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I am sorry, but the provided text from the FDA 510(k) clearance letter for the xTAG Gastrointestinal Pathogen Panel (GPP) does not contain the specific information required to answer your questions about acceptance criteria and the detailed study that proves the device meets those criteria.

The letter primarily confirms the substantial equivalence of the device to a predicate device and outlines regulatory requirements. It does not include:

• A table of acceptance criteria and reported device performance.
• Details about the sample size used for a test set, data provenance, or the number/qualifications of experts.
• Information on adjudication methods, MRMC studies, standalone performance, or the type of ground truth used.
• Details regarding the training set's sample size or ground truth establishment.

To obtain this information, you would typically need to refer to the 510(k) summary document or the full 510(k) submission (if publicly available), which often contain the study design and results for substantial equivalence demonstrations. The letter itself is a notice of clearance, not a comprehensive study report.

Ask a specific question about this device

The xTAG Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral, bacterial and parasitic nucleic acids in human stool specimens or human stool in Cary-Blair media from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes, and toxin genes are identified using the xTAG GPP: Viruses •Adenovirus 40/41 •Norovirus GI/GII •Rotavirus A Bacteria ·Campylobacter (C. jejuni, C. coli, and C. lari only) ·Clostridium difficile (C. difficile) toxin A/B •Escherichia coli (E. coli) O157 · Enterotoxigenic E. coli (ETEC) LT/ST •Salmonella •Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2 ·Shigella (S. boydii, S. sonnei, S. flexneri, and S. dysenteriae) · Vibrio cholerae (V. cholerae) cholera toxin gene (ctx) Parasites •Cryptosporidium (C. parvum and C. hominis only) ·Entamoeba histolytica (E. histolytica) · Giardia (G. lamblia only, also known as G. intestinalis and G. duodenalis) The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestion when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks. xTAG GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAG GPP results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease. xTAG GPP is not intended to monitor or guide treatment for C. difficile infections. The xTAG GPP test is indicated for use with the Luminex 100/200™ and MAGPIX instruments with xPONENT software.

The xTAG Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral, bacterial and parasitic nucleic acids in human stool specimens or human stool in Cary-Blair media from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes, and toxin genes are identified using the xTAG GPP: Viruses •Adenovirus 40/41 •Norovirus GI/GII •Rotavirus A Bacteria ·Campylobacter (C. jejuni, C. coli, and C. lari only) ·Clostridium difficile (C. difficile) toxin A/B •Escherichia coli (E. coli) O157 · Enterotoxigenic E. coli (ETEC) LT/ST •Salmonella •Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2 ·Shigella (S. boydii, S. sonnei, S. flexneri, and S. dysenteriae) · Vibrio cholerae (V. cholerae) cholera toxin gene (ctx) Parasites •Cryptosporidium (C. parvum and C. hominis only) ·Entamoeba histolytica (E. histolytica) · Giardia (G. lamblia only, also known as G. intestinalis and G. duodenalis) The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestion when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks. xTAG GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAG GPP results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease. xTAG GPP is not intended to monitor or guide treatment for C. difficile infections. The xTAG GPP test is indicated for use with the Luminex 100/200™ and MAGPIX instruments with xPONENT software.

The provided document does not contain information about the acceptance criteria or a study proving that the device meets those criteria. The document is an FDA 510(k) clearance letter for the xTAG Gastrointestinal Pathogen Panel (GPP), outlining its indications for use and regulatory information. It does not detail the specific performance study results, acceptance criteria, or the methodology of such a study.

Therefore, I cannot provide the requested information based on the given input.

