(90 days)
The BD MAX™ Extended Enteric Bacterial Panel performed on the BD MAX System, is an automated in vitro diagnostic test for the direct qualitative detection and differentiation of enteric bacterial pathogens. It is used in conjunction with the BD MAX Enteric Bacterial Panel as an optional Master Mix. The BD MAX™ Extended Enteric Bacterial Panel detects nucleic acids from
- Plesiomonas shigelloides
- Vibrio (V. vulnificus, V. parahaemolyticus, and V. cholerae)
- Enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin (LT)/ heat-stable ● enterotoxin (ST) genes
- Yersinia enterocolitica ●
Testing is performed on soft to diarrheal unpreserved stool specimens or Cary-Blair preserved stool specimens from symptomatic patients with suspected acute gastroenteritis, enteritis or colitis. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of relevant gene target DNA. The test utilizes fluorogenic gene-specific hybridization probes for the detection of the amplified DNA.
This test is intended for use, in conjunction with clinical presentation, laboratory findings, and epidemiological information, as an aid in the differential diagnosis of Plesiomonas shigelloides, Vibrio (V. vulnificus, V. parahaemolyticus, and V. cholerae), Enterotoxigenic Escherichia coli (ETEC) LT/ST and Yersinia enterocolitica infections. Results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. 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 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.
The BD MAX™ Extended Enteric Bacterial Panel performed on the BD MAX™ System, is an automated in vitro diagnostic test for the direct qualitative detection and differentiation of enteric bacterial pathogens. It is used in conjunction with the BD MAX Enteric Bacterial Panel as an optional Master Mix. The BD MAX Extended Enteric Bacterial Panel detects nucleic acids from
- Plesiomonas shigelloides
- . Vibrio (V. vulnificus, V. parahaemolyticus, and V. cholerae)
- . Enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin (LT)/ heat-stable enterotoxin (ST) genes
- Yersinia enterocolitica
Testing is performed on unpreserved or Cary-Blair preserved soft to diarrheal stool specimens from symptomatic patients with suspected acute gastroenteritis, enteritis or colitis.
The BD MAX™ Extended Enteric Bacterial Panel (BD MAX™ xEBP) is composed of a single Master Mix that must be used in conjunction with the BD MAX™ Enteric Bacterial Panel (BD MAX EBP), performed on the BD MAX™ System. The BD MAX xEBP is performed with the Master Mix contained in the BD MAX xEBP reagent kit and the EBP reagents, including the Master Mix contained in the BD MAX™ EBP reagent kit. The BD MAX xEBP assay and accompanying Assay Definition File (ADF) were developed to allow inclusion of both BD MAX EBP and BD MAX xEBP master mix reagents in one test run.
The BD MAX™ System and the BD MAX™ Extended Enteric Bacterial Panel is run with the instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, extraction reagents, and sample buffer tubes. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, and target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test result may be called as POS (Positive), NEG (Negative), or UNR (Unresolved) for each of the assay's targets, based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAXTM System failure.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for each analyte are not explicitly stated in a single summarized table. However, the performance tables demonstrate the Percentage Positive Agreement (PPA) and Negative Agreement (NPA) for each target organism. A common implicit acceptance criterion for such diagnostic devices is generally a high PPA and NPA, often above 90% for positive and 95% for negative, with a lower bound of the 95% Confidence Interval (CI) also being high.
Here's a summary of the reported device performance, which implies the acceptance criteria were met given the device received clearance:
| Target Organism | Specimen Type | Specimen Origin | BD MAX Performance (PPA (95% CI)) | BD MAX Performance (NPA (95% CI)) |
|---|---|---|---|---|
| Vibrio | Cary-Blair preserved | Prospective (Fresh+Frozen) | 100 (34.2, 100) | 99.6 (99.1, 99.8) |
| Cary-Blair preserved | Retrospective (Frozen) | 100 (34.2, 100) | 100 (80.6, 100) | |
| Unpreserved | Prospective (Fresh+Frozen) | No Data for Calculation | 99.8 (99.2, 99.9) | |
| Unpreserved | Retrospective (Frozen) | 100 (34.2, 100) | 97.8 (88.7, 99.6) | |
| Cary-Blair Preserved | Contrived Samples | 100 (92.6, 100) | 100 (97.4, 100) | |
| Unpreserved | Contrived Samples | 100 (92.6, 100) | 100 (97.4, 100) | |
| Plesiomonas shigelloides | Cary-Blair preserved | Prospective | No Data for Calculation | 99.9 (99.5, 100) |
| Cary-Blair preserved | Retrospective | 100 (51, 100) | 100 (90.8, 100) | |
| Unpreserved | Prospective | No Data for Calculation | 99.9 (99.3, 100) | |
| Unpreserved | Retrospective | 100 (43.9, 100) | 97.9 (88.9, 99.6) | |
| Cary-Blair Preserved | Contrived Samples | 100 (92.6, 100) | 100 (97.4, 100) | |
| Unpreserved | Contrived Samples | 100 (92.6, 100) | 99.3 (96.2, 99.9) | |
| Yersinia enterocolitica | Cary-Blair preserved | Prospective | No Data for Calculation | 99.9 (99.6, 100) |
| Cary-Blair preserved | Retrospective | No Data for Calculation | 100 (89.3, 100) | |
| Unpreserved | Prospective | No Data for Calculation | 100 (99.6, 100) | |
| Unpreserved | Retrospective | 100 (70.1, 100) | 100 (92.4, 100) | |
| Cary-Blair Preserved | Contrived Samples | 97.9 (89.1, 99.6) | 100 (97.4, 100) | |
| Unpreserved | Contrived Samples | 100 (92.6, 100) | 100 (97.4, 100) | |
| ETEC (LT/ST) | Cary-Blair preserved | Prospective | 100 (72.2, 100) | 99.8 (99.3, 99.9) |
| Cary-Blair preserved | Retrospective | 100 (56.6, 100) | 100 (87.9, 100) | |
| Unpreserved | Prospective | 100 (80.6, 100) | 99.9 (99.3, 100) | |
| Unpreserved | Retrospective | 90 (59.6, 98.2) | 96.3 (81.7, 99.3) |
2. Sample Size Used for the Test Set and Data Provenance
- Total Clinical Specimens: 2410 specimens were enrolled.
