Search Results

The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in the diagnosis of HSV infection in symptomatic patients. The assay is intended to be run on the Abbott m2000 instrument system.

Warning: The IMDx HSV-1/2 for Abbott m2000 assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.

The IMDx FISV-1/2 for Abbott m2000 assay uses PCR to generate amplified product from HSV-1 and HSV-2 present in clinical specimens. The presence of HSV-1 and/or HSV-2 target DNA is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the HSV-1 and/or HSV-2 DNA target concentration present in the original specimen. A plasmid containing DNA unrelated to HSV-1 and HSV-2 is introduced into each specimen during sample preparation to serve as an internal control. The internal control is amplified in the same reaction as the HSV-1 and HSV-2 DNA targets, and serves to demonstrate that the sample preparation and amplification proceeded correctly for each specimen. A preparation of intact, inactivated HSV-1 and HSV-2 virus is included as the positive control in the IMDx HSV-1/2 for Abbott m2000 assay. Run as a separate control, the positive control serves to demonstrate that the HSV-1/2 PCR reagents are functional. In addition, the positive control functions as a process control to demonstrate that sample preparation has proceeded correctly during the run. A negative control consisting of M4RT viral transport medium is included in each run to independently verify the absence of contaminating target material in assay reagents.

Acceptance Criteria and Device Performance Study for IMDx HSV-1/2 for Abbott m2000

The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites.

The study that proves the device meets the acceptance criteria involved Prospective Clinical Performance Characteristics and Retrospective Clinical Performance Characteristics studies, as well as several analytical performance studies. The primary comparison for clinical performance was against the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of target sensitivity and specificity percentages. However, the study results, particularly from the prospective clinical performance, would implicitly represent the performance deemed acceptable for FDA clearance through substantial equivalence. If acceptance criteria were required, they would typically be set at a high level given the diagnostic nature of the device. For this summary, we will present the reported performance from the primary prospective study as the "met acceptance criteria".

Note on HSV-2 Oral Sensitivity: The reported sensitivity of 0.0% in the prospective study for oral HSV-2 is based on only 2 reference method positive cases. This low sample size limits definitive conclusions, and a contrived specimen study was performed to provide additional data for HSV-2 oral detection. This contrived study showed 100% detection of HSV-2 in spiked oral samples across various concentrations.

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

• Prospective Studies (Clinical Performance Characteristics):
  • Test Set Size: 954 prospective specimens (807 anogenital and 147 oral).
  • Data Provenance: From four geographically diverse locations within the United States.
  • Retrospective Studies:
  • Test Set Size: 54 retrospective specimens (27 anogenital and 27 oral).
  • Data Provenance: Not explicitly stated, but "historical results" for the ELVIS system suggests previously collected specimens.

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 the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a commercially available viral culture system, which is a recognized reference method for HSV detection and typing. The document does not specify the number of human experts or their qualifications involved in interpreting the ELVIS results for establishing ground truth. The ELVIS system itself is the "expert" or gold standard in this context.

4. Adjudication Method for the Test Set

The document mentions "Discordant analysis" was performed.

• For anogenital HSV-1, 20 initial IMDx positive / ELVIS negative results were analyzed; 6 were confirmed positive for HSV-1, 11 remained discordant.
• For anogenital HSV-2, 68 initial IMDx positive / ELVIS negative results were analyzed; 55 were confirmed positive for HSV-2, 7 remained discordant.
• For oral HSV-1, 24 initial IMDx positive / ELVIS negative results were analyzed; 14 were confirmed positive for HSV-1, 10 remained discordant.
• For oral HSV-2, 2 initial IMDx positive / ELVIS negative results were analyzed; both were confirmed positive for HSV-2.

The specific "adjudication method" beyond re-testing or further analysis of discordant samples with an unspecified method is not detailed (e.g., whether a third, independent gold standard was used, or if expert review of discrepant results was performed). However, the results presented in the tables incorporate the outcomes of this discordant analysis by adjusting the counts (e.g., "HSV-1 was detected in 6 of the 17 specimens" changes the true positive count for HSV-1).

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 device is an in vitro diagnostic assay (a lab test), not an imaging or interpretation assistance device for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here. The device provides a direct qualitative detection and differentiation of HSV-1/2 DNA.

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

Yes, a standalone performance study was done. The entire set of clinical performance characteristics (prospective and retrospective studies) evaluates the performance of the IMDx HSV-1/2 for Abbott m2000 assay directly against the reference method (ELVIS viral culture). This is an "algorithm only" or "device only" performance without human interpretation being the primary variable. The results are based on the device's output.

7. The Type of Ground Truth Used

The primary ground truth used for clinical performance studies was the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a viral culture-based method, which is a widely accepted laboratory gold standard for direct detection of viable virus.

8. The Sample Size for the Training Set

The document does not explicitly describe a separate "training set" for the IMDx HSV-1/2 for Abbott m2000 assay. This is a PCR-based diagnostic test, not a machine learning model that typically requires a distinct training phase with a large dataset. The assay's design and optimization (e.g., primer and probe selection, reaction conditions) would have occurred during development, likely using various characterized samples, but these are not formally presented as a "training set" in the context of this 510(k) submission. Therefore, the concept of a separate "training set" as understood in machine learning is not directly applicable or reported for this type of IVD.

