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The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with the BioCode MDx 3000 Instrument. The BioCode GPP is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites extracted directly from unpreserved stool samples or stool preserved in Cary-Blair transport medium obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria, parasites, and viruses are identified using the BioCode Gastrointestinal Pathogen Panel:

• · Campylobacter (C. jejuni/C. coli)
• · Clostridium difficile (C. difficile) toxin A/B (Fresh samples only)
• · Salmonella spp
• · Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae), including specific identification of Vibrio parahaemolyticus
• · Yersinia enterocolitica
• · Enteroaggregative Escherichia coli (EAEC)
• · Enterotoxigenic Escherichia coli (ETEC) lt/st
• · E. coli 0157 serogroup
• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2
• Shigella/ Enteroinvasive Escherichia coli (EIEC)
• · Cryptosporidium spp (C. parvum/C. hominis)
• Entamoeba histolytica
• · Giardia lamblia (also known as G. intestinalis and G. duodenalis)
• Adenovirus F 40/41
• Norovirus GI/GII
• Rotavirus A

The BioCode GPP is indicated as an aid in the diagnosis of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data.

Positive results do not rule out co-infection with organisms not included in the BioCode GPP. The agent detected may not be the definite cause of the disease. Negative 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.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Adenovirus 40/41, Campylobacter, E. coli 0157, Shigella/EIEC, Yersinia enterocolitica, and Giardia lamblia were established additionally with retrospective clinical specimens. Performance characteristics for Entamoeba histolytica, Giardia lamblia, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and V. cholerae) were established primarily using contrived clinical specimens.

The BioCode Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid-based test designed to be used with the BioCode MDx 3000 system. The BioCode MDx 3000 is an automated system that integrates PCR amplification, target capture, signal generation and optical detection for multiple gastrointestinal pathogens from a single stool specimen, either unpreserved or in Cary Blair. Stool specimens are processed and nucleic acids extracted with the easyMAG and MagNa Pure. Once the PCR plate is set up and sealed, all other operations are automated on MDx 3000. The BioCode MDx 3000 Gastrointestinal Infection Panel simultaneously tests for 17 pathogens (see table below) from unpreserved stool specimens or stool collected in Cary-Blair transport medium. Results from the BioCode Gastrointestinal Pathogen Panel (GPP) test are available within less than 4 hours.

Here's a breakdown of the acceptance criteria and study information for the BioCode Gastrointestinal Pathogen Panel (GPP) as described in the provided document:

Acceptance Criteria and Device Performance for BioCode GPP (with MagNA Pure 96 extraction)

The document focuses on demonstrating the substantial equivalence of the BioCode GPP when used with the MagNA Pure 96 extraction system, compared to its previously cleared version with the easyMAG extraction system (K180041, the predicate device). Therefore, the acceptance criteria and performance are largely derived from the comparison to the existing predicate and the analytical studies.

General Acceptance Criteria (Implied from Clinical Performance Tables):
The acceptance criteria are generally implied to be high positive agreement (PPA) and negative agreement (NPA) with reference methods, typically in the range of 80-100% for PPA and 90-100% for NPA, within a 95% Confidence Interval. For analytical studies, reproducibility is expected to be high (>95%), and the limit of detection (LoD) should be comparable between extraction methods.

Table of Acceptance Criteria and Reported Device Performance (Summary):

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

• Clinical Test Set:

  • Archived Samples: 466 leftover, de-identified samples (275 frozen unpreserved and 191 inoculated Cary-Blair).
    • Provenance: Prospectively collected for the clinical study that resulted in the K180041 BioCode GPP clearance. This suggests the samples were originally collected for diagnostic purposes in a real-world setting, then archived and de-identified for the current study. The country of origin is not explicitly stated but is implied to be within the scope of previous FDA clearance.
  • Fresh Samples: 53 freshly collected leftover samples (specifically for C. difficile testing initially, but used for other targets as well).
    • Provenance: Freshly collected, though the specific clinical sites or countries are not mentioned.
  • Contrived Samples: 120 samples
    • Provenance: Primarily used to establish performance characteristics for Entamoeba histolytica, Giardia lamblia, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and V. cholerae) due to small numbers of naturally positive clinical specimens. These are laboratory-prepared samples.

• Analytical Test Set (Reproducibility Study): Consisted of 7 contrived samples, with combinations of 12 representative targets at 1.5x LoD (Low) and 3x LoD (Medium). Each sample was extracted in triplicate and assayed in singlet. This involved testing across 3 instruments by 3 operators, 2 runs per day for 5 days (total of 30 runs).

• Analytical Test Set (LoD Study):

  • Initial screening: 4 replicates of each concentration (near LoD) in negative stool and Cary-Blair, extracted on both easyMAG and MagNA Pure 96, and tested in singlet.
  • Confirmation: 20 replicates of each sample type/extraction method, tested in singlet, at or near presumptive LoD.
  • Norovirus GI and GII LoD used positive clinical specimens with serial dilutions.

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

The document mentions "Reference methods" which include culture, FDA cleared NAT, PCR/sequencing, and enrichment culture/cleared antigen test. While reference methods are used, the document does not explicitly state the number of experts used to establish the ground truth or their qualifications. It refers to "historical Reference results (K180041)" and "Reference assay". This implies that the ground truth was established by laboratory testing using established diagnostic methods, rather than clinical experts' consensus.

4. Adjudication Method for the Test Set:

The document describes discordant analysis for clinical samples. Specifically, "Sixty-four (64) archived samples with discordant results were retested twice with both easyMag and/or MagNA Pure 96 systems." The retesting appears to be the primary adjudication method. There is no mention of a particular adjudication method like 2+1 or 3+1 involving human experts. The "Comment" section for discordant results often indicates further molecular testing (PCR/Seq) to resolve discrepancies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic test that provides qualitative detection of pathogens. Its performance is evaluated based on its agreement (sensitivity and specificity) with established reference methods, not on how it assists human readers in interpreting images or making diagnoses. Therefore, there is no discussion of human reader improvement with or without AI assistance.

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

Yes, the studies are standalone performance evaluations of the BioCode GPP diagnostic test. The device itself is an automated system that performs nucleic acid extraction, amplification, detection, and decoding to provide qualitative results. The "Clinical Performance" and "Analytical Performance" sections directly assess the accuracy of the device's output against reference methods. There is no human-in-the-loop component in the direct operation or interpretation of the assay results in the way it would apply to, for example, an AI-powered image analysis tool. The results are interpreted by the MDx 3000 system.

7. The Type of Ground Truth Used:

The ground truth for the clinical studies was established using reference laboratory methods, including:

• Culture: For Campylobacter (C. jejuni, C. coli), Escherichia coli (E. coli) 0157, Salmonella, Shigella, Vibrio spp., Yersinia enterocolitica.
• FDA cleared NAT (Nucleic Acid Test): For Clostridium difficile toxin A/B.
• PCR/sequencing: For Adenovirus 40/41, Cryptosporidium (C. parvum, C. hominis), Entamoeba histolytica, Enteropathogenic E. coli (EPEC), Enterotoxigenic E. coli (ETEC) LT/ST, Enteroaggregative E. coli (EAEC), Giardia lamblia /intestinalis, Norovirus GI/GII, Rotavirus A.
• Enrichment culture/cleared antigen test: For Shiga-like Toxin producing E. coli (STEC) stx1/stx2.

Some ground truth for less common organisms (Entamoeba histolytica, Giardia lamblia, Yersinia enterocolitica and Vibrio) was established with contrived clinical specimens, where the pathogen presence and concentration are precisely known.

8. The Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning for an AI device. This is a molecular diagnostic assay, not an AI/ML algorithm that requires training data in the typical sense. The studies presented are primarily for validation and verification of the device's performance. The "K180041 BioCode GPP clearance" mentioned as the source of archived samples suggests previous validation, but that wouldn't necessarily be considered a "training set" for the current device.

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

Since there is no explicit "training set" for an AI/ML algorithm mentioned, this question is not directly applicable. The performance is validated against clinical and analytical studies using reference methods as described in point 7.

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