- Prospective: 2264 specimens (882 unpreserved, 1382 Cary-Blair preserved)
- Retrospective: 146 specimens (87 unpreserved, 59 Cary-Blair preserved)
- Compliant Clinical Specimens: 2403 specimens were compliant.
- Contrived Samples:
- Vibrio: 192 (48 positive, 144 negative) for both Cary-Blair preserved and unpreserved, totaling 384 contrived samples.
- Plesiomonas shigelloides: 192 (48 positive, 144 negative) for both Cary-Blair preserved and unpreserved, totaling 384 contrived samples.
- Yersinia enterocolitica: 192 (48 positive, 144 negative) for both Cary-Blair preserved and unpreserved, totaling 384 contrived samples.
- Data Provenance: The prospective specimens were collected as part of routine patient care from six (6) geographically diverse clinical centers (multi-site investigational study), implying data from various locations. The retrospective specimens' historical results were recorded at the collection site. The study involved patients from different age groups from 0-1 month to Over 21 years old. The specific country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the study sites were likely within the US or compliant with US regulatory standards.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with X years of experience) used to establish the ground truth.
4. Adjudication Method (for the test set)
- For prospective fresh and prospective frozen specimens, the reference method for bacterial culture (Yersinia enterocolitica, Vibrio, and Plesiomonas shigelloides) was followed by alternate PCR assay and bi-directional sequencing on presumptive positive isolates.
- For ETEC, the comparator method was two alternate PCR assays and bidirectional sequencing performed directly from stool specimens.
- For retrospective specimens, the historical results were confirmed using an alternate PCR assay and bi-directional sequencing as part of the composite comparator method.
- Discrepant Analysis: For discrepant results (BD MAX result differed from the reference method), "discordance study" was performed, which involved retesting. The details imply that sequencing was used to resolve discrepancies.
The method can be described as a composite reference standard or adjudicated reference standard combining culture, alternative PCR, and bi-directional sequencing, with further investigation for discrepant cases. There is no explicit mention of an "N+1" method with human readers reviewing cases in the traditional sense of imaging studies.
5. If a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study involving human readers improving with AI vs. without AI assistance was not conducted. This is an IVD (In Vitro Diagnostic) device, not an imaging AI device that typically involves human interpretation. The study is focused on the device's analytical and clinical performance against a reference standard.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the clinical performance study evaluated the device in a standalone manner. The BD MAX™ Extended Enteric Bacterial Panel (an automated in vitro diagnostic test) was performed, and its results were compared directly against the reference method. There is no mention of human-in-the-loop performance influencing the assay's output during the clinical evaluation. The system automates sample preparation, DNA extraction, amplification, and interpretation.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth was established using a composite reference standard:
- For Yersinia enterocolitica, Vibrio, and Plesiomonas shigelloides: Bacterial culture followed by alternate PCR assay and bi-directional sequencing on presumptive positive isolates.
- For ETEC: Two alternate PCR assays and bidirectional sequencing performed from stool specimens.
- For retrospective samples: Confirmation of historical results using alternate PCR assay and bi-directional sequencing.
This is best categorized as a laboratory-based composite reference standard combining different microbiological and molecular techniques.
8. The sample size for the training set
The document does not explicitly state the sample size used for a "training set." The performance studies described are for the analytical and clinical validation of the device, typically representing a test or validation set after development. The analytical studies (e.g., LoD, inclusivity, cross-reactivity) involve testing various strains and concentrations to characterize the device. These are often used for optimizing the assay during development, but a distinct "training set" in the context of machine learning model development is not specified.
9. How the ground truth for the training set was established
Since a dedicated "training set" is not explicitly detailed in the provided K170308 summary, the method for establishing its ground truth is also not described. The analytical studies describe preparing known positive and negative samples using quantified cultures and negative fecal matrix, which would serve a similar function to generating truth data for assay development and validation.
§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.
(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a 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 and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).