(89 days)
Strep B Carrot Broth™ Kit is a selective and differential medium which is intended for the detection of Group B Streptococus (GBS) from anovaginal specimens collected from pregnant women. The medium is used as an aid in the qualitative determination of GBS colonization in pregnant women. The color change reaction from white to orange is representative of a positive result for presence of GBS. The medium requires 24 hours of incubation but positive results can be interpreted and reported as early as 16 hours. Due to the properties of Strep B Carrot Broth™ Kit, non-hemolytic GBS cannot be detected by the medium's color change and require subculture for identification. Any presumptive negative indicated by lack of color change at the end of the incubation period must be subcultured to a non-selective medium (e.g., Tryptic Soy Agar with 5% Sheep Blood) to confirm absence of GBS. Subculture must also be performed to recover isolates for conducting susceptibility testing as recommended for penicillin-allergic women.
Strep B Carrot Broth™ is a selective and differential medium with selective components designed to enrich for Group B Streptococci. The production of a light orange, or red-orange pigment is a unique characteristic of β-hemolytic GBS due to reaction with substrates such as starch, and folate pathway inhibitors. GBS detection by color with Strep B Carrot Broth™ is only possible with β-hemolytic Group B Streptococci colonies, which provides evidence of a direct genetic linkage between pigment production in this media and hemolysin production. Non-hemolytic GBS can be recovered Strep B Carrot Broth™ upon subculture to 5% sheep blood agar plates.
The device in question is the Strep B Carrot Broth™ Kit, a selective and differential medium intended for the detection of Group B Streptococcus (GBS) from anovaginal specimens collected from pregnant women. It aids in the qualitative determination of GBS colonization.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity or specificity thresholds. However, the performance data presented implies a comparison against a reference method (LIM Broth with subculture and biochemical testing). The "Substantially Equivalent?" column in the comparison table (page 4) suggests that similar performance for "Intended Use," "Methodology," "Inoculation," and "Sample Type" were considered for equivalence. For quantitative performance, the comparison against the reference method served as the implicit acceptance benchmark.
Based on the provided performance tables, here's a summary of the device's performance:
| Criterion / Performance Metric | Reported Device Performance (Overall) - Color Reaction Only (Table 1) | Reported Device Performance (Overall) - Color Reaction + Subculture of Negatives (Table 2) |
|---|---|---|
| Sensitivity for GBS detection (color reaction) | 87.73% (95% CI: 81.8 - 91.9) | N/A (This metric is less relevant when incorporating subculture for negatives) |
| Specificity for GBS detection (color reaction) | 98.83% (95% CI: 97.6 - 99.4) | N/A |
| Sensitivity for GBS detection (color reaction + subculture of negatives) | N/A | 98.8% (95% CI: 95.6 - 99.7) |
| Specificity for GBS detection (color reaction + subculture of negatives) | N/A | 97.9% (95% CI: 96.4 - 98.7) |
| Recovery of β-hemolytic GBS (Color reaction only, considering non-hemolytic as negative) | 90.4% (95% CI: 84.7-94.1) * (based on footnote 3, page 5) | N/A |
| Specificity for β-hemolytic GBS (Color reaction only, considering non-hemolytic as negative) | 98.5% (95% CI: 97.2-99.2) * (based on footnote 3, page 5) | N/A |
| Limit of Detection (LoD) | 10^0 CFU/mL (for S. agalactiae ATCC 12386 and ATCC 12403) | N/A |
| Analytical Reactivity (GBS strains) | 54/54 (100%) ATCC and clinical GBS strains produced expected color or recovered upon subculture | N/A |
| Analytical Specificity (Non-target organisms) | 78/78 (100%) non-target organisms produced negative color reaction | N/A |
| Microbial Interference | Target organisms recovered/color produced in presence of high conc. (1.5 x 10^8 CFU/mL) of all but one non-target. E. faecalis required lowering its concentration for recovery/color reaction. | N/A |
| Incubation Time Range | 16-24 hours | N/A |
| Specimen Stability for Transport Media | Varied by transport system; up to 96 hours at 2-8°C for Healthlink, and up to 120 hours at 2-8°C for TransPRO™. | N/A |
| Reproducibility | >95% agreement with known test results | N/A |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Performance Study: 771 valid specimens. An initial 884 specimens were collected, but 113 were excluded.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the study was conducted at "four geographically diverse hospitals with routine GBS specimen." Given the FDA submission from a US company (Hardy Diagnostics, Santa Maria, CA), it is highly probable the data is from the United States.
- Retrospective or Prospective: The study describes evaluating the performance of the Strep B Carrot Broth™ "against routine culture," using "routine GBS specimens." This phrasing, along with the collection of specimens and subsequent testing, suggests a prospective collection and testing of new specimens, though the document does not explicitly state "prospective study."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly specify the number of experts used or their qualifications for establishing the "ground truth" for the clinical test set. The ground truth was established by:
- "routine culture, defined as the selective enrichment of specimen in LIM Broth, followed by subculture to Blood Agar and confirmed by biochemical testing."
- Organisms that grew on Blood Agar were confirmed using "gram-stain, catalase test, and latex agglutination."
- For discrepant analysis, isolates were sent back to Hardy Diagnostics for confirmation, where their identity was confirmed (β GBS, NH GBS, or non-GBS).
This suggests standard microbiology laboratory procedures were followed, implying trained microbiologists or laboratory technicians were involved in establishing the ground truth.
4. Adjudication Method for the Test Set
The data indicates an adjudication process for discrepant isolates.
- "All discrepant isolates were frozen in CryoSavers™ with Brucella Broth and returned to Hardy Diagnostics for testing."
- "The identity of each isolate was confirmed (β Group B Streptococi, NH Group B Streptococi, or non-Group B Streptococi)."
- "Once the identity was confirmed, positive organisms (β Group B Streptococi or NH Group B Streptococi) were tested at LoD (10^0 CFU/mL) in donated negative-vaginal rectal matrix for their recovery from the LIM reference method, color development in Carrot Broth™ Kit, and recovery from the Carrot Broth™ Kit to Blood Agar System."
- Footnotes 1 and 2 on page 5 further detail the re-testing and confirmation process for false positives and false negatives based on the initial comparison.
This represents a form of independent adjudication performed by Hardy Diagnostics on all discrepant samples to determine the true status of the sample.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not conducted. This device is a culture medium, not an AI-assisted diagnostic tool interpreted by human readers. The clinical study compares the performance of the new culture medium (Strep B Carrot Broth™ Kit) against a predicate culture medium (LIM Broth) and standard microbiological confirmatory tests.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device is a standalone diagnostic tool in the sense that its primary output (color change and/or subculture) is directly interpreted. There is no "algorithm only" performance as it's a biochemical reaction in a broth medