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The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• · Bacterial vaginosis markers (Individual markers not reported)
  Lactobacillus spp. (L. crispatus and L. jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) Megasphaera-1
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• Candida glabrata
• Candida krusei
• Trichomonas vaginalis
  The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis.

The BD MAX System and the BD MAX Vaginal Panel 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 Vaginal Panel, a test result may be called as 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 MAX System failure.

This document describes the 510(k) premarket notification for the BD MAX Vaginal Panel for use with the BD MAX System. The purpose of this submission is to demonstrate the substantial equivalence of the modified device, particularly the BD Molecular Swab Collection Kit, to its predicate device, the BD MAX Vaginal Panel (DEN160001 and K191957) which used the BD MAX UVE Specimen Collection Kit.

Here's an analysis of the acceptance criteria and supporting studies based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text focuses on demonstrating the substantial equivalence of the collection kit for an already cleared device, rather than establishing initial performance for a novel diagnostic device. Therefore, explicit acceptance criteria in terms of sensitivity, specificity, PPV, and NPV for the BD MAX Vaginal Panel itself are not directly stated in this section, as those would have been established during the original clearances (DEN160001 and K191957).

However, the performance is evaluated in comparison to the predicate's collection kit. The reported performance for the comparison study between the cleared collection device (BD MAX UVE Specimen Collection Kit) and the new collection device (BD Molecular Swab Collection Kit) demonstrated the following:

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

• Sample Size for Comparison Study: The document states that a "comparison study of performance between the cleared collection device and the new collection device tested with the BD MAX Vaginal Panel on the BD MAX System with clinical specimens" was conducted. However, the exact number of clinical specimens used in this comparison study is not explicitly provided in the text.
• Data Provenance: The data used for the comparison study are from "clinical specimens." The country of origin is not specified, and it is stated as a retrospective or prospective study.

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

The document does not describe the establishment of a ground truth by experts for the comparison study of the collection kits. For molecular diagnostic assays like the BD MAX Vaginal Panel, the "ground truth" for the original device's performance validation is often established using methods such as:

• Culture: For culturable organisms like Candida species or Trichomonas vaginalis.
• Microscopy (e.g., Amsel's criteria, Nugent scoring): For bacterial vaginosis.
• Reference molecular methods: For organisms difficult to culture or quantify.

Since the focus here is on the collection kit equivalence, the ground truth would inherently refer to the original diagnostic results obtained using the predicate device's collection kit, which are then compared to the results from the new collection kit. The text does not mention any independent expert panel establishing ground truth specifically for these comparison studies.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (such as 2+1, 3+1, or none) for the test set used in the comparison study. The comparison is between the performance of two collection kits with the same diagnostic panel, suggesting a direct comparison of results rather than an adjudication process involving multiple human readers to establish a reconciled truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for imaging or interpretation tasks where human readers play a significant role. The BD MAX Vaginal Panel is an automated in vitro diagnostic test, and its results are interpreted by the BD MAX System software, not human readers in a diagnostic capacity that would warrant an MRMC study.

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

Yes, the BD MAX Vaginal Panel operates as a standalone (algorithm-only) device. The device description explicitly states: "The BD MAX System software automatically interprets test results." There is no human-in-the-loop performance described for the interpretation of the test results themselves. The studies confirm the analytical and clinical performance of the automated system with the new collection kit.

7. The Type of Ground Truth Used

For the comparison study, the "ground truth" for evaluating the new collection kit's performance would implicitly be the results obtained when the same clinical specimens were tested using the predicate device's collection kit (BD MAX UVE Specimen Collection Kit) with the BD MAX Vaginal Panel. This is because the study aims to show the collections kits are equivalent and the performance of the BD MAX Vaginal Panel is already established with the predicate kit.

The initial ground truth for the diagnostic panel itself (BD MAX Vaginal Panel, cleared as DEN160001 and K191957) would have been established through a combination of:

• Clinical diagnosis and criteria: For example, Amsel's criteria or Nugent score for bacterial vaginosis, or clinical signs and symptoms for vaginitis.
• Culture: For culturable pathogens.
• Reference molecular methods: For specific DNA targets.

8. The Sample Size for the Training Set

The document does not provide information regarding a "training set" or its sample size. This is typical for an IVD device submission that is demonstrating substantial equivalence of a component (collection kit) for an already cleared diagnostic system. The algorithms for the BD MAX System and the Vaginal Panel would have been developed and "trained" (in a broad sense of model development) prior to the original 510(k) clearances (DEN160001 and K191957). This document does not detail the development phase of the assay.

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

As no training set is discussed in this document, the method for establishing its ground truth is also not described. As mentioned above, the development and establishment of ground truth for the original assay would have occurred during its prior 510(k) clearances.

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The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direction of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Bacterial vaginosis markers (Individual markers not reported)
  Lactobacillus spp. (L. crispatus and L. jensenii) Gardnerella vaginalis Atopobium vaginae Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) Megasphaera-1
• . Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis)
• Candida glabrata
• Candida krusei
• . Trichomonas vaginalis

The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD MAX System and the BD MAX Vaginal Panel 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 Vaginal Panel, a test result may be called as 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 MAX System failure.

This is an FDA 510(k) summary for the BD MAX Vaginal Panel for detecting microorganisms associated with vaginitis and bacterial vaginosis. The document describes the device, its intended use, and its equivalence to a predicate device. While it mentions performance standards, it does not contain detailed acceptance criteria, device performance data, information on the study design (sample size, data provenance, ground truth establishment, expert qualifications, adjudication methods), or any multi-reader multi-case (MRMC) study results.

Therefore, many of the requested fields cannot be filled from the provided text.

Here's a breakdown of what can be extracted and what is missing:

1. Table of acceptance criteria and the reported device performance:

• Acceptance Criteria: Not explicitly stated in terms of specific performance metrics (e.g., sensitivity, specificity, accuracy thresholds). The document broadly refers to "Performance Standards" based on the Class II Special Controls Guideline for NAAT assays for Trichomonas vaginalis.
• Reported Device Performance: Not provided in this document. This summary focuses on substantial equivalence based on technological characteristics and intended use.

2. Sample size used for the test set and the data provenance: Not mentioned.

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): Not mentioned.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not mentioned.

