not relevant for this type of software modification. MRMC studies are used to evaluate the impact of an AI algorithm on human reader performance for tasks involving perception and interpretation (e.g., diagnosing disease from medical images). This software is performing an automated internal diagnostic check on the instrument itself, not assisting human clinical interpretation.

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

   • Yes, implicitly. The PMT surveillance algorithm operates automatically as an internal check. Its performance is evaluated purely on its ability to detect PMT malfunctions and trigger the pre-defined error and lock-out, without human intervention in its real-time operation.

7. The type of ground truth used:

   • Instrumental/Hardware Ground Truth: The ground truth would be based on objective measurements and engineered conditions that reliably indicate a PMT malfunction within the Revogene instrument's optics system. This could involve simulating PMT degradation, intentionally causing component failures, or verifying against known hardware states.

8. The sample size for the training set:

   • Not specified. For a diagnostic algorithm like this, the "training set" would involve data collected from instrument operations, potentially including data from instruments with known good or failing PMT conditions, to develop and refine the detection algorithms. The complexity of the algorithm (e.g., rule-based vs. machine learning) would influence the need for and size of a specific "training set." Given the description, it sounds more like a rule-based or threshold-based detection system rather than a complex machine learning model that requires a large, annotated training set in the typical sense.

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

   • If a "training set" was used (e.g., for setting detection thresholds or developing rules), the ground truth would have been established by engineering teams through controlled experiments, measurements of PMT performance over time, and potentially by inducing known PMT issues on instruments. This would involve characterization of the instrument's optical signals under various conditions, including states indicative of PMT malfunction.

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Curian Campy, for use with the Curian Analyzer, is a rapid, qualitative fluorescent immunoassay for the detection of a Campylobacter-specific antigen in human fecal specimens. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in human stool from patients with signs and symptoms of gastroenteritis. The test is intended for use with unpreserved fecal specimens or preserved fecal specimens in transport media. Test results are to be used in conjunction with information available from the patient clinical evaluation and other diagnostic procedures. Curian Campy is intended to aid in the diagnosis of Campylobacter infection.

The Curian® Campy assay is a qualitative in vitro diagnostic test for the detection of Campylobacter-specific antigens in human stool samples collected from individuals with signs and symptoms of gastroenteritis. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in unpreserved or preserved stool in Cary-Blair or C&S transport media. The Curian® Campy assay utilizes fluorescence technology with the cleared Curian® Analyzer (K192817) to detect Campylobacter-specific antigens in human stool.

Here's a breakdown of the acceptance criteria and study details for the Curian Campy device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate section with predefined thresholds. However, based on the presentation of clinical performance data, the implicit acceptance criteria for sensitivity and specificity are demonstrated by the confidence intervals achieved in the clinical studies. For analytical performance, 100% agreement for certain categories and no observed interference/cross-reactivity are the implicit acceptance criteria.

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

• Prospective Clinical Study:
  • Sample Size: 1,474 specimens
  • Data Provenance: Prospective, collected from July 2020 to December 2020 at five clinical study sites across geographically distinct regions throughout the United States.
• Archived Clinical Study:
  • Sample Size: 290 archived samples
  • Data Provenance: Retrospective. The samples had prior culture and speciation results and were retrospectively tested.
• Contrived Study:
  • Sample Size: 210 specimens (150 positive, 60 negative).
  • Data Provenance: Contrived samples (spiked with Campylobacter species).
• Reproducibility Study:
  • Sample Size: 320 samples (160 unpreserved stool, 160 preserved stool in C&S media).
  • Data Provenance: Contrived samples, tested across three sites (one internal, two external).
• Prozone / Hook Effect Study:
  • Sample Size: 14 dilutions (n=7 for preserved, n=7 for unpreserved) tested in replicates of 5.
  • Data Provenance: Contrived samples.
• Cross-Reactivity/Microbial Interference Study:
  • Sample Size: Not explicitly stated as a number, but involves testing various bacteria, fungi, and viral strains (spiked into stool, some clinical Norovirus samples).
  • Data Provenance: Primarily contrived samples, with 5 clinical Norovirus stool specimens.
• Interfering Substances Study:
  • Sample Size: Not explicitly stated, but involves testing C. jejuni low positive contrived samples in the presence of 27 different chemical and biological substances.
  • Data Provenance: Contrived samples.
• Assay Reactivity/Inclusivity Study:
  • Sample Size: Not explicitly stated, but involves testing multiple strains of C. jejuni, C. coli, C. upsaliensis, and C. lari.
  • Data Provenance: Laboratory strains.
• Brush Bridging Study:
  • Sample Size: 53 non-pipettable clinical stool specimens (5 positive, 48 negative) from the prospective and archived clinical studies, plus a panel of contrived samples (25 at 3x LoD, 25 at 5x LoD, 25 negative).
  • Data Provenance: Clinical (from prior studies) and contrived.

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

• Ground Truth for Clinical Studies (Prospective and Archived): The ground truth was established by "standard of care Campylobacter culture and speciation" which is a laboratory method. There is no mention of human experts directly establishing the ground truth for classification of individual samples.
• Ground Truth for Contrived Studies (Reproducibility, Analytical Sensitivity, Prozone, Cross-Reactivity, Interfering Substances, Assay Reactivity): The ground truth was established by creating samples with known concentrations of organisms or by confirming the absence of organisms. This suggests laboratory verification rather than expert clinical assessment.

4. Adjudication Method for the Test Set

• Prospective Clinical Study: For specimens with discordant results between the Curian Campy assay and the reference method (culture and speciation), further evaluation was done using "FDA-cleared commercial nucleic acid amplification test (NAAT)". This acts as a form of adjudication for discordant results, though it's not a human consensus process.
• Archived Study, Contrived Studies, Analytical Performance Studies: No adjudication method is explicitly described for these studies other than the initial ground truth determination.

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 MRMC comparative effectiveness study was done.
• This device is an in-vitro diagnostic assay (Curian Campy) read by an automated analyzer (Curian Analyzer), not an AI assisting human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply.

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

• Yes, the performance data presented for the Curian Campy assay is standalone. The device (Curian Campy assay with the Curian Analyzer) provides a qualitative result (positive/negative) automatically. The interpretation of results is "automated by Curian Analyzer," and the clinical studies directly evaluate this automated output against a reference standard.

7. The Type of Ground Truth Used

• Clinical Studies (Prospective and Archived): The primary ground truth was culture and speciation for Campylobacter. For discordant results in the prospective study, an FDA-cleared commercial nucleic acid amplification test (NAAT) was used for further evaluation.
• Analytical Performance Studies (Reproducibility, Analytical Sensitivity, Prozone, Cross-Reactivity, Interfering Substances, Assay Reactivity, Contrived Study): The ground truth was based on known concentrations of spiked organisms or known negative samples, verified by laboratory methods.

8. The Sample Size for the Training Set

• The document does not describe algorithmic training. This device appears to be a fluorescence immunoassay interpreted by an analyzer, not a machine learning or AI algorithm that requires a separate training set. The descriptions of "analytical performance" and "clinical performance" are for evaluating the performance of the device itself, not for training an AI model.

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

• As there is no mention of an AI algorithm requiring a training set, this question is not applicable to the information provided.

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The Tosoh ST AIA-PACK BNP assay is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of BNP in human (K2EDTA) plasma on Tosoh AIA System Analyzers. BNP is used as an aid in the diagnosis of heart failure (HF) in patients presenting to the emergency department (ED) with clinical suspicion of new onset HF, acutely decompensated or exacerbated HF.

The ST AIA-PACK BNP is a two-site immunoenzymometric assay which is performed entirely in the ST AIA-PACK BNP test cups. BNP present in the test sample is bound with monoclonal antibody immobilized on magnetic beads and enzyme-labeled monoclonal antibody. The magnetic beads are washed to remove unbound enzyme-labeled monoclonal antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled monoclonal antibody that binds to the beads is directly proportional to the BNP concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using the curve.

The Tosoh ST AIA-PACK BNP Assay aims to extend its measuring interval beyond 2,000 pg/mL through manual and automated 1:5 and 1:10 dilutions. This is a special 510(k) submission, meaning it refers to a device that has already been cleared (K192380) and modifications were made to it that do not significantly alter its performance or safety (e.g., modified firmware, revised labeling, minor material changes, etc.). Since this is a Special 510(k) and not a de novo submission, this document is a justification for substantial equivalence to its predicate device (K192380), and does not contain detailed information for how the predicate device was evaluated.

Therefore, the study summary below only refers to the performance of the modified device compared to its predicate device, and not a full evaluation of the predicate device's performance.

1. Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and data provenance

The document does not specify the sample sizes used for the manual and automated dilution studies, nor does it specify the country of origin or whether the data was retrospective or prospective.

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

Not applicable. The ground truth method does not involve human experts; it relies on direct measurement.

4. Adjudication method for the test set

Not applicable. The ground truth method does not involve human experts.

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 versus without AI assistance

Not applicable. This is not an AI-assisted diagnostic device, but an in vitro diagnostic assay.

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

Not applicable. This device is an in vitro diagnostic assay, not an algorithm.

7. The type of ground truth used

The ground truth used for both manual and automated dilution studies is the recovery value of the BNP concentration after dilution, indicating the accuracy of the dilution process. This is a direct measurement based on the expected concentration after dilution.

8. The sample size for the training set

Not applicable. This device is an in vitro diagnostic assay and does not involve machine learning or a training set.

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

Not applicable. This device is an in vitro diagnostic assay and does not involve machine learning or a training set.

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The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liquid chromatography (HPLC). This test is an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.

The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High-Performance Liguid Chromatography (HPLC) system that separates and reports stable hemoglobin A1c (sA1c) percentage in venous whole blood. The operational portion of the G8 is composed of a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, smart media card, operation panel, and a printer. The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses ion-exchange HPLC for rapid, accurate, and precise separation of the stable form of HbA1c (sA1c) from other hemoglobin fractions. The G8 uses a non-porous cation exchange column and separates the hemoglobin components in the blood. Separation is achieved by utilizing differences in ionic interactions between the cation and exchange group on the column resin surface and the hemoglobin components in a step gradient elution. The hemoglobin fractions (designated as A1a. A1b. F. LA1c+, SA1c, A0, and, if present, H-V0, H-V2, H-V2 and H-V3) are subsequently removed from the column by performing a step-wise elution gradient using the varied salt concentrations in the Variant Elution Buffers HSi 1, 2 and 3. The peaks, H-V0, H-V1, H-V2 and H-V3 are typically presumptive HbAD, HbAS, HbAC and HbAE respectively. The software compares the retention times of hemoglobin fractions in a sample to the expected "windows of retention" and labels each fraction that correctly elutes within a defined expected window of retention. The software designates a hemoglobin fraction as POX (where X is the order of the peak as it elutes from the column) if it does not match a defined window of retention. All automated processes in the G8 are controlled by internal microprocessors, using software downloaded via a smart media card. The result report is printed and can be stored on the instrument. The data can be transmitted to a host computer through a bi-directional interface. The result report includes the sample ID, date, percentage and retention time of each fraction of hemoglobin, sA1c percentage and total A1 percentage, along with a chromatogram of the elution pattern of the hemoglobin fractions. If a sample contains a hemoglobin variant, the column elutes the fraction depending upon its charge.

The provided text describes the non-clinical performance testing of the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 (subject device) to support its substantial equivalence to a predicate device. This document focuses on the analytical performance of a diagnostic device rather than an AI/ML powered device, so some of the specific questions regarding AI/ML study design (e.g., number of experts, adjudication methods, MRMC studies) are not applicable.

Here's the information extracted from the document:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the statement "All performance testing results met their pre-determined acceptance criteria." While explicit numerical acceptance criteria for each test are not listed in a consolidated table, the discussion throughout the "Summary of Non-Clinical Performance Testing" implicitly defines them through the methodology and results. For example, for precision/repeatability, the claim of "imprecision at ≤ 2%" was a pre-established criterion. Similarly, for hemoglobin variant interference, "Non-clinically significant interference was defined as

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VR101 Lubricating Intravaginal Ring is a personal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity, and supplement the body's natural lubrication. This product is compatible with natural rubber latex and synthetic (polyurethane and polyisoprene) male condoms and FC2 female condoms.

The VR101 Lubricating Intravaginal Ring device is a lubricating intravaginal ring designed to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity, and supplement the body's natural lubrication. VR101 Lubricating Intravaginal Ring is constructed from a hollow biomedical grade hydrophilic polyether urethane (HPU) tube filled with a liquid vaginal lubricating solution comprised of a solution of glycerol (also known as glycerin), water, and sodium chloride. Upon insertion of VR101 Lubricating Intravaginal Ring in the vagina, the lubricating solution in the lumen ring is released through the semi-permeable wall of the tubing into the vagina, moisturizing and lubricating the vaginal mucosa without the use of any hormones or active pharmaceutical ingredients (APIs).

Each VR101 Lubricating Intravaginal Ring provides moisturization and lubrication for up to seven (7) days.

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

Device Name: VR101 Lubricating Intravaginal Ring

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally established by the "Specification" column, and the reported performance is in the "Results" column. Many of the reported results indicate "Pass" or adherence to the specification.

2. Sample Size for the Test Set and Data Provenance

Non-Clinical (Performance/Biocompatibility) Test Set:

• The exact sample sizes for each non-clinical test are not explicitly detailed in the summary. However, tests were conducted on "all t=0 samples and samples exposed to accelerated aging conditions equivalent to 54 months storage" and "all as-prepared lubricating and packaging solution samples". This implies multiple samples were used for each test condition.
• Data Provenance: Not specified, but generally these are conducted in laboratory settings (in-vitro or animal studies, as indicated by ISO standards).

Clinical Test Set (CI03 study, which demonstrated efficacy for the primary endpoint):

• Sample Size: 175 participants (87 in treatment group, 88 in sham group). 166 (94.9%) completed the study.
• Data Provenance: United States (two-site clinical investigation), prospective (randomized, sham-controlled trial).

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

• Non-Clinical Tests: Ground truth is established by the test methodologies themselves (e.g., ISO standards, USP standards, ASTM standards) and objective measurements. No human experts establishing a subjective "ground truth" are mentioned for these tests.
• Clinical Tests (CI03): The primary efficacy endpoint for CI03 was assessed using the Female Sexual Function Index (FSFI) - Lubrication domain (FSFI-LD). This is a patient-reported outcome measure, meaning the "ground truth" reflecting the efficacy is based on the participants' subjective experience and reporting, not on expert consensus. The study was double-blind, aiming to minimize bias in both participants' and researchers' assessments.

4. Adjudication Method for the Test Set

• Non-Clinical Tests: No adjudication method described; results are objective measurements against defined specifications.
• Clinical Tests (CI03): No external adjudication method is mentioned for the clinical trial results. Data collection for FSFI is typically self-reported by participants. The study was double-blind, implying that neither the participants nor the investigators knew which treatment (VR101 or sham) each participant received, which serves as a method to mitigate bias in outcome assessment.

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 MRMC study was done. This device is a medical device (intravaginal ring) for lubrication, not an AI-powered diagnostic or imaging device that would typically involve human readers or AI assistance. Therefore, this question is not applicable.

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

• Not applicable. The VR101 is a physical medical device, not an algorithm, so the concept of standalone algorithm performance does not apply.