Ask a specific question about this device

The xTAG® Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral, bacterial and parasitic nucleic acids in human stool specimens or human stool in Cary-Blair media from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes and toxin genes are identified using the xTAG GPP:

Viruses

• · Adenovirus 40/41
• · Norovirus GI/GII
• · Rotavirus A

Bacteria

• · Campylobacter (C. jejuni, C. coli and C. lari only)
• · Clostridium difficile (C. difficile) toxin A/B
• · Escherichia coli (E. coli) O157
• · Enterotoxigenic E. coli (ETEC) LT/ST
• · Salmonella
• · Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2
• · Shigella (S. boydii, S. sonnei, S. flexneri and S. dysenteriae)
• · Vibrio cholerae (V. cholerae) cholera toxin gene (ctx)

Parasites

• · Cryptosporidium (C. parvum and C. hominis only)
• · Entamoeba histolytica (E. histolytica)
• · Giardia (G. lamblia only, also known as G. intestinalis and G. duodenalis)

The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestion when used in conjunction with clinical evaluation, laboratory findings and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks.

xTAG GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAG GPP results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

xTAG GPP is not intended to monitor or guide treatment for C. difficile infections.

The xTAG GPP test is indicated for use with the Luminex® 100/200™ and MAGPIX® instruments with xPONENT® software.

Not Found

The provided text is a 510(k) clearance letter for the xTAG Gastrointestinal Pathogen Panel (GPP) and xTAG Data Analysis Software (TDAS GPP). While it details the "Indications for Use" and general regulatory information, it does not contain the specific technical acceptance criteria, study details, or performance data for the device.

Therefore, I cannot provide the requested information based on the given input.

To answer your request, I would need a section of the document that describes the clinical performance study, often found in a "Performance Data" or "Clinical Study Results" section of a 510(k) submission. This section typically includes:

• Acceptance Criteria: Predetermined performance targets (e.g., sensitivity, specificity, positive predictive agreement, negative predictive agreement thresholds).
• Reported Device Performance: The actual sensitivity, specificity, and other metrics achieved by the device in the study.
• Study Design: Details about the sample size, data provenance, ground truth establishment, and any comparison to predicate devices or reference methods.

Without this information in the provided text, I am unable to populate the table or answer the specific questions about the study design.

Ask a specific question about this device

The xTAG® Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral, bacterial and parasitic nucleic acids in human stool specimens or human stool in Cary-Blair media from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes and toxin genes are identified using the xTAG GPP:

Viruses

• · Adenovirus 40/41
• · Norovirus GI/GII
• · Rotavirus A

Bacteria

• · Campylobacter (C. jejuni, C. coli and C. lari only)
• · Clostridium difficile (C. difficile) toxin A/B
• · Escherichia coli (E. coli) O157
• · Enterotoxigenic E. coli (ETEC) LT/ST
• · Salmonella
• · Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2
• · Shigella (S. boydii, S. sonnei, S. flexneri and S. dysenteriae)
• · Vibrio cholerae (V. cholerae) cholera toxin gene (ctx)

Parasites

• · Cryptosporidium (C. parvum and C. hominis only)
• · Entamoeba histolytica (E. histolytica)
• · Giardia (G. lamblia only, also known as G. intestinalis and G. duodenalis)

The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestion when used in conjunction with clinical evaluation, laboratory findings and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks.

xTAG GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAG GPP results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

xTAG GPP is not intended to monitor or guide treatment for C. difficile infections.

The xTAG GPP test is indicated for use with the Luminex® 100/200™ and MAGPIX® instruments with xPONENT® software.

Not Found

The provided text is a 510(k) premarket notification for the xTAG Gastrointestinal Pathogen Panel (GPP) and xTAG Data Analysis Software (TDAS GPP). It outlines the device's intended use and the FDA's decision regarding its substantial equivalence. However, it does not contain information about specific acceptance criteria, study details, sample sizes, expert qualifications, or ground truth establishment for the performance of the device itself.

The document mainly focuses on:

• Regulatory information: Device name, regulation number, regulatory class, product code, and the FDA's decision of substantial equivalence.
• Indications for Use: A detailed description of the pathogens the xTAG GPP can detect, from what sample type, and for what purpose (diagnosis of gastrointestinal infection, aid in outbreak detection). It also includes important disclaimers about the presumptive nature of positive results, the need for confirmation, and limitations of the test.
• Intended Use Environment: Specifies the instruments the test is indicated for use with.

Therefore, I cannot provide the requested information from the given text. To answer your questions, I would need a different type of document, such as a summary of safety and effectiveness data (SSED), a clinical study report, or the full 510(k) submission which would detail the validation studies.