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: Not applicable. This is a molecular diagnostic test, not an AI-assisted imaging device or a test involving human readers in the interpretation loop.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done: The device is a standalone molecular diagnostic assay. The results are "automatically interpreted" by the BD MAX System software, which indicates algorithm-only performance. However, specific standalone performance metrics (sensitivity, specificity etc.) are not provided.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc): Not mentioned for the studies supporting this 510(k) submission. For molecular tests, ground truth typically involves culture or a validated composite reference method.

8. The sample size for the training set: Not mentioned.

9. How the ground truth for the training set was established: Not mentioned.

Summary Table of Available Information:

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The BD MAX Vaginal Panel performed on the BD MAX System is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• Bacterial vaginosis markers (Individual markers not reported)
  • O Lactobacillus spp. (L. crispatus and L. jensenii)
  • Gardnerella vaginalis о
  • o Atopobium vaginae
  • Bacterial Vaginosis Associated Bacteria-2 (BVAB-2) o
  • o Megasphaera-1
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis) ●
• Candida glabrata
• Candida krusei ●
• Trichomonas vaginalis

The BD MAX Vaginal Panel is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

The BD MAX System and the BD MAX Vaginal Panel 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 Vaginal Panel, a test result may be called as 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 MAX System failure.

Acceptance Criteria and Study for BD MAX Vaginal Panel

The BD MAX Vaginal Panel is an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in symptomatic patients. The device's performance was evaluated through a prospective clinical study and various analytical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are not explicitly stated as distinct numerical thresholds in the provided document for all metrics. Instead, the document presents detailed performance characteristics from various studies, implying that the observed performance was acceptable for De Novo classification. For the purpose of this response, I will infer "acceptance criteria" where possible from general regulatory expectations for diagnostic devices and the context of the reported results (e.g., successful detection, high agreement). The "Reported Device Performance" will reflect the results from the clinical and analytical studies.

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

Test Set (Clinical Study):

• Total subjects enrolled: 1763
• Compliant subjects: 1740
• Compliant specimens with reportable results:
  • Bacterial Vaginosis: 1559 (clinician-collected), 1582 (self-collected)
  • Candida: 1618 (clinician-collected), 1628 (self-collected)
  • Trichomonas vaginalis: 1600 (clinician-collected), 1610 (self-collected)
• Asymptomatic Women (separate evaluation): 202 women
• Contrived Specimens for C. glabrata and C. krusei: 50 strains each, developed at various concentrations, plus 50 true negative specimens for each organism.

Data Provenance:

• The data for the primary clinical study was prospective.
• Specimen collection occurred at 10 geographically diverse specimen collection sites. Seven sites performed collection only, and three performed both collection and testing with the BD MAX Vaginal Panel. (The country of origin is not explicitly stated but is implicitly the US given FDA submission context).
• Analytical studies (Precision, LoD, Inclusivity, Interference, Stability, Specificity) used simulated vaginal matrix and/or natural negative vaginal matrix, and commercially available organisms/plasmid DNA.

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

The document specifies the reference methods used to establish ground truth but does not explicitly state the number or qualifications of experts involved in the interpretation of these reference methods.

• BV status: Determined using a combination of Nugent Score and Amsel's criteria. These methods typically involve microscopic evaluation by trained laboratory personnel or clinicians, but specific expert qualifications (e.g., years of experience, specific certifications) are not detailed.
• Candida spp. status: Determined by selective (Candida) chromogenic medium and Sabouraud Dextrose Emmons plate cultures. PCR amplification targeting the its2 gene was performed followed by bi-directional sequencing to identify yeast isolates. Interpretation of cultures and sequencing results would be performed by trained microbiologists or laboratory specialists.
• Trichomonas vaginalis status: Determined by a composite of microscopic visualization of motile trichomonads in saline wet mounts of vaginal secretion and by culture. A positive result by either method categorized the patient as positive. Microscopic visualization implies examination by trained personnel.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for discordant results between the reference methods themselves or between the device and reference methods.

• For BV, "Specimens with normal flora as per the Nugent Score were considered negative: those positive for BV flora were considered positive while those with intermediate BV flora were segregated into positive or negative categories using Amsel's criteria." This implies a defined algorithm for combining the reference standards rather than a separate expert adjudication panel.
• For Trichomonas vaginalis, "A positive result either by wet mount or by culture was sufficient to categorize the patient as positive." This constitutes a composite reference standard.
• For analyses of discordant results (e.g., for T. vaginalis false negatives and false positives, or C. glabrata false negatives), the document mentions further evaluation with an "FDA-cleared molecular method" or assessing growth levels from chromagar, which indicates further diagnostic investigation rather than expert consensus adjudication of initial reference results.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an automated, standalone molecular diagnostic test. It does not involve human readers interpreting images or data to make a diagnosis that would then be compared with and without AI assistance. Therefore, there is no effect size reported for human readers improving with vs. without AI assistance.

6. Standalone Performance Study

Yes, a standalone (i.e., algorithm only without human-in-the-loop performance) was done. The entire premise of the clinical and analytical studies is to evaluate the BD MAX Vaginal Panel's performance on its own, comparing its direct output (qualitative detection of DNA targets) to established reference methods. The system automates sample preparation, DNA extraction, amplification, detection, and interpretation of test results (POS, NEG, or UNR). The clinical performance metrics (sensitivity, specificity, PPV, NPV) presented in Tables 17-36 represent the standalone performance of the device.

7. Type of Ground Truth Used

The ground truth used for the clinical study was a composite reference standard:

• Bacterial Vaginosis: A combination of Nugent Score and Amsel's criteria.
• Candida spp.: Culture (chromogenic medium and Sabouraud Dextrose Emmons plate cultures) followed by PCR amplification targeting the its2 gene and bi-directional sequencing for species identification.
• Trichomonas vaginalis: A composite of microscopic visualization of motile trichomonads in saline wet mounts of vaginal secretion and culture.

This approach combines multiple diagnostic methods to establish the most accurate possible "true" status for each patient's sample.

8. Sample Size for the Training Set

The document does not explicitly state the sample size for a separate "training set" in the context of machine learning or AI model development. The BD MAX Vaginal Panel is described as a nucleic acid-based test utilizing real-time PCR with fluorogenic target-specific hybridization probes, and software for automated interpretation based on amplification status. While there's an "Assay Cut-off" section mentioning use of pre-clinical studies and prospective clinical study data to "validate these cut-offs" and "ROC curve analysis was performed to confirm the optimal cutoffs," this typically refers to refining analytical thresholds based on observed performance from early testing rather than training a complex AI model in the conventional sense.

