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The BD MAX Enteric Parasite Panel performed on the BD MAX System is an automated in vitro diagnostic test for the direct qualitative detection of enteric pathogens. The BD MAX Enteric Parasite Panel detects nucleic acids from:
Giardia lamblia
Cryptosporidium (C. hominis and C. parvum only), Entamoeba histolytica
Testing is performed on unpreserved or 10% formalin-fixed stool specimens from symptomatic patients with suspected gastroenteritis, or colitis. The assay is intended to aid in the diagnosis of gastrontestinal infection when used in conjunction with clinical evaluation and other laboratory findings. The test is performed directly on the specimen, utilizing real- time polymerase chain reaction (PCR) for the amplification of specific targets. The test utilizes fluorogenic gene-specific hybridization probes for 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 Giardia lamblia, Cryptosporidium hominis, and C. parvum, as well as Entamoeba histolytica infections. Results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decision. 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 and/or colitis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as colitis, irritable bowel syndrome, or Crohn's disease.

The BD MAX™ Enteric Parasite Panel assay along with the BD MAX™ System are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges. master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis. DNA extraction and concentration, reagent rehydration, 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 results. For the BD MAX™ Enteric Parasite Panel, a test result may be called POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAXTM System failure.

The provided text describes the BD MAX™ Enteric Parasite Panel, a diagnostic test for detecting specific parasitic nucleic acids in stool samples. The submission K220193 is a 510(k) premarket notification to add the Copan FecalSwab™ Collection, Preservation, and Transport System as an acceptable specimen type for use with the existing BD MAX™ Enteric Parasite Panel (predicate device K143648).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

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

The document does not explicitly state acceptance criteria in a table format with associated performance for the FecalSwab addition. Instead, it describes a series of studies designed to demonstrate that the performance of the device with FecalSwab specimens is equivalent or comparable to its performance with existing (unpreserved) specimen types. The core acceptance criterion for this submission is that the FecalSwab specimens perform similarly enough to unpreserved specimens to be considered "substantially equivalent."

Here's a summary of the reported performance from the studies aiming to demonstrate this equivalence:

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

The document provides very limited detail on specific sample sizes for the test sets.

• Analytical Sensitivity (LoD) Study: Not specified, but generally, LoD studies involve testing multiple replicates at various concentrations.
• Stability Study: Not specified, but implies a sufficient number of samples across different storage conditions and time points to achieve > 95% detection.
• User Variability Study: Not specified, but involved multiple users preparing FecalSwab tubes.
• Clinical Performance Comparison Study: "retrospectively collected clinical specimens." The exact number of specimens is not provided.
  • Data Provenance: Retrospective clinical specimens. The country of origin is not specified.

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 in the document. The studies described are primarily analytical and comparative evaluations of specimen types rather than diagnostic performance against a clinical ground truth established by experts. For the clinical comparison study, "retrospectively collected clinical specimens" were used, implying their original diagnostic status (positive/negative for specific parasites) served as a de facto ground truth, likely established by previous standard diagnostic methods or a combination of clinical and laboratory findings. No specific mention of experts or their qualifications for establishing this ground truth is made for this set of studies.

4. Adjudication method for the test set

The document does not mention any adjudication method. Since the studies focus on comparing a new specimen type to an existing one, the "truth" for the samples (especially in analytical studies) would be based on the known concentration of spiked organisms or the pre-established diagnostic status of clinical samples.

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 involving human readers and AI assistance was not done. This device is a molecular diagnostic test (PCR-based), not an AI-powered image analysis or interpretation tool that would involve human readers.

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

Yes, this can be considered a standalone performance evaluation of the assay. The BD MAX™ System "automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR." The "software automatically interprets test results." There is no "human-in-the-loop" for the interpretation of the PCR results themselves beyond potentially reviewing unresolved or indeterminate results as per laboratory protocols. The studies evaluate the analytical and clinical performance of the automated system with different specimen inputs.