Ask a specific question about this device

The xTAG® Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral, bacterial, and parasitic nucleic acids in human stool specimens or human stool in Cary-Blair media from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes and toxin genes are identified using the xTAG GPP:

Viruses

• . Adenovirus 40/41
• Norovirus GI/GII ●
• Rotavirus A

Bacteria

• Campylobacter (C. jejuni, C. coli and C. lari only) .
• Clostridium difficile (C. difficile) toxin A/B ●
• Escherichia coli (E. coli) 0157
• Enterotoxigenic Escherichia coli (ETEC) LT/ST
• . Salmonella
• Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2 ●
• Shigella (S. boydii, S. sonnei, S. flexneri and S. dysenteriae)
• Vibrio cholerae (V. cholerae) cholera toxin gene (ctx)

Parasites

• Cryptosporidium (C. parvum and C. hominis only) .
• Entamoeba histolytica (E. histolytica) ●
• . Giardia (G. lamblia only - also known as G. intestinalis and G. duodenalis)

The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation, laboratory findings and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.

xTAG GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAG Gastrointestinal Pathogen Panel results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

xTAG GPP is not intended to monitor or guide treatment for C. difficile infections.

The xTAG GPP is indicated for use with the Luminex® 100/200™ instrument system with xPONENT® software.

xTAG GPP incorporates a multiplex reverse-transcription polymerase chain reaction (RT-PCR) with Luminex's proprietary universal sorting system (the xTAG Universal Array) on the Luminex platform. The xTAG Universal Array sorts nucleic acids onto discreet Luminex bead populations by virtue of highly specific "tag/anti-tag" hybridization reactions. The tags and anti-tags comprising the xTAG Universal Array are 24-mer oligonucleotide sequences not found in nature. The assay has been designed to simultaneously detect microbial targets and an internal control (bacteriophage MS2 added to each sample prior to extraction).

For each sample, 10 µL of extracted nucleic acid is amplified in a single multiplex RT-PCR reaction. Amplimers ranging from 58 to 202 bp (not including the 24-mer tag) are generated in this reaction. A five μL aliquot of the RT-PCR product is then subjected to a hybridization/detection reaction that also includes bead populations coupled to 24-mer antitags. Each bead population is coupled to a unique anti-tag which is the exact complement of a 24-mer tag incorporated into a given amplimer. Thus, each Luminex bead population uniquely identifies a microbial target or assay control through a specific tag/anti-tag hybridization reaction. Signal is generated via a Streptavidin, R-Phycoerythrin conjugate.

The Luminex instrument sorts the products of these hybridization reactions and generates a signal in the form of a median fluorescence intensity (MFI) value for each bead population. The MFI values are generated by the xPONENT software provided with the instrument using the GPP protocol parameters, and are analyzed by the xTAG Data Analysis Software (TDAS GPP (US)). TDAS GPP (US) applies algorithms to MFI values in order to generate a qualitative result for each microbial target selected for reporting to establish the presence or absence of bacterial, viral or parasitic targets and/or controls in each sample. The data analysis software also generates a qualitative result and compiles a report for patient samples and external controls assayed in a given run. Before data are analyzed, a user has the option to select a subset of the targets from the intended use of the xTAG GPP (for each sample).

Here's a summary of the acceptance criteria and study information for the xTAG Gastrointestinal Pathogen Panel (GPP) device, based on the provided text:

Acceptance Criteria and Device Performance

The acceptance criteria are generally established as ranges or thresholds for performance metrics. For specific analytes, detailed ranges for Mean MFI and %CV are provided as device performance, particularly in the reproducibility studies for Low Positive (LP) and Moderate Positive (MP) samples. Overall, the qualitative agreement with expected results and confidence intervals (95% CI) are the primary indicators of acceptance for both analytical and clinical performance.

Note on Table Content: Due to the extensive nature of the data, a comprehensive single table with all acceptance criteria and reported performance for every analyte across all studies would be extremely large. The table below focuses on general acceptance criteria mentioned for clinical performance and provides examples of reported performance for the additional analytes emphasized in this submission (Adenovirus 40/41, Entamoeba histolytica, Vibrio cholerae). For full details on all analytes from the original submission (K121454), one would need to consult that document.

Study Details

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

   • Analytical Reactivity: Empirical testing of a wide range of clinically relevant GI pathogen strains, genotypes, and isolates. For new analytes, specific strains (e.g., Adenovirus 40/41 from Zeptometrix, CDC; E. histolytica from ATCC; V. cholerae from NCTC, ATCC) were used. Additionally, sequencing analysis was performed on 9 Adenovirus 40 and 28 Adenovirus 41 clinical samples.
   • Carry-over Contamination: 144 High Negative samples and 144 High Positive samples for Adenovirus 40, run in a checkerboard manner in duplicate after 6 independent extractions.
   • Limit of Detection (LoD): Serial dilutions of simulated samples in negative clinical stool matrix, confirmed with at least 20 replicates of the selected dilution for each analyte.
   • Repeatability: 20 replicates for each of two different analyte concentrations (LoD and 5x-10x above cut-off MFI).
   • Analytical Specificity: Organisms (cross-reactivity, interference) tested at high positive titers, panel analytes at low positive concentrations. Specific numbers of organisms are not consistently provided for all tests but mentioned for E. dispar strains (ATCC PRA-353, PRA-368).
   • Fresh vs. Frozen Stability: Sets of simulated specimens prepared at Low Positive, Moderate Positive, and High Positive concentrations. Specific numbers are not explicitly stated for each level but indicate replicates were run.
   • Precision/Reproducibility: 90 replicates for each single analyte and dual analyte sample (3 replicates per run x 5 runs per operators per site x 3 sites).
   • Stool in Cary-Blair Media LoD Study: Serial dilutions for Clostridium difficile, Giardia lamblia, Norovirus GII (representative analytes). 20 replicates for each LoD titer.
   • Asymptomatic Volunteers (Clinical Study): 200 clinical stool samples. Data was analyzed for 192 samples due to PCR inhibition.
   • Prospective Clinical Study (Stool): 1407 clinical specimens. Collected prospectively between June 2011 and February 2012 from pediatric and adult patients. Data provenance: 4 laboratories in the United States (Arizona, Missouri, Tennessee, Texas) and 2 in Southern Ontario (Canada).
   • Prospective Clinical Study (Stool in Cary-Blair): A subset of samples from the 1407 prospective study for which adequate sample was available.
   • Pre-selected Stool Specimens (Retrospective Study): 207 archived stool specimens. Collected retrospectively from multiple sites in North America, Africa, and Europe.
   • Pre-selected Stool in Cary-Blair Specimens (Retrospective Study): Remnants of available pre-selected frozen stool specimens mixed proportionally with Cary-Blair.
   • Supplemental Clinical Data (Simulated Stool/Cary-Blair): 50 negative, 50 positive E. histolytica, 50 positive V. cholerae simulated stool specimens. 50 negative, 50 positive Adenovirus 40/41, 50 positive E. histolytica, 50 positive V. cholerae simulated stool in Cary-Blair specimens.
   • Botswana Pediatric Stool Specimens (Retrospective Study): 313 pediatric stool specimens. Collected prospectively between February 2011 and January 2012 from symptomatic pediatric patients in Botswana, Africa.

2. 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):

   The document does not explicitly state the number or specific qualifications (e.g., years of experience) of experts involved in establishing ground truth. However, it indicates:

   • Reference/Comparator methods: For the clinical studies, reference/comparator methods were used at central laboratories independent of xTAG GPP testing sites. These methods included Premier Adenoclone Type 40/41 EIA, Amplification + sequencing (one NAAT+), Microscopy, and Bacterial culture.
   • Sequencing analysis: Bi-directional sequencing with analytically validated primers was performed. This implies expertise in molecular biology and sequence analysis.
   • Clinical evaluation: The study was conducted at 6 independent laboratories (4 in US, 2 in Canada) for the prospective study, and 4 sites for the retrospective study (3 external to Luminex Molecular Diagnostics - LMD). This suggests that the ground truth assessment, particularly for clinical diagnosis and interpretation of comparator methods, involved multiple trained laboratory personnel and clinicians.

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

   The document describes confirmatory testing for discrepant results, particularly in the retrospective and Botswana studies. This often implies an adjudication process:

   • For positive xTAG GPP results not pre-selected at the banking site, confirmatory testing by nucleic acid amplification followed by bi-directional sequencing was performed to determine if these were True Positive or False Positive.
   • For certain analytes in the Botswana study, a random subset of xTAG GPP negative samples was also assessed by nucleic acid amplification and bi-directional sequencing.
   • One specimen that was positive for Adenovirus 40/41 by comparator but negative by xTAG GPP was positive by bi-directional sequencing only (i.e. FDA-cleared EIA negative).
   • These actions suggest a form of discrepant analysis, where a more definitive "gold standard" (like sequencing) is used to adjudicate differences. However, a formal "m+n" type adjudication (e.g., 2+1, 3+1) involving a panel of experts for every case is not explicitly stated. The comparator methods themselves serve as the primary reference standard, with sequencing as a confirmatory tool for discrepancies.

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 device is a diagnostic assay (in vitro diagnostic device), not an AI-assisted imaging or diagnostic tool that involves human readers interpreting results with or without AI assistance. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human reader improvement with AI vs. without AI assistance was not performed. The evaluation is focused on the standalone performance of the assay itself compared to existing reference methods.

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

   Yes, a standalone performance evaluation was done. The entire analytical and clinical performance studies described (analytical reactivity, LoD, repeatability, specificity, stability, reproducibility, clinical prospective, retrospective, and supplemental studies) are all assessments of the algorithm-only performance of the xTAG GPP device. The device automates the detection and identification of nucleic acids from pathogens, and the results are qualitatively interpreted by the xTAG Data Analysis Software (TDAS GPP (US)) which applies algorithms to MFI values to generate a "positive" or "negative" result. Human involvement is in sample preparation, running the instrument, and reviewing the generated report, but the "performance" discussed is that of the assay and its associated software for detection, not human interpretation aided by AI.

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

   The ground truth was primarily established through reference/comparator methods, which varied by pathogen:

   • Composite Comparator: For Adenovirus 40/41 (Premier Adenoclone Type 40/41 EIA + Amplification + sequencing).
   • Bacterial Culture: For Vibrio cholerae.
   • Microscopy followed by Amplification + Sequencing: For Entamoeba histolytica (positive specimens by microscopy only).
   • Nucleic Acid Amplification Tests (NAATs) followed by bi-directional sequencing: Used for confirmatory testing of discrepant results across various analytes.
   • In-house real-time PCR: Used for some confirmations (e.g., Giardia, Adenovirus).
     These methods represent established diagnostic assays and molecular techniques, often considered "gold standards" or highly accurate reference methods in clinical microbiology.

7. The sample size for the training set:

   The document describes various analytical and clinical studies, but it does not explicitly mention a "training set" in the context of machine learning model development. This is typical for traditional in vitro diagnostic devices. The performance evaluation focuses on validation, not iterative training and testing of an AI model.

   However, if we broadly interpret "training set" as data used during the development and initial optimization before formal validation:

   • The document states that the reagents were unchanged from a previous submission (K121454). This implies development and some level of internal testing and optimization (akin to a training phase) would have occurred prior to that submission using various pathogen strains and clinical samples to establish the assay's parameters.
   • The "Analytical Reactivity" studies involve testing a wide range of strains to establish reactivity, which could be considered part of an iterative development process that feeds into refinement.

   Without specific details on Luminex's internal development process, a distinct "training set" with a defined sample size for an AI algorithm is not identified in this regulatory submission.

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

   Since a discrete "training set" for an AI algorithm is not explicitly identified, the method for establishing ground truth for such a set is also not detailed.
   However, for the general development and optimization of the assay:

   • Known strains and characterized clinical specimens: Analytical studies like analytical reactivity and LoD determination use well-characterized, often commercially available, strains (e.g., ATCC, Zeptometrix, NCTC) and high-titer clinical specimens where the presence and concentration of the pathogen are already known through established microbiological and molecular techniques. These serve as the "ground truth" for calibrating and optimizing assay parameters (like MFI cut-offs) during development.
   • Reference methods: Any prior development would have relied on the same types of reference methods (culture, EIA, PCR/sequencing) that were used to establish ground truth in the formal validation studies.