The "pre-clinical studies" and "LoD confirmation study" using simulated and natural vaginal matrices, as well as the "multi-site prospective clinical study" mentioned for validation of cut-offs, represent data used to establish and confirm the device's operational parameters. However, calling these a "training set" in the context of advanced AI algorithms (like those in machine learning) might be a misinterpretation given the nature of a PCR-based diagnostic with defined analytical cut-offs. The largest dataset mentioned for performance evaluation is the prospective clinical study (1763 enrolled subjects).

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

As noted above, a distinct "training set" for an AI model (in the sense of supervised learning) is not explicitly described. However, if we interpret "training set" broadly as the data used to initially establish and refine the device's operational parameters and cut-offs, the ground truth was derived from the following:

• Pre-clinical studies: Utilized targeted organisms (or plasmid DNA) spiked into simulated vaginal matrix at varying, known concentrations (e.g., for LoD determination, precision studies). The "expected result" in these analytical studies served as the ground truth.
• Prospective clinical study data: Data from the 1763 enrolled subjects (used to "validate these cut-offs" and performing ROC analysis) employed the composite reference standards described in section 7 (Nugent/Amsel for BV, Culture/Sequencing for Candida, Wet Mount/Culture for T. vaginalis). These reference methods collectively established the ground truth for clinical specimens against which the device's performance, including its cut-offs, was evaluated and confirmed.

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The BD MAX™ MRSA XT assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ MRSA XT assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose MRSA infections nor guide or monitor treatment for MRSA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The BD MAX™ System and the BD MAX™ MRSA XT assay 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 MRSA NEG, MRSA POS or MRSA UNR (Unresolved)] 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.

Here's a breakdown of the requested information based on the provided text:

Acceptance Criteria and Device Performance Study for BD MAX™ MRSA XT Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for all performance analytical and clinical metrics. However, it presents the results of various studies which implicitly define the performance achieved. For the purpose of this response, I've inferred "acceptance criteria" from the satisfactory performance reported by the manufacturer. The clinical performance is compared against a "Reference Method" (Direct/Enriched Culture).

• Moderate Positive (MP): 100% agreement
• Low Positive (LP): 97.9% agreement
• High Negative (HN): 60.4% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Reproducibility (Site-to-Site) | High agreement for positive/negative samples, reasonable for low positives. | - MP: 100% agreement
• TN: 100% agreement
• LP: 96.7% agreement
• HN: 63.3% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Reproducibility (Lot-to-Lot) | High agreement for positive/negative samples, reasonable for low positives. | - MP: 100% agreement
• TN: 100% agreement
• LP: 96.7% agreement
• HN: 61.1% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Analytical Sensitivity (LoD) | Detection of MRSA strains at low concentrations. | LoD ranged from 64 to 343 CFU/swab at 95% positivity for various MRSA genotypes. |
  | Analytical Inclusivity | Detection of a wide range of MRSA strains and types. | All 77 MRSA strains (across various MREJ genotypes, SCCmec types, PFGE types, geographic origins, and including VRSA/VISA) were detected at 2-3x LoD. |
  | Analytical Specificity | No detection of non-target organisms (MSSA, CoNS, CoPS, other species, viruses). | - Empty cassette variant MSSA: 15/15 MRSA NEG
• Non-staphylococcal species (57 strains): 57/57 MRSA NEG
• Coagulase-Negative/Positive staphylococcal strains (45 strains): 45/45 MRSA NEG
• MSSA (50 strains): 50/50 MRSA NEG
• Viruses (17 species): 17/17 MRSA NEG |
  | Interfering Substances | No interference from common nasal substances/microorganisms. | No reportable interference from 28/29 tested substances/microorganisms. Tobramycin showed reportable interference at 4.5 x 10^-3 g/swab. |
  | Carryover/Cross-Contamination | Low rate of false positives due to carryover. | 3 false positive results out of 210 expected negative results (1.4%). |
  | Clinical Sensitivity (vs. Reference Method) | High agreement for positive specimens. | 93.1% (95% CI: 88.1%, 96.1%) |
  | Clinical Specificity (vs. Reference Method) | High agreement for negative specimens. | 97.5% (95% CI: 96.8%, 98.1%) |
  | Positive Predictive Value (PPV) (vs. Reference Method) | Reasonable PPV given prevalence. | 73.2% (95% CI: 67.8%, 78.3%) |
  | Negative Predictive Value (NPV) (vs. Reference Method) | High NPV. | 99.5% (95% CI: 99.1%, 99.7%) |
  | Positive Percent Agreement (vs. Direct Culture) | High agreement for positive specimens. | 96.5% (95% CI: 92.0%, 98.5%) |
  | Negative Percent Agreement (vs. Direct Culture) | High agreement for negative specimens. | 96.9% (95% CI: 96.1%, 97.6%) |
  | Unresolved Rate (Initial) | Low initial unresolved rate. | 0.6% (16/2399) |
  | Unresolved Rate (After Repeat) | Very low unresolved rate after repeat. | 0.1% (2/2398) |

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

• Clinical Performance Study:

  • Test Set Size:
    • Reference Method comparison: 2352 compliant specimen results used for sensitivity/specificity calculations. A total of 2451 specimens were initially enrolled, with 94 noncompliant and 5 non-reportable PCR results removed.
    • Direct Culture comparison: 2391 compliant specimen results used for positive/negative percent agreement. A total of 2451 specimens were initially enrolled, with 54 noncompliant and 6 non-reportable PCR results removed.
  • Data Provenance: Multi-site prospective investigational study. Specimens were collected from patients at risk for nasal colonization from three investigational centers (countries not explicitly stated but typically within the regulatory region, e.g., North America for an FDA submission).

• Analytical Studies (e.g., Sensitivity, Specificity, Inclusivity, Precision, Reproducibility): These studies used prepared samples (simulated nasal matrix, bacterial suspensions) and well-characterized strains from public collections and clinical isolates. The Analytical Inclusivity study explicitly states that 77 MRSA strains were from 27 countries.