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

The ground truth used depends on the specific study type:

• Analytical Sensitivity (LoD): Likely based on known concentrations of target organisms spiked into fecal matrix, representing a quantitative "ground truth."
• Stability Study: Similar to LoD, based on known concentrations of spiked organisms.
• User Variability Study: Also likely based on known spiked concentrations in prepared samples.
• Clinical Performance Comparison: The ground truth for the retrospectively collected clinical specimens would be their pre-established diagnostic status, which would typically arise from standard of care laboratory methods (e.g., microscopy, culture, or other molecular tests) and clinical presentation at the time of original diagnosis. The document states "performance of the BD MAX™ Enteric Parasite Panel assay with the FecalSwab specimen type is comparable to the unpreserved stool specimen type," implying the original diagnosis on the unpreserved samples (or the consensus of prior methods) served as the comparator.

8. The sample size for the training set

The document does not specify a training set sample size. This submission is for an updated specimen claim for an existing device (BD MAX™ Enteric Parasite Panel, K143648), not the initial development or de novo training of the core algorithm. The studies conducted here are primarily validation/verification studies for the FecalSwab specimen type.

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

Since no specific training set is mentioned for this particular submission (K220193), the method for establishing ground truth for a training set is not applicable to the information provided. The original predicate device (K143648) would have undergone its own development and validation, which would have involved establishing ground truth for its analytical and clinical studies.

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The BD MAX™ Enteric Parasite Panel performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct qualitative detection of enteric pathogens. The BD MAX Enteric Parasite Panel detects nucleic acids from:
• Giardia lamblia

• · Cryptosporidium (C. hominis and C. parvum only)
• Entamoeba histolytica
  Testing is performed on unpreserved or 10% formalin-fixed stool specimens from symptomatic patients with suspected gastroenteritis, enteritis or colitis. The assay is intended to aid in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of specific targets. The test utilizes fluorogenic gene-specific hybridization probes for 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 Giardia lamblia, Cryptosporidium hominis and C. parvum, as well as Entamoeba histolytica infections. Results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decision. 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 ss compatible with gastroenteritis and/or colitis 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™ System and the BD MAX™ Enteric Parasite Panel are comprised of an 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 results. A test result may be called as POS, NEG or UNR 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 MAX™ System failure.

The provided document describes the analytical and clinical performance of the BD MAX™ Enteric Parasite Panel, an in vitro diagnostic test. The acceptance criteria and device performance are outlined in the "Clinical Performance Studies" section.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for the clinical performance endpoints in a single, clear table. However, the reported performance metrics (Sensitivity, Specificity, PPA, NPA) for each target and specimen type are presented. For the purpose of this response, I will interpret the reported performance values themselves as the "device performance" and highlight the key metrics that would typically serve as acceptance criteria in such a submission.

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

• Total Compliant Specimens: 2495 (1273 10% formalin-fixed, 1222 unpreserved).
• Split by Type:
  • Prospective: 2204 specimens (1128 10% formalin-fixed, 1058 unpreserved, 18 noncompliant - excluded).
  • Retrospective: 411 specimens (148 10% formalin-fixed, 251 unpreserved, 12 noncompliant - excluded).
  • Excluded from Performance Calculations: 128 retrospective specimens (historical results not confirmed by alternate PCR and bi-directional sequencing).
• Adjusted Compliant Specimens for Performance:
  • Giardia lamblia: 1021 (10% Formalin-Fixed Prospective), 126 (10% Formalin-Fixed Retrospective), 673 (Unpreserved Prospective), 209 (Unpreserved Retrospective)
  • Cryptosporidium parvum/hominis: 1015 (10% Formalin-Fixed Prospective), 121 (10% Formalin-Fixed Retrospective), 663 (Unpreserved Prospective), 228 (Unpreserved Retrospective)
  • Entamoeba histolytica: 827 (10% Formalin-Fixed Prospective), 54 (10% Formalin-Fixed Retrospective), 577 (Unpreserved Prospective), 202 (Unpreserved Retrospective)
  • Entamoeba histolytica (Contrived): 100 (50 10% formalin-fixed, 50 unpreserved)
• Data Provenance: The study was a multicenter clinical study with specimens collected as part of routine patient care. It involved five (5) clinical sites and seven (7) collection sites. An internal site also performed testing on specimens from collection centers. The data includes both prospective and retrospective specimens. The country of origin of the data is not explicitly stated, but given the FDA submission, it is likely primarily from the USA, though multi-site studies can include international sites.