Ask a specific question about this device

The xTAG® Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple viral. parasitic, and bacterial nucleic acids in human stool specimens from individuals with signs and symptoms of infectious colitis or gastroenteritis. The following pathogen types, subtypes and toxin genes are identified using the xTAG® GPP:

• · Campylobacter (C. jejuni, C. coli and C. lari only)
• · Clostridium difficile (C. difficile) toxin A/B
• · Cryptosporidium (C. parvum and C. hominis only)
• Escherichia coli (E. coli) O157
• Enterotoxigenic Escherichia coli (ETEC) LT/ST
• · Giardia (G. lamblia only also known as G. intestinalis and G. duodenalis)
• · Norovirus GI/GII
• Rotavirus A
• · Salmonella
• · Shiga-like Toxin producing E. coli (STEC) stx 1/stx 2
• · Shigella (S. boydii, S. sonnei, S. flexneri and S. dysenteriae)

The detection and identification of specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation, laboratory findings and epidemiological information. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.

xTAG® GPP positive results are presumptive and must be confirmed by FDA-cleared tests or other acceptable reference methods.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out coinfection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative xTAGGastrointestinal Pathogen Panel results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

xTAG® GPP is not intended to monitor or guide treatment for C. difficile infections.

The xTAG® GPP is indicated for use with the Luminex® 100/200™ instrument.

The Luminex Molecular Diagnostics xTAG GPP consists of kit reagents and software. The reagents in conjunction with a thermal cycler are used to perform nucleic acid amplification (reverse transcription-polymerase chain reaction, or RT-PCR/PCR), and the protocol configuration file is used to generate results while the data analysis software (TDAS GPP (US)) is used to analyze the results from the Luminex Corporation Luminex 100/200 instrument system (which includes the xPONENT core software).

The components of the xTAG GPP kit are contained within 2 boxes (one that is frozen, and one that is refrigerated). The kit is shipped with the xTAG GPP CD which contains the xTAG GPP T-A (LX) protocol configuration file and the TDAS GPP (US) software. The instrument is shipped with the xPONENT software.

The xTAG Gastrointestinal Pathogen Panel (xTAG GPP) incorporates multiplex reverse transcription and polymerase chain reaction (RT-PCR / PCR) with Luminex's proprietary universal tag sorting system on the Luminex platform. The assay also detects an internal control (bacteriophage MS2) that is added to each sample prior to extraction. Each sample is pre-treated prior to extraction and is then put through extraction using the Biomerieux NucliSens EasyMag kit (product code JJH, class I, an IVD-labeled automated system for nucleic acid extraction).

Post-extraction, for each sample, 10 uL of extracted nucleic acid is amplified in a single multiplex RT-PCR/PCR reaction. Each target or internal control in the sample results in PCR amplicons ranging from 58 to 202 bp (not including the 24-mer tag). A five uL aliquot of the RT-PCR product is then added to a hybridization/detection containing bead populations coupled to sequences from the Universal Array ("antitags"), streptavidin, R-phycoerythrin conjugate. Each Luminex bead population detects a specific microbial target or control through a specific tag/anti-tag hybridization reaction. Following the incubation of the RT-PCR products with the xTAG GPP Bead Mix and xTAG Reporter Buffer, the Luminex instrument sorts and reads the hybridization/detection reactions.

A signal, or median fluorescence intensity (MFI), is generated for each bead population. These fluorescence values are analyzed to establish the presence of bacterial, viral or parasitic targets and/or controls in each sample. A single multiplex reaction identifies all targets.

The xTAG Data Analysis Software for the Gastrointestinal Pathogen Panel (TDAS GPP (US)) analyzes the data to provide a report summarizing which pathogens are present. Before data are analyzed, a user has the option to select a subset of the targets from the intended use of the xTAG GPP (for each sample). Consequently the remaining target results are masked and cannot be retrieved.

Target results above or equal to the cutoff are considered positive, while target results below the cutoff are considered negative. For each sample analyzed by TDAS GPP (US), there are individual results for each of the targets and the internal control (bacteriophage MS2).