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

• The ground truth for the clinical performance study test set was established using a Comparative Reference Method consisting of direct culture complemented by enriched culture.
• The document does not explicitly state the number of experts or their specific qualifications (e.g., microbiologists, lab technologists) involved in performing or interpreting these culture methods at the clinical sites. However, it details the laboratory procedures: presumptive S. aureus colonies on selective media, subculture to Blood Agar, identification confirmation with an agglutination test, and methicillin-resistance confirmation by Cefoxitin disk diffusion susceptibility testing. For enriched culture, TSB 6.5% NaCl broth was used, followed by inoculation of chromogenic medium and BA plates, with MRSA confirmation as described. This implies trained laboratory personnel using standardized microbiological techniques.

4. Adjudication Method for the Test Set

• The document describes a "Reference Method" (Direct/Enriched Culture) as the independent ground truth standard.
• For discordant results between the BD MAX™ MRSA XT assay and the Reference Method in the clinical study, further investigation was performed.
  • "12 of 54 MRSA False Positive BD MAX™ MRSA XT specimens were found to be MRSA POS after repeat of Reference Method."
  • "5 of 11 MRSA False Negative BD MAX™ MRSA XT specimens were found to be MRSA NEG after repeat of Reference Method."
  • This indicates a form of adjudication by repeat testing using the Reference Method (culture) for discordant clinical samples. It is not a 2+1 or 3+1 expert consensus model, but rather re-evaluation using the established gold standard.

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/interpreters with and without AI assistance was not done.
• This device is an automated in vitro diagnostic test (NAAT) for direct detection of MRSA DNA. Its results are automatically interpreted by the BD MAX™ System software (MRSA NEG, MRSA POS, MRSA UNR).
• The comparison is between the automated device performance and traditional culture methods, not between human performance with and without AI assistance.

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

• Yes, a standalone performance evaluation was done.
• The entire premise of the analytical and clinical performance studies is to assess the BD MAX™ MRSA XT assay's performance as an automated qualitative in vitro diagnostic test. The device generates "MRSA NEG, MRSA POS or MRSA UNR (Unresolved)" results automatically.
• The "Substantial Equivalence" section explicitly states that the "Interpretation of Test Results" is "Automated (Diagnostic software of BD MAX™ System)."
• The clinical performance section directly compares "BD MAX™ MRSA XT Assay" results to the Reference Method and Direct Culture.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

• Clinical Performance Study: The ground truth for clinical performance was established by a Comparative Reference Method consisting of direct culture complemented by enriched culture. This is a laboratory-based microbiological gold standard.
• Analytical Performance Studies (e.g., LoD, Inclusivity, Specificity): The ground truth was established by known concentrations of characterized bacterial strains (e.g., CFU/swab), often from controlled laboratory settings or public reference collections.

8. The Sample Size for the Training Set

• The document does not provide details about a specific training set size for the BD MAX™ MRSA XT assay's algorithm.
• This is a molecular diagnostic test (PCR), and its performance is determined by the design and optimization of the primers and probes, and the reaction conditions, rather than a machine learning model that requires a "training set" in the conventional sense of AI. The analytical validation experiments (LoD, inclusivity, specificity) are used to characterize the assay's performance across a wide range of relevant targets and non-targets, ensuring its robustness and accuracy.

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

• As noted above, the concept of a "training set" in the context of a machine learning algorithm is not directly applicable here.
• The development and optimization of the PCR assay would involve:
  • Designing primers and probes to target specific MRSA DNA sequences (e.g., MREJ, mecA, mecC).
  • Testing against characterized bacterial strains with known genotypes, SCCmec types, and concentrations to ensure accurate detection and specificity.
  • Optimizing reaction parameters (e.g., temperatures, times, reagent concentrations).
• The ground truth for these developmental and optimization activities would be derived from established molecular biology techniques, bacterial genotyping, sequencing, and quantitative culturing methods to confirm the presence, identity, and concentration of target DNA.

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The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes realtime polymerase chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The BD MAX™ System and the BD MAX™ StaphSR assay 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 [SA NEG MRSA NEG (negative)], [SA POS, MRSA POS (MRSA positive)], [SA POS, MRSA NEG (SA positive)] or [SA UNR, MRSA UNR (Unresolved)] 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 BD MAX™ StaphSR assay is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs. The performance of the device was evaluated in both analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the BD MAX™ StaphSR assay are primarily based on achieving certain levels of sensitivity and specificity when compared against a reference method (direct culture complemented by enriched culture). The document details the reported performance for MRSA and SA detection.

Acceptance Criteria and Reported Performance for BD MAX™ StaphSR Assay

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

For the clinical performance studies, a total of 2451 specimens were enrolled. After excluding non-compliant specimens, 2354 specimen results were used to determine the clinical performance against the Reference Method, and 2393 specimen results were used for comparison against Direct Culture.

The data provenance for the clinical study is prospective, collected from three geographically diverse investigational centers. The specific countries of origin for these centers are not explicitly stated.

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

The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with X years of experience). However, the ground truth was established using laboratory methods rather than expert interpretation of images or clinical assessments.

4. Adjudication Method for the Test Set

The adjudication method for the clinical test set involved a Comparative Reference Method consisting of direct culture complemented by enriched culture.

• For specimens negative for MRSA or SA by direct culture, enriched culture analysis was performed.
• Presumptive S. aureus colonies on chromogenic medium were subcultured onto Blood Agar (BA) for identification confirmation with an agglutination test.
• Methicillin resistance was confirmed by Cefoxitin disk (30 µg) diffusion susceptibility testing.
• Enrichment in Trypticase Soy Broth with 6.5% NaCl was carried out if MRSA or SA was not confirmed by initial direct culture.
• Turbid TSB 6.5% NaCl broth was used to inoculate additional chromogenic medium and BA plates, and MRSA confirmation followed the same procedure.
• Further investigation was performed on specimens with discordant results between the Reference Method and the BD MAX™ StaphSR assay. For MRSA, 12 of 54 false positive and 5 of 11 false negative BD MAX™ StaphSR specimens were re-evaluated by the Reference Method. For SA, 28 of 118 false positive and 23 of 52 false negative BD MAX™ StaphSR specimens were re-evaluated by the Reference Method.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, What was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

This information is not applicable as the BD MAX™ StaphSR assay is an automated in vitro diagnostic test (molecular assay) for direct detection of DNA. It does not involve "human readers" or AI assistance in the interpretation of results in the context of an MRMC study. The device provides an automated interpretation of results.