7. The Type of Ground Truth Used

• Non-Clinical Tests: Objective measurements against established scientific/regulatory standards (ISO, USP, ASTM) and device specifications.
• Clinical Tests (CI03): Patient-reported outcomes (Female Sexual Function Index - Lubrication domain) for efficacy, and adverse event reporting for safety.

8. The Sample Size for the Training Set

• Not applicable. This device is not an AI/ML algorithm that requires a "training set." The clinical studies (CI01, CI02, CI03) served as research and development and pivotal studies to demonstrate safety and efficacy.

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

• Not applicable. As stated above, there is no "training set" for this type of device.

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Curian HpSA, for use with the Curian Analyzer, is a rapid, qualitative, fluorescent immunoassay for the detection of Helicobacter pylori antigen in human stool. Test results are intended to aid in the diagnosis of H, pylori infection and to demonstrate loss of H. pyloriantigen following treatment. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least following completion of therapy. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.

The Curian™ HpSA® assay is a qualitative in vitro diagnostic test for the detection of Helicobacter pylori in human stool. The Curian™ HpSA® assay utilizes fluorescence technology with the newly developed Curian™ Analyzer to detect H. pylori antigen. The Curian™ Analyzer has been designed to disposition sample results from lateral flow immunoassays.

Here's a breakdown of the acceptance criteria and study information for the Curian™ HpSA® and Curian™ Analyzer, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance study aiming for substantial equivalence to an FDA-cleared predicate device. The predicate device had a demonstrated sensitivity and specificity ≥ 95%, with a lower bound of the two-sided 95% confidence interval (CI) greater than 89% against a composite reference method. Therefore, the new device's agreement with this predicate is the key performance metric assessed.

2. Sample Sizes and Data Provenance

• Test Set Sample Size: 542 evaluable specimens.
• Data Provenance: The specimens were from the intended use population, collected in a multi-center method comparison study conducted at three sites in the USA. The study appears to be prospective in nature, as it "evaluated" the device for detecting H. pylori stool antigen in human stool.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

This information is not explicitly provided in the document for the test set. The clinical study compares the new device to an "FDA-cleared H. pylori stool antigen EIA" which was itself previously evaluated against a composite reference method. The document does not describe the establishment of the ground truth for this specific study's test set, nor the number or qualifications of experts involved in that.

4. Adjudication Method (Test Set)

The primary comparison is between the new device and an FDA-cleared comparator EIA. However, in cases of discordance, PCR was used for adjudication:

• "2/3 Curian HpSA false negatives were dispositioned as negative by PCR"
• "8/14 Curian HpSA false positives were dispositioned as positive by PCR"

This suggests a form of supplementary adjudication using a molecular method for discordant results between the new device and the comparator EIA.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This document describes the performance of a diagnostic assay (Curian™ HpSA®) in a standalone clinical comparison against another assay, not the improvement of human readers with AI assistance.

6. Standalone Performance

Yes, a standalone performance study was done. The document explicitly describes the "Comparison of Curian™ HpSA® assay to an FDA-cleared H. pylori Stool Antigen EIA" focusing on the device's accuracy in detecting H. pylori antigen in human stool samples. The device itself (the Curian™ Analyzer) interprets the results from the lateral flow immunoassay.

7. Type of Ground Truth Used (Test Set)

The "ground truth" for the current study is effectively the results from an FDA-cleared H. pylori stool antigen EIA. This predicate EIA was, in turn, previously established against a "composite reference method (i.e., culture, histology, and RUT) for initial H. pylori diagnosis." So, indirectly, the ultimate ground truth is a composite reference method.

8. Sample Size for Training Set

The document does not provide information on the sample size used for the training set. This is an in vitro diagnostic device, and details about its internal algorithm training (if any is applicable beyond general assay development) are not disclosed in this 510(k) summary.

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

The document does not provide information on how the ground truth for the training set was established, as details about training sets are not included in this summary.

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