Acceptance Criteria & Study Results for xTAG® Gastrointestinal Pathogen Panel (GPP)

This document describes the acceptance criteria and study results for the xTAG® Gastrointestinal Pathogen Panel (GPP), a qualitative nucleic acid multiplex test for the simultaneous detection and identification of multiple viral, parasitic, and bacterial nucleic acids in human stool specimens.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for clinical performance are implicitly defined by the reported sensitivity and specificity (or Positive Percent Agreement and Negative Percent Agreement) for each analyte, with a 95% Confidence Interval (CI) lower bound typically being the minimum acceptable performance. The provided study data shows the performance relative to reference/comparator methods.

Note on Acceptance Criteria: Explicit quantitative acceptance criteria (e.g., "Sensitivity must be >X%") are not explicitly stated in the provided text as an overarching target. However, the FDA's acceptance of the de novo classification implies that the presented clinical performance data, including these sensitivity/specificity/agreement ranges with their 95% CIs, were deemed sufficient for the intended use and risk-benefit profile. The FDA's review and ultimate acceptance of the de novo classification indicate that the device "meets the acceptance criteria" as evaluated against relevant standards and guidance documents. The FDA also notes concerns regarding "relatively low specificity of two of the analytes tested in the panel (C. difficile and Norovirus)," but considers these addressed by labeling requirements for confirmation.

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

Prospective Clinical Study:

• Sample Size: 1407 clinical stool specimens (from 1407 subjects) were included in the primary prospective study after exclusions. An additional 200 asymptomatic donor samples were tested for baseline levels.
• Data Provenance: Prospective, collected from six clinical laboratories in North America (four sites in the U.S. and two sites in Canada) between June 2011 and February 2012.

Retrospective Clinical Study 1 (Pre-Selected Specimens):

• Sample Size: 203 pre-selected positive clinical specimens and 277 "negative" clinical specimens (total 480) were tested.
• Data Provenance: Retrospective, collected at multiple sites in North America and Europe.

Supplemental Clinical Study (Botswana Pediatric Stool Specimens):

• Sample Size: 313 pediatric stool specimens.
• Data Provenance: Prospective, collected between February 2011 and January 2012 from symptomatic pediatric patients admitted to two referral hospitals in Botswana, Africa.

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" used to establish ground truth for the test sets in a single, overarching assessment. Instead, the ground truth was established through a combination of:

• Routine diagnostic algorithms used at the clinical sites (e.g., bacterial culture, EIA/DFA, microscopic examination, real-time PCR, nucleic acid amplification tests followed by bi-directional sequencing). The qualifications of personnel performing these routine diagnostics are implied to be standard for clinical laboratory settings but not specified in detail (e.g., "trained clinical laboratory personnel").
• Reference and comparator method testing conducted at central laboratories, independent of xTAG GPP testing sites. These methods included various FDA-cleared assays and analytically validated PCR/sequencing assays. The scientific rigor of these methods implies expert oversight in their performance and interpretation, but specific expert qualifications (e.g., "radiologist with 10 years of experience") are not provided for the individuals performing these reference tests or adjudicating results.

For the composite comparator methods (e.g., Norovirus, ETEC, Rotavirus), the interpretation algorithms and sequencing criteria suggest a structured, expert-defined process, but the number and specific qualifications of individuals involved in defining these are not enumerated.

4. Adjudication Method for the Test Set

The adjudication method employed was primarily discrepant analysis using analytically validated PCR/sequencing assays or FDA-cleared molecular assays.

• In the Prospective Clinical Study, discrepant results between the xTAG GPP and the initial reference methods were evaluated using these advanced molecular methods. The final performance metrics (Sensitivity, Specificity, PPA, NPA) were calculated "After Discrepant Investigation," indicating that the results of the discrepant analysis were incorporated to refine the "true" status of the samples.
• Similarly, in the Retrospective and Supplemental Studies, xTAG GPP positive results for analytes not initially targeted by the comparator were subjected to PCR/bi-directional sequencing for confirmation.

