(224 days)
To determine gram-negative and gram-positive bacterial susceptibility against the antimicrobial agent Trovafloxacin.
Organisms with indications for testing* include:
Gram-Negative Bacteria Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Gram-Positive Bacteria Methicillin susceptible Staphylococcus aureus Methicillin susceptible Staphylococcus epidermidis Enterococcus faecalis Streptococcus agalactiae (Gp.B) Streptococcus pyogenes (Gp.A)
- As taken from the Indications and Usage section of the manufacturer's package insert (Issued: December 1997).
The MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Trovafloxacin are not intended for use with Streptococcus pneumoniae and viridans streptococci.
Microdilution Minimum Inhibitory Concentration (MIC) Panels. MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels. The manufacturing process for both Test panels called for Trovafloxacin dehydrated in Mueller-Hinton broth. During testing each well was inoculated/rehydrated with the organisms suspended in distilled water with Pluronic. Test panels were read visually after 16-20 hours of incubation at 35° C in a non-CO2 incubator.
Here's an analysis of the acceptance criteria and study details based on the provided text:
Acceptance Criteria and Device Performance Study
The device in question is the MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Trovafloxacin, intended to determine antimicrobial agent susceptibility. The study aimed to demonstrate substantial equivalence to NCCLS frozen Trovafloxacin Reference Panels.
1. Table of Acceptance Criteria and Reported Device Performance
The core acceptance criterion is "Essential Agreement" with the predicate device.
| Acceptance Criterion | Reported Device Performance (Gram-Negative) | Reported Device Performance (Gram-Positive) |
|---|---|---|
| Overall Essential Agreement | 99.7% | 98.7% |
Note: The document refers to FDA DRAFT document "Review Criteria for Assessment of Antimicrobial Susceptibility Devices" (dated May 31, 1991) for defining substantial equivalence and acceptability. While the specific numerical threshold for "acceptable performance" is not explicitly stated in the provided text as a percentage, the reported values exceeding 98% are presented as demonstrating "acceptable performance" in comparison to the reference panels.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document does not explicitly state the total number of isolates (sample size) used for the clinical trial. It does refer to "clinical isolates with a broad range of susceptibilities" and states that "The type and number of isolates tested was in compliance with the FDA guidance 'Review Criteria for Assessment of Antimicrobial Susceptibility Devices: Draft May 1991'". This implies that the sample size adhered to FDA recommendations for such devices at the time.
- Data Provenance: The study was a prospective clinical trial. The text mentions "fresh and stock Efficacy isolates and stock Challenge strains" were used for the external evaluations, implying a mix of recently isolated clinical samples and established laboratory strains. The specific country of origin is not mentioned.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not specify the number of experts or their qualifications. The ground truth was established by "Reference panels were made according to NCCLS recommendations found in NCCLS Document M7-A4 (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, fourth edition; Approved Standard. Pennsylvania, NCCLS, 1997), using cation adjusted Mueller-Hinton broth." This process likely involves trained laboratory personnel following standardized protocols, rather than individual expert adjudication in the traditional sense of image analysis.
4. Adjudication Method for the Test Set
The adjudication method involved a specific protocol for resolving discrepancies:
- Initial Data Analysis: Comparing initial Test MIC results with initial Reference MIC results.
- Discrepancy Resolution: Isolates that exhibited a ≥ 2 dilution error (discrepancy) between the Test and the Reference panel were repeated in triplicate.
- Final Data Analysis: Comparing the initial Test results to the repeat Reference results. Discrepancies were considered resolved when the repeat Reference result was in Essential Agreement with the initial Test result.
- Additional Data Analysis: An additional analysis was performed using repeat results from both the Reference and the Test panels.
This method functions as a form of internal adjudication or re-testing protocol, aiming to confirm the stability of the reference measurement when a significant disagreement occurs. It is not a 2+1 or 3+1 expert consensus model as seen in image interpretation.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This device is an automated antimicrobial susceptibility testing panel, not a diagnostic imaging device that involves human readers interpreting results with or without AI assistance. The performance is gauged by direct comparison to a reference standard (NCCLS frozen panels), not by measuring improvements in human reader performance.
6. Standalone Performance Study
Yes, a standalone (algorithm only without human-in-the-loop performance) study was performed. The entire clinical investigation focuses on comparing the output of the MicroScan® Dried panels (the device being evaluated) directly against the NCCLS frozen reference panels. While visual reading is mentioned for both (after 16-20 hours of incubation), the core of the evaluation is the intrinsic performance of the device in generating MIC values compared to the established reference standard, without involving a human interpretation step that requires "assistance." The "visual reading" refers to the method of determining the MIC endpoint from the wells, which is a standard procedure in microbiology, not an interpretation with expert variability.
7. Type of Ground Truth Used
The ground truth used was expert consensus / reference standard based on established laboratory methods. Specifically, the reference panels were "made according to NCCLS recommendations found in NCCLS Document M7-A4 (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, fourth edition; Approved Standard. Pennsylvania, NCCLS, 1997), using cation adjusted Mueller-Hinton broth." The NCCLS (now CLSI) standards represent the gold standard for antimicrobial susceptibility testing.
8. Sample Size for the Training Set
The document does not mention a training set or its sample size. This type of susceptibility testing device typically does not involve a "training set" in the machine learning sense. Instead, the device's design and manufacturing process are developed, and then its performance is validated against established methods using a test set.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a training set, there is no information on how its ground truth was established.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).