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

Yes, a standalone performance study was done. The BD MAX™ StaphSR assay is an automated instrument-based test that directly provides a qualitative result ([SA NEG MRSA NEG], [SA POS, MRSA POS], [SA POS, MRSA NEG], or [SA UNR, MRSA UNR]). The clinical performance data presented in Tables 10-17 directly reflect the standalone performance of the assay compared to the reference microbiological methods.

7. The Type of Ground Truth Used

The ground truth used for both the analytical and clinical studies was based on microbiological culture methods:

• Direct culture complemented by enriched culture for clinical performance evaluation.
• Cultured bacterial suspensions and well-characterized clinical isolates for analytical studies (e.g., LoD, inclusivity, specificity, competitive inhibitory effect).

8. The Sample Size for the Training Set

The document describes premarket studies for a diagnostic device. For such devices, there isn't typically a "training set" in the machine learning sense. Instead, development and optimization are performed using various analytical samples and potentially some initial clinical samples, followed by a robust validation (clinical performance) on an independent set. The details of any specific samples used for internal development or optimization (analogous to a training set) are not provided in this 510(k) summary. The provided sample sizes relate to the analytical validation and the final clinical validation dataset.

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

Given that this is a molecular diagnostic assay and not an AI/ML-based image interpretation product, the concept of a "training set" with ground truth established in that context is not directly applicable. If one were to consider the samples used for assay development and optimization as a "training set," their ground truth would have been established through known bacterial cultures (characterized strains, quantified suspensions) and potentially well-characterized clinical isolates with confirmed microbiological status (e.g., through traditional culture, biochemical tests, and susceptibility testing). However, specific details of such "pre-validation" ground truth establishment are not provided in this regulatory summary.

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The BD MAX™ Cdiff Assay performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct, qualitative detection of the Clostridium difficile toxin B gene (tcdB) in human liquid or soft stool specimens from patients suspected of having C. difficile infection (CDI). The test. performed directly on the specimen, utilizes real-time polymerase chain reaction (PCR) for the amplification of C. difficile toxin B gene DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX ™ Cdiff Assay is intended to aid in the diagnosis of CDI.

The BD MAX™ System and the BD MAX™ Cdiff Assay 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 Ivsis. 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 NEG (negative), POS (positive) or UNR (unresolved) 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.

BD MAX™ Cdiff Assay - Acceptance Criteria and Study Findings

The BD MAX™ Cdiff Assay is an automated in vitro diagnostic test for the direct, qualitative detection of the Clostridium difficile toxin B gene (tcdB) in human liquid or soft stool specimens. The assay is intended to aid in the diagnosis of C. difficile infection (CDI).

1. Table of Acceptance Criteria and Reported Device Performance

The provided document details various analytical and clinical performance studies, but explicit "acceptance criteria" for minimum performance thresholds (e.g., "Sensitivity must be >= 90%") are not stated in a direct, consolidated table. However, the reported performance metrics can be inferred as meeting the implicit acceptance criteria for the submission to be cleared.

Here's a summary of the reported device performance from the provided text, focusing on key metrics:

2. Sample Size and Data Provenance

• Test Set (Clinical Performance Studies):

  • Clinical Performance (vs. Reference Method): 1819 compliant and reportable results from 2071 initial soft or liquid stool specimens.
  • Clinical Performance (vs. Direct Culture): 1826 compliant and reportable results.
  • Comparison Studies: 2013 specimens tested across two external sites (specific breakdown per comparator assay: 647 for one and 1366 for the other).
  • Data Provenance: Multi-site prospective investigational study from six investigational centers. The document does not specify countries of origin, but the submitting company is Canadian. The study was prospective, as specimens were from "patients suspected of having C. difficile infection for which diagnostic tests were indicated and ordered."

• Training Set: The document does not provide specific details on a separate "training set" for algorithm development. This is common for molecular diagnostic assays where the "training" (e.g., selection of primers/probes, optimization of PCR conditions) is inherent in the assay's design and analytical validation, rather than a distinct machine learning training phase.

3. Number of Experts and Qualifications for Ground Truth

• Ground Truth for Clinical Performance (Reference Method): The ground truth was established by a "Comparative Reference Method consisting of direct culture complemented by enriched culture." The anaerobic culture was used to isolate C. difficile, followed by confirmation of isolate identification and a "Tissue Culture Cytotoxicity Assay to determine the toxigenicity of the isolate." This process typically involves trained microbiology laboratory personnel, but the specific number and qualifications of "experts" (e.g., clinical microbiologists, laboratory directors) involved in establishing the final ground truth from this multi-step process are not explicitly stated in the document.

• Ground Truth for Analytical Studies (e.g., LoD, Inclusivity, Specificity): For analytical studies, ground truth was based on known concentrations of bacterial strains (CFU/mL or genomic copies/mL) or known presence/absence of certain organisms, established through standard laboratory methods of quantification and identification. No "experts" in the sense of clinical reviewers are typically involved in establishing these analytical truths.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (e.g., 2+1, 3+1 reviewer consensus) by human experts for the clinical test set results. The ground truth for the clinical performance was established by a "Comparative Reference Method" (direct culture + enriched culture + toxigenicity testing). Discordant results between the BD MAX™ Cdiff Assay and this Reference Method were further investigated:

• "27 of 48 False Positive BD MAX™ Cdiff specimens were also found to be positive using another commercially available FDA-cleared RT-PCR assay targeting the C. difficile tcdB gene."
• "32 of 37 False Negative BD MAX™ Cdiff specimens, were also found to be negative using another commercially available FDA-cleared RT-PCR assay targeting the C. difficile tcdB gene."
  This "further investigation" serves as a form of resolution for discordant cases but is not a traditional multi-reader "adjudication" process using human interpretation of images or clinical data.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was described. The device is an automated in vitro diagnostic test that provides a qualitative (positive/negative) result, meaning there is no human "reader" in the loop for interpreting the assay's output that would then be compared to human performance with or without AI assistance. The study compares the device's performance against a reference method and other FDA-cleared molecular assays.

6. Standalone Performance

Yes, a standalone (algorithm only without human-in-the-loop performance) study was done. The entire clinical and analytical performance evaluation describes the performance of the BD MAX™ Cdiff Assay as a standalone device. The assay automates sample preparation, nucleic acid amplification, and detection, with the BD MAX™ System software automatically interpreting test results as NEG (negative), POS (positive), or UNR (unresolved).