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

The document describes a "reference method" for establishing ground truth, but does not specify the number or qualifications of experts (e.g., medical technologists, pathologists, or specific specialists) involved in establishing the ground truth.

The "reference method" included:

• Standard microscopic examination (possibly O&P, though not explicitly named as the sole method).
• For confirmed positive specimens, an "alternate PCR and bi-directional sequencing" was used.
• For Giardia lamblia and Cryptosporidium, DFA (Direct Fluorescent Antibody) was also part of the reference method.
• Discrepant analysis involved repeat testing with the alternate PCR and bi-directional sequencing, DFA, EIA (Enzyme Immunoassay), and repeat testing with the BD MAX™ Enteric Panel.

4. Adjudication Method for the Test Set

The document details a discrepant resolution process for the clinical study:

• For specimens where the BD MAX Enteric Parasite Panel result differed from the initial reference method, "discrepant repeat testing" was performed.
• This repeat testing included:
  • Alternate PCR and bi-directional sequencing.
  • DFA (for Giardia and Cryptosporidium).
  • EIA (for Giardia).
  • Repeat testing with the BD MAX™ Enteric Panel (often in multiple replicates, e.g., 6 or 12 replicates).

This indicates an adjudication method that goes beyond a simple "x+1" or "x+y" rule, involving multiple different assays and follow-up analysis to establish a confirmed ground truth, particularly for discrepant results. It's a method driven by discrepancy rather than a fixed "consensus" rule initially.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not mentioned or performed. This device is an automated molecular diagnostic test and does not involve human "readers" in the interpretation of results in the way an imaging AI device would. The BD MAX System itself automates the interpretation of test results.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, this entire study can be considered a standalone performance evaluation. The BD MAX™ Enteric Parasite Panel is an automated in vitro diagnostic test, and its performance was evaluated against a reference method (ground truth) without a human-in-the-loop component for the device's operation or result interpretation. The "Test Principle" section explicitly states, "The BD MAX™ System software automatically interprets test results. A test result may be called as POS, NEG or UNR for each of the assay's targets..."

7. Type of Ground Truth Used

The ground truth for the clinical studies was established using a composite reference method consisting of:

• Microscopic examination (implied, given the nature of parasite detection tests, though not explicitly detailed for all cases).
• Alternate PCR and bi-directional sequencing: This is a highly specific molecular method for confirming the presence and identity of the target pathogens.
• Direct Fluorescent Antibody (DFA): Used for Giardia and Cryptosporidium.
• Enzyme Immunoassay (EIA): Used in discrepant analysis for Giardia.

For Entamoeba histolytica, given its rarity, contrived specimens (spiked residual negative clinical specimens) were also used to supplement clinical data for evaluating positive percent agreement.

8. Sample Size for the Training Set

The document does not explicitly state a sample size for a "training set" in the context of machine learning or algorithm development. This device is a real-time PCR assay, and its performance is based on the specificity of its primers and probes and the robustness of the extraction and amplification process, rather than a machine learning model that requires a distinct training set. The "Analytical Inclusivity" and "Analytical Specificity" sections describe testing against known strains and related organisms, which could be considered akin to "training" or "development" data for assay design, but not "training set" in the common AI/ML sense.

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

As there's no explicitly defined "training set" in the AI/ML sense, there's no ground truth established in that context. However, for the analytical studies (e.g., Limit of Detection, Inclusivity, Specificity), the ground truth was established by:

• Known concentrations of purified organisms: For LoD, organisms were inoculated at specific concentrations into negative stool matrix.
• Known strains/isolates: For inclusivity, specific ATCC strains or known clinical isolates of the target organisms were used.
• Known phylogenetically related species and other organisms: For specificity, a wide range of known bacteria, viruses, parasites, and yeast were tested at specified concentrations.

This involves laboratory-controlled methods, where the "ground truth" (presence/absence and concentration of a specific organism) is inherently known by design.

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