There is no mention of a specific "X+Y" type of adjudication involving multiple human readers beyond the standard clinical laboratory and molecular testing procedures.

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 done. The study's focus was on the performance of the xTAG GPP device against established laboratory reference methods, not on comparing human reader performance with and without AI assistance. The xTAG GPP is an automated nucleic acid test, not an AI-powered diagnostic imaging tool that would typically involve human reader interpretation.

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

Yes, the xTAG GPP device's performance was evaluated in a standalone manner. The device performs nucleic acid amplification and detects specific markers, with its inherent software (TDAS GPP (US)) analyzing the data to provide qualitative results (positive/negative) for each pathogen. Human involvement is in sample preparation, loading, and interpreting the final report, but the "performance" data presented (sensitivity, specificity, agreement) directly reflects the algorithm's output compared to ground truth, without a human interpretation step that enhances or modifies the algorithm's initial call. The study assessed the device's ability to detect targets "as determined by the xTAG GPP" against comparator methods.

7. The Type of Ground Truth Used

The ground truth for the test sets was established through a combination of:

• Expert Consensus (Implicit/Composite Comparator): For several analytes (e.g., Norovirus, Rotavirus, ETEC), a "composite comparator method" was used. This involved combining results from multiple individual reference assays (e.g., EIA + PCR/sequencing) and applying specific interpretive algorithms (as detailed for Norovirus) to determine the "true" infection status. This process implicitly relies on expert consensus in defining the gold standard for these complex cases.

• Pathology/Laboratory Methods:

  • Bacterial Culture: For bacterial pathogens like Salmonella, Shigella, Campylobacter, and E. coli O157.
  • Microscopy: For parasites like Cryptosporidium and Giardia.
  • FDA-cleared Assays: For C. difficile (Bartels Cytotoxicity Assay) and some other analytes (e.g., ImmunoCard STAT EHEC for STEC, Premier Rotaclone EIA for Rotavirus).
  • Analytically Validated PCR/Sequencing: Used as a primary comparator for ETEC and for discrepant analysis across many pathogens.

• Outcomes Data: Not explicitly mentioned as a primary method for establishing ground truth, though clinical signs and symptoms were collected and considered in patient selection for the prospective study. The ground truth was primarily based on laboratory detection of the pathogen.

8. The Sample Size for the Training Set

The document does not explicitly specify a "training set" for the xTAG GPP device in the context of machine learning. The device described appears to be a molecular diagnostic assay using pre-defined cut-offs rather than a machine learning algorithm that undergoes a training phase on a dataset.

However, the "Assay cut-off" section mentions that "Clinical specimens, cultured isolates spiked in a synthetic stool matrix sample and extraction controls...were used to establish cut-offs." This process, which involves empirically determining optimal thresholds for MFI values, serves a similar function to model calibration or "training" in traditional statistical modeling.

• Samples used for cut-off establishment: Distinct sample sets comprising clinical specimens with known pathogen status (based on routine diagnostic algorithms), cultured isolates diluted into negative matrix, and extraction controls were used. The precise number of these samples is not explicitly aggregated and labeled as a "training set size."

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

For the "training" data used to establish assay cut-offs (threshold-setting):

• Known Sample Types/Results from Clinical Sites: Samples were assigned a "positive" or "negative" call based on the known sample types or results obtained at the clinical sites. These results were derived from routine diagnostic algorithms (e.g., bacterial culture, EIA/DFA, microscopic examination, real-time PCR, nucleic acid amplification tests followed by bi-directional sequencing).
• Cultured Isolates: Serially diluted cultured isolates with confirmed viral, bacterial, or parasitic identity were used.
• Extraction Controls: Negative matrix spiked with MS2 (internal control) were used and coded as negative for all targets.
• Exclusion Criteria: If comparator results were not available for all 15 targets for a given sample, that target was excluded from the threshold-setting data sets for which its status was unknown.
• Process: The process involved setting an initial cut-off range based on the 95th percentile of negative signals and 5th percentile of positive signals, then recommending optimized cut-offs via Receiver Operating Characteristic (ROC) analysis, and finally establishing the MFI cut-off through a Design Review Committee (DRC) assessment of ROC curves.

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