7. Type of Ground Truth Used

• Clinical Performance Studies: The ground truth was based on a "Comparative Reference Method" which primarily relied on culture-based methods (direct and enriched anaerobic culture to isolate C. difficile) combined with a Tissue Culture Cytotoxicity Assay to determine the toxigenicity of the isolated strains. This represents a combination of microbiological culture and a functional assay (outcome of bacterial toxin activity on cells).
• Analytical Performance Studies (LoD, Inclusivity, Specificity): The ground truth was based on known characterized bacterial strains and their concentrations, determined by standard microbiological quantification methods.

8. Sample Size for the Training Set

The document does not specify a distinct "training set" sample size in the context of the device's development or a machine learning algorithm. For molecular diagnostic assays like this, the "training" involves the scientific development and optimization of the assay components (primers, probes, reaction conditions) performed by molecular biologists and R&D scientists, rather than a separate data-driven training phase for an AI model.

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

As described above, no explicit "training set" with established ground truth in the machine learning sense is detailed. The assay's design and optimization (analogous to "training" in AI development) would have utilized known positive and negative controls, characterized bacterial strains, and various concentrations to perfect the real-time PCR parameters and ensure accurate detection of the tcdB gene. This process involves standard laboratory validation techniques rather than human expert annotation for ground truth.

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The BD MAX™ MRSA Assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of Methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ MRSA Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose, guide or monitor MRSA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The BD MAX™ MRSA Assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of Methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The assay also includes a Sample Processing Control (SPC). The Sample Processing Control is present in the Extraction Tube and undergoes the extraction and amplification steps to monitor for inhibitory substances as well as process inefficiency due to instrument or reagent failure. No operator intervention is necessary once the clinical sample and reagent strip are loaded into the BD MAX™ System. The BD MAX™ System automates sample lysis, DNA extraction and concentration, reagent rehydration, nucleic acid amplification and detection of the target nucleic acid sequence using real-time polymerase chain reaction (PCR). Amplified targets are detected with hydrolysis probes labeled with quenched fluorophores. The amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System.

The BD MAX™ System uses a combination of lytic and extraction reagents to perform cell lysis and DNA extraction. Following enzymatic cell lysis at elevated temperature, the released nucleic acids are captured by magnetic affinity beads. The beads with the bound nucleic acids are washed and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized with Neutralization Buffer and transferred to the Master Mix Tube to rehydrate PCR reagents. The reconstituted amplification reagent is dispensed into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to prevent evaporation and amplicon contamination.

The amplified DNA targets are detected using hydrolysis (TagMan®) probes labeled at one end with a fluorescent reporter dye (fluorophore) and at the other end with a quencher moiety. Probes labeled with different fluorophores are used to detect MRSA and SPC amplicons in two different optical channels of the BD MAX™ System: MRSA amplicons are detected in the FAM channel and SPC amplicons are detected in the ROX channel. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the two optical channels used for the BD MAX™ MRSA Assay is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System measures these signals at the end of each amplification cycle, and interprets the data to provide a result.

1. Acceptance Criteria and Device Performance:

The acceptance criteria are not explicitly stated as numerical thresholds in the provided document. However, the study aims to demonstrate substantial equivalence to the predicate device (BD GeneOhm™ MRSA ACP Assay) based on the presented sensitivity and specificity values. Therefore, the device's performance metrics serve as the "reported device performance" against an implied standard of clinical utility and equivalence.

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

• Sample Size:
  • Clinical Performance (Reference Method): 1903 specimens were reference method compliant (Table 2, footnote 3).
  • Comparison to Direct Culture: 1881 specimens (Table 3).
  • Unresolved Rates: 1884 specimens were PCR method compliant for initial rates, and 1882 for rates after repeat (Table 5, footnote 2).
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the submission is from GeneOhm Sciences Canada Inc. (BD Diagnostics) and the FDA approval is from the US. The study involved "multi-site prospective investigational study" with "Four (4) investigational centers participated," suggesting US or North American data.
  • Retrospective or Prospective: Prospective. The document states: "Clinical performance characteristics of the BD MAX™ MRSA Assay were determined in a multi-site prospective investigational study."

3. Number of Experts and Qualifications for Ground Truth:

The document does not mention the use of human experts to establish the ground truth in the traditional sense of consensus reading for diagnostic imaging or clinical assessment.

• Ground Truth Method: The "Comparative Reference Method" used a laboratory-based process: direct culture complemented by enriched culture. The identification of S. aureus was confirmed with an agglutination test, and Methicillin-resistance was confirmed by Cefoxitin disk diffusion susceptibility testing. No human experts are described as providing subjective interpretations for ground truth.

4. Adjudication Method for the Test Set:

Not applicable. The ground truth was established through objective laboratory culture and susceptibility testing, not through expert consensus or a process that would require adjudication.

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

• No, an MRMC comparative effectiveness study was not done. This device is an automated, in vitro diagnostic molecular assay (PCR-based), not an imaging or clinical interpretation tool that relies on human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply in this context.

6. Standalone Performance Study:

• Yes, a standalone study was performed. The entire clinical performance section (Tables 1-5) details the performance of the BD MAX™ MRSA Assay (the algorithm/device only) compared to a defined reference method. This is a direct measure of the algorithm's performance without human intervention in result interpretation. The "amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System."

7. Type of Ground Truth Used:

• Laboratory Reference Method: The ground truth was established using a "Comparative Reference Method" which consisted of direct culture complemented by enriched culture. This involved:
  • Presumptive S. aureus colonies on selective media.
  • Subculture onto Blood Agar (BA).
  • Identification confirmed with an agglutination test.
  • Methicillin-resistance confirmed by Cefoxitin disk (30μg) diffusion susceptibility testing.
  • Enrichment in Trypticase Soy Broth with 6.5% NaCl (TSB 6.5% NaCl) for initial direct culture-negative specimens, followed by re-inoculation and MRSA confirmation as above.

8. Sample Size for the Training Set:

• The document does not provide information on the sample size used for the training set. This submission focuses on the performance of the final device in a clinical validation study rather than the development process.

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

• The document does not provide information on how the ground truth for the training set was established. As mentioned above, the focus is on the validation study, not the development data.

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The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. The BD GeneOhm™ StaphSR Assay is not intended to monitor treatment for MRSA/SA infections. Subculturing of positive blood cultures is necessary for further susceptibility testing.

