Search Results

The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism.

The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB.

The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease.

The ePlex BCID-GP Panel also contains targets designed to detect a broad range of organisms with a potentially misleading Gram stain result or organisms that may be missed by Gram staining altogether, for example in the case of co-infections. These include a broad Pan Gram-Negative assay as well as a Pan Candida assay, which is designed to detect four of the most prevalent Candida species: Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis.

The detection and identification of specific bacterial and fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-GP Panel are intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a suspected bloodstream infection may be due to infection with pathogens that are not detected by this test. Positive results do not rule out co-infection with other organisms; the organism(s) detected by the ePlex BCID-GP Panel may not be the definite cause of disease. Additional laboratory testing (e.g. sub-culturing of positive blood cultures for identification of organisms not detected by ePlex BCID-GP Panel and for susceptibility testing. differentiation of mixed growth and association of antimicrobial resistance marker genes to a specific organism) and clinical presentation must be taken into consideration in the final diagnosis of blood stream infection.

The ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is based on the principles of competitive nucleic acid hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to a sequence-specific solution-phase signal probe and a solid-phase electrode-bound capture probe. The test employs nucleic acid extraction, target amplification via polymerase chain reaction (PCR) or reverse transcription PCR (RT-PCR) and hybridization of target DNA. In the process, the double-stranded PCR amplicons are digested with exonuclease to generate single-stranded DNA suitable for hybridization.

Nucleic acid extraction from biological samples occurs within the cartridge via cell lysis, nucleic acid capture onto magnetic beads, and release for amplification. The nucleic acid extraction is processed through microfluidic liquid handling. Once the nucleic acid targets are captured and inhibitors are washed away, the magnetic particles are delivered to the electrowetting environment on the printed circuit board (PCB) and the targets are eluted from the particles and amplified.

During hybridization, the single-stranded target DNA binds to a complementary, single-stranded capture probe immobilized on the working gold electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to specific target sequence / region adjacent to the capture probe. Simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each working electrode on the array contains specific capture probes, and sequential analysis of each electrode allows detection of multiple analyte targets.

Here's an analysis of the provided text to extract information about the device's acceptance criteria and the study proving it meets them.

The document is a 510(k) Premarket Notification from the FDA regarding the GenMark ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel (K181663). The core of the performance data revolves around clinical performance (sensitivity/PPA and specificity/NPA) against comparator methods, and analytical performance (Limit of Detection, Inclusivity, Exclusivity, Reproducibility, Interfering Substances, Competitive Inhibition).

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the clinical and analytical performance targets the device aimed to meet, typically demonstrating non-inferiority or substantial equivalence to a predicate device and adequate analytical performance. The tables provided (Table 6 through Table 30 for clinical performance, and Table 61 onwards for reproducibility) present the device's reported performance. A formal table of acceptance criteria with corresponding results isn't explicitly laid out with a "criteria" column alongside "performance" in the document, but we can infer the criteria from the achieved results and the FDA clearance itself, which implies acceptable performance.

For this device, the primary acceptance criteria would be high Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with established comparator methods for all targeted organisms and resistance genes, along with robust analytical performance.

Here's a summary of the reported performance, reflecting the device meeting implicit acceptance criteria for clinical accuracy:

Table 1: Derived Acceptance Criteria and Reported Device Performance (Selected Examples)

Detailed Information about the Study:

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

   • See the table above for inferred criteria and reported performance based on clinical PPA/NPA. The acceptance criteria are not explicitly stated as quantitative thresholds in the provided text, but the successful clearance of the device implies that the observed performance was deemed acceptable by the FDA.

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

   • Test Set (Clinical Study):
     • Prospective Samples: Total 711 evaluable samples. Collected from 7 clinical sites. 312 were tested fresh (Jan-Feb 2018), and 399 were frozen (June 2014-July 2016).
     • Retrospective Samples: Total 586 evaluable samples. Collected to supplement low prevalence targets.
     • Combined Clinical Samples: 1297 (711 prospective + 586 retrospective).
     • Contrived Samples: 565 samples prepared by spiking isolates into blood culture bottles.
   • Data Provenance: The document states "A prospective, multicenter clinical study was conducted at 7 clinical sites." While specific countries are not mentioned, FDA clearances typically involve studies predominantly conducted in the USA or with data acceptable to US regulatory standards. The terms "multicenter" and "clinical sites" imply different geographical locations although not explicitly named.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

   • The ground truth for the clinical test set was established using "Standard laboratory procedures" including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques for organism identification. Specific PCR assays followed by bi-directional sequencing (or 16S sequencing for Corynebacterium, Staphylococcus epidermidis, Candida parapsilosis) were used for confirmation where necessary. For antibiotic resistance genes (mecA, mecC, vanA, vanB), ground truth was established using analytically validated qPCR amplification assays followed by bi-directional sequencing.
   • The document does not specify the number of experts or their qualifications (e.g., board-certified microbiologists, medical technologists with X years of experience) who performed these standard laboratory procedures or interpreted the sequencing results to establish ground truth.

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

   • The document describes a comparison between the ePlex BCID-GP Panel results and "comparator method(s) results." For discrepant results (e.g., false positives, false negatives), additional analytically validated PCR assays and sequencing were used for confirmation (e.g., for Corynebacterium, S. epidermidis, Pan Candida, Staphylococcus for mecA, and Enterococcus for vanA/vanB).
   • This is a form of adjudication, where discrepant results are further investigated. However, it's not a multi-reader adjudication method (like 2+1, 3+1) involving multiple human readers interpreting results, as this device performs automated detection. Instead, it's a discrepancy resolution method using a higher-level, analytically validated diagnostic test (PCR/sequencing) as the tie-breaker/confirmatory method.

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, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic test for identifying microorganisms and resistance markers, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Its performance is evaluated against laboratory standard reference methods, not against human reader performance or improvement with AI assistance.

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

   • Yes, the primary clinical and analytical performance studies are standalone (algorithm only) performance. The ePlex BCID-GP Panel is an automated test on the ePlex Instrument. Its results are generated by the device's assay and software, and then compared directly to the ground truth established by comparator laboratory methods. There is no explicit human-in-the-loop component described for its diagnostic performance evaluation, although clinical interpretation of the results by medical professionals is clearly indicated as necessary for patient management decisions (as stated in the Indications for Use).

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

   • The ground truth for the clinical study was based on "Standard laboratory procedures" for organism identification (culture, MALDI-TOF IVD, microbiological/biochemical techniques) and analytically validated PCR assays with bi-directional sequencing for confirmation of specific organisms and all resistance genes. This would fall under laboratory reference standard/molecular confirmation. Clinical outcomes data was not primarily used for ground truth.

8. The sample size for the training set

   • The document does not specify a separate "training set" size for the development of the ePlex BCID-GP Panel's algorithm. For in vitro diagnostic devices like this one, the development process might involve internal validation and optimization, but the regulatory submission focuses on the performance of the final, locked version of the device using a clinically representative "test set." The text primarily describes the clinical evaluation (prospective, retrospective, contrived samples) which serves as the independent test set for regulatory submission.

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

   • As a distinct "training set" is not explicitly mentioned as per typical machine learning contexts, the document doesn't detail how ground truth for such a set was established. It's plausible that internal development and optimization would have used similar laboratory reference methods as those used for the clinical validation.

Ask a specific question about this device