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

As mentioned above, no explicit "training set" is described for this PCR-based IVD. The ground truth for the analytical and clinical validation of the device relies on established laboratory culture methods (ELVIS system for clinical specimens) and characterized viral strains/isolates for analytical studies (e.g., limit of detection, analytical reactivity, cross-reactivity). These reference methods serve as the "ground truth" to evaluate the accuracy of the IMDx assay.

Ask a specific question about this device

The IMDx C. difficile for Abbott m2000 assay is an in vitro diagnostic assay that uses real-time polymerase chain reaction (PCR) amplification for the qualitative detection of nucleic acids encoding the toxin A gene (tcdA) and toxin B gene (tcdB ) sequences of toxigenic strains of Clostridium difficile in human liquid or soft stool specimens collected from patients suspected of having symptoms of Clostridium difficile infection.

The assay is intended to be performed on the Abbott m2000 System (which comprises the Abbott m2000sp and m2000rt instruments) and is indicated for use as an aid in the diagnosis of Clostridium difficile infection. The test is intended to be used directly on liquid or soft stool specimens (unpreserved stool, or stool preserved in Cary Blair transport medium). Negative results do not preclude toxigenic C. difficile infection and should not be used as the sole basis for treatment or other patient management decisions. The IMDx C. difficile for Abbott m2000 assay is intended for professional use. The device is not intended for point-of-care use.

The IMDx C. difficile for Abbott m2000 assay uses PCR to generate amplified product from the tcdA and tcdB/tcdBv genes in toxigenic C. difficile DNA in clinical specimens. The presence of a toxigenic C. difficile target sequence is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the toxigenic C. difficile DNA target concentration present in the original specimen. A bacterial species unrelated to toxigenic C. difficile is introduced into each specimen during sample preparation to serve as a process control. The process control bacteria are lysed simultaneously with toxigenic C. difficile in the specimen, and amplified in the same reaction as the C. difficile targets using PCR, and serve to demonstrate that the entire assay process has proceeded correctly for each specimen.

Here's a breakdown of the acceptance criteria and the study details for the IMDx C. difficile for Abbott m2000 assay, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The acceptance criteria are not explicitly stated in a defined section. However, based on the "Clinical Performance Characteristics" section, we can infer the acceptance criteria are related to the clinical agreement (Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value) when compared to the Bartels® Cytotoxicity Assay for Clostridium difficile Toxin.

Here's a summary of the reported device performance:

Note: For analytical performance metrics like "Precision/Reproducibility" and "Analytical Sensitivity (LoD)", the tables present the results, but specific numerical acceptance criteria (e.g., minimum % agreement for reproducibility or maximum CFU/mL for LoD) are not explicitly outlined as "acceptance criteria." However, the data presented implies that these results were deemed acceptable to demonstrate adequate analytical performance. For example, for "Precision/Reproducibility", achieving high percentage agreement, especially for positive and low positive samples, suggests successful criteria were met.

Study Details

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

   • Total Test Set Sample Size: 1,565 specimens.
     • 1,186 unpreserved stool specimens
     • 379 Cary Blair preserved stool specimens
   • Data Provenance: The study was conducted at "seven (7) geographically diverse locations within the United States from 2011 to 2013." This indicates prospective data collection for a clinical trial.

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

   • The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth was established by a reference assay.

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

   • The document implies a form of discrepancy analysis rather than adjudication by multiple human readers for initial ground truth establishment. For discrepant results between the IMDx C. difficile for Abbott m2000 assay and the Bartels® Cytotoxicity Assay, "sequencing" was used to resolve some of these discrepancies (e.g., for unpreserved stool: 16 samples were sequenced, 13 resolved as negative, 3 remained discrepant; 53 samples were sequenced, 40 resolved as positive, 9 remained discrepant, 4 indeterminate). This suggests a molecular method was used for further investigation of conflicting results, rather than expert consensus on the initial test.

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:

   • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic assay for molecular detection, not an imaging or interpretive device that would typically involve human readers and AI assistance.

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

   • Yes, a standalone performance study was done. The "Clinical Performance Characteristics" section reports the performance of the IMDx C. difficile for Abbott m2000 assay (the algorithm/device) directly against the reference method. There is no mention of human interpretation influencing the assay's output.

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

   • The primary ground truth was established by comparison to the Bartels® Cytotoxicity Assay for Clostridium difficile Toxin. For discrepant results, sequencing was used for further resolution, serving as a secondary, more definitive ground truth for those specific cases.

7. The sample size for the training set:

   • The document does not explicitly state a sample size for a training set. This is a molecular diagnostic assay, and while it uses PCR amplification, the summary focuses on analytical validation and clinical validation against a reference method, rather than a machine learning model that would typically have distinct training and test sets in the same way. The analytical studies (e.g., LoD, reactivity, cross-reactivity) might be seen as foundational "training" for the assay's design, but not in the sense of a machine learning training set with labeled data.

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

   • As mentioned above, a "training set" in the context of machine learning is not described. For the development and analytical validation of the assay, ground truth would have been established through controlled laboratory experiments using well-characterized C. difficile strains and other microorganisms, as described in the Analytical Reactivity and Cross-Reactivity sections. The document indicates these strains were identified and confirmed (e.g., ATCC strains), which serves as their established "ground truth" for analytical purposes.

Ask a specific question about this device