The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. To test a positive blood culture, an aliquot of the culture media is transferred into a sample buffer tube and lysed. Following specimen lysis, amplification of the targets (MRSA: a S. aureus specific target and a sequence near the insertion site of the Staphylococcal Cassette Chromosome mec (SCCmec); SA: another S. aureus specific sequence] occurs in the presence of either or both targets. Amplification of the IC, a DNA fragment of 335-bp including a 277-bp sequence not found in S. aureus or MRSA, also takes place unless PCR inhibitory substances are present. The amplified DNA targets are detected with molecular beacon probes, hairpin-forming single-stranded oligonucleotides labelled at one end with a quencher and at the other end with a fluorescent reporter dye (fluorophore). In the absence of target, the fluorescence is quenched. In the presence of target, the hairpin structure opens upon beacon/target hybridization, resulting in emission of fluorescence. For the detection of MRSA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the non-fluorescent quencher moiety DABCYL at the opposite end of the oligonucleotide. For the detection of S. aureus amplicon, the molecular beacon probe is labelled with the fluorophore TexasRed at the 5' end and the quencher DABCYL at the 3' end. For the detection of the IC amplicon, the molecular beacon probe contains the fluorophore TET at the 5' end and the quencher DABCYL at the 3' end, Each beacon-target hybrid fluoresces at a wavelength characteristic of the fluorophore used in the particular molecular beacon probe. The amount of fluorescence at any given cycle, or following cycling, depends on the amount of specific amplicon present at that time. The SmartCycler software simultaneously monitors the fluorescence emitted by each beacon probe, interprets all data, and provides a final result at the end of the cycling program.

Acceptance Criteria and Device Performance for BD GeneOhm™ StaphSR Assay

This document describes the acceptance criteria and study proving the BD GeneOhm™ StaphSR Assay meets these criteria, as presented in the 510(k) Summary K071026.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the BD GeneOhm™ StaphSR Assay are implicitly established through the comparison to predicate devices, where the assay is deemed "substantially equivalent in performance." While specific numerical performance targets are not explicitly stated as "acceptance criteria" in the provided text, the clinical trial results demonstrate the performance achieved. Based on the analysis of the provided tables, the reported device performance for both MRSA and S. aureus detection consistently achieves high levels of positive and negative agreement with reference methods across multiple sites.

Note: The "acceptance criteria" are implied by the claim of "substantial equivalence in performance" to established predicate devices (Remel Staphaurex Latex Agglutination Test, BBL (BD) Oxacillin Screen Agar, and BD Phoenix Automated ID/AST System). The reported device performance demonstrates a high degree of concordance with these reference methods.

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

The clinical trials were performed at five sites. The total sample sizes for the test set across all sites are calculated from the provided tables:

• For MRSA:
  • Site 1: 446 samples
  • Site 2: 133 samples
  • Site 3: 232 samples
  • Site 4: 286 samples
  • Site 5: 86 samples
  • Total MRSA Test Set: 1183 samples
• For S. aureus:
  • Site 1: 446 samples
  • Site 2: 133 samples
  • Site 3: 232 samples
  • Site 4: 286 samples
  • Site 5: 86 samples
  • Total S. aureus Test Set: 1183 samples
    (The sample sizes for MRSA and S. aureus appear to be derived from the same set of positive blood cultures.)

Data Provenance: The document states that the "Clinical trials were performed at five sites." While specific countries of origin for these sites are not explicitly mentioned, it is highly probable that the data were collected in the United States or Canada, given the submitter and contact information (BD Diagnostics, GeneOhm Sciences Canada Inc., with a US Agent in San Diego, CA). The study is prospective in nature, as it is a "clinical trial" evaluating the performance of a new diagnostic assay.

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

The ground truth was established by "reference methods" in clinical laboratories. These reference methods are listed as:

• Remel Staphaurex Latex Agglutination Test (for S. aureus)
• BBL (BD) Oxacillin Screen Agar (for MRSA)
• BD Phoenix Automated ID/AST System (for both S. aureus and MRSA)
• Culture/PBP2' Latex (for MRSA at Site 5)

The document does not specify the number of individual experts (e.g., microbiologists, lab technologists) who interpreted these reference methods at each site, nor their specific qualifications (e.g., years of experience). However, it is implied that these interpretations were performed by qualified laboratory personnel following standard laboratory protocols for these established diagnostic tests.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for discrepancies between the test device and the reference methods. The tables present a direct comparison of the BD GeneOhm™ StaphSR results against the respective reference method results at each site. Any disagreements would have been considered false positives or false negatives against the established reference standard.

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. This study evaluates the performance of a diagnostic assay (BD GeneOhm™ StaphSR) against established laboratory reference methods, not the performance of human readers with or without AI assistance. Therefore, there is no effect size reported for human reader improvement with AI vs. without AI assistance.

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

Yes, this was a standalone study in the context of a diagnostic test kit. The BD GeneOhm™ StaphSR Assay is a PCR-based molecular diagnostic test. The "performance" tables directly compare the output of the "BD GeneOhm™ StaphSR" assay (which includes the entire PCR and detection process interpreted by the SmartCycler software) against the reference culture/ID-AST systems. While human technicians perform the sample preparation and run the assay, the "result" generated by the device itself is interpreted by the SmartCycler software providing a final result at the end of the cycling program. This means the reported performance is the "algorithm only" or "device only" performance in its intended use.

7. The Type of Ground Truth Used

The ground truth used was established by standard microbiological culture and identification/antimicrobial susceptibility testing (ID/AST) methods, which are considered the gold standard for identifying bacterial species and their resistance patterns in clinical microbiology. Specifically, these included:

• Culture/ID-AST System 1, 2, 3
• Culture/Oxacillin Screen Agar
• Culture/PBP2' Latex

These are laboratory reference standards, often supported by expert interpretation of growth characteristics and biochemical or molecular profiles.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This is common for diagnostic assays of this type, where the "training" (development and optimization) often involves laboratory strains and characterized clinical isolates during the assay design phase, rather than a distinct, formally reported "training set" of patient samples in the same manner as machine learning models might have. The clinical trials described here represent the validation or test set.

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

As no specific training set is detailed, the method for establishing its ground truth is also not provided. However, during the development of such assays, ground truth for optimization and development samples would typically be established using well-characterized clinical isolates and reference strains confirmed by extensive phenotypic and genotypic methods, including sequencing, to ensure accurate target and non-target differentiation.

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The IDI-VanR® Assay is a qualitative in vitro test for the rapid detection of vancomycinresistance (vanA and vanB) genes directly from rectal swabs. The IDI-vanR® Assay detects the presence of the vanA and vanB genes that can be associated with vancomycin-resistant enterococci (VRE). The assay is performed on an automated realtime PCR instrument with rectal swabs from patients at risk for VRE colonization. The IDI-VanR® Assay can be used as an aid to identify, prevent and control vancomycinresistant colonization in healthcare settings. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification. The IDI-VanR® Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections.

Following specimen lysis, amplification of the vanA and vanB targets occurs. Amplification of the IC, a DNA fragment of 294-bp including a 254-bp sequence not found in VRE, will also take place unless there are PCR inhibitory substances. The amplified DNA targets are detected with molecular beacons, a hairpin-forming single-stranded oligonucleotides labelled at one end with a quencher and at the other end with a fluorescent reporter dye (fluorophore). In the absence of target, the fluorescence is quenched. In the presence of target, the hairpin structure opens upon beacon/target hybridization, resulting in emission of fluorescence. For the detection of vanA amplicons, the molecular beacon contains the fluorophore FAM at the 5' end and the non-fluorescent quencher moiety DABCYL at the opposite end of the oligonucleotide. For the detection of the vanB amplicons, the molecular beacon contains the fluorophore Texas Red at the 5' end and the quencher DABCYL at the 3' end. For the detection of the Internal Control (IC) amplicons, the molecular beacon contains the fluorophore TET at the 5' end and the quencher DABCYL at the 3' end. Each beacon-target hybrid fluoresces at a wavelength characteristic of the fluorophore used in the particular molecular beacon. The amount of fluorescence at any given cycle, or following cycling, depends on the amount of specific amplicons present at that time. The SmartCycler® software simultaneously monitors the fluorescence emitted by each beacon, interprets all data, and provides a final result at the end of the cycling program.

The GeneOhm Sciences Canada, Inc. IDI-VanR™ Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from rectal swabs, used as an aid to identify, prevent and control vancomycinresistant colonization in healthcare settings.

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

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds that the device must meet. Instead, it presents the device's performance in comparison to a predicate device and culture technique, implying that substantial equivalence to the predicate (Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV)) serves as the primary "acceptance criterion" for market clearance.

However, based on the presented clinical performance data, we can infer the reported performance of the IDI-VanR™ Assay.

• Overall Sensitivity: 97.3% (95% CI: 92.2%-99.4%)
• Overall Specificity: 91.4% (95% CI: 89.3%-93.2%)
• Negative Predictive Value (NPV): 99.6% (95% CI: 98.9%-99.9%)
• Positive Predictive Value (PPV): 59.1% (95% CI: 51.6%-66.4%)

Detailed breakdown by gene (Table 1):

• Sensitivity VanA': 97.1% (95% CI: 91.6-99.4%) (Note: VanA' includes vanA alone and vanA+B PCR results considered true positive where culture was vanA positive.)
• Sensitivity VanB: 57.1% (95% CI: 1.8-90.1%) (Acknowledged as low due to low number of vanB positive specimens).
• Specificity (combined for vanA, vanB, vanA+B, negative): 91.4% (This specificity seems to be derived from the overall calculation in Table 2, not solely from Table 1's detailed breakdown, as a direct calculation from Table 1's "Negative" row would be different if only negative cultures were considered.)

Unresolved Rate:

• Initial: 0.2% (2/968)
• After repeat testing: 0.1% (1/968) |

Note on "Acceptance Criteria": In 510(k) submissions, the primary "acceptance criterion" is often substantial equivalence to a predicate device. The performance metrics presented are to demonstrate that the new device is as safe and effective as the predicate. While specific numerical targets might not be explicitly stated as "acceptance criteria," regulatory bodies assess if the presented performance is acceptable for the intended use and comparable to established methods.

Study Details:

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

   • Total Sample Size: 968 rectal swab specimens.
   • Data Provenance: Clinical trials were performed at four investigational sites. The country of origin is not explicitly stated for all sites, but the submitter is GeneOhm Sciences Canada, Inc., suggesting at least some Canadian sites. The study appears to be prospective as it evaluates the performance of the IDI-VanR™ Assay against culture technique in a clinical trial setting.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth (comparator method) was the "Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) with phenotypic identification of presumptive Enterococcus colonies and determination of vancomycin and teicoplanin resistance (CLSI, M7-A6 and M100-S15)." This implies that laboratory personnel trained in microbiology and following established clinical guidelines (MMWR, CDC, CLSI) performed the ground truth testing.

3. Adjudication method for the test set:

   • The document does not describe a formal adjudication method (e.g., 2+1, 3+1). The ground truth was established by the predicate culture method, and the device's results were compared against this. Any discrepancies would typically be resolved by retesting or further investigation according to the study protocol, though this specific detail is not provided.

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 is not an AI/CAD device. The IDI-VanR™ Assay is a nucleic acid amplification test (real-time PCR) for detecting specific genes. Therefore, an MRMC study with human readers and AI assistance is not applicable to this device.

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

   • Yes, the performance presented is for the device operating stand-alone. The IDI-VanR™ Assay is an in vitro diagnostic test, and its results (positive/negative for vanA/vanB) are generated by an automated real-time PCR instrument and software. The reported sensitivity and specificity refer to the device's performance as a primary diagnostic tool against the reference method.

6. The type of ground truth used:

   • The ground truth used was culture technique (Remel Bile Esculin Azide agar with vancomycin) combined with phenotypic identification of Enterococcus colonies and determination of vancomycin and teicoplanin resistance according to established clinical and laboratory standards (MMWR, CDC, CLSI M7-A6 and M100-S15). This is a well-accepted and standard method for identifying VRE.

7. The sample size for the training set:

   • The document does not mention a training set. This is typical for in vitro diagnostic tests like PCR assays. These types of assays are based on established molecular biology principles and validated against known controls and clinical samples without a "training set" in the machine learning sense. The assay's parameters (e.g., primer and probe design, cycling conditions) would be developed and optimized in a lab setting, not through machine learning training on a large dataset.

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

   • As there is no mention of a training set, this question is not applicable. The assay's fundamental design is based on known genetic sequences (vanA and vanB) and molecular detection methods, not on data-driven training. Development would involve extensive analytical validation using characterized bacterial strains and clinical samples to optimize performance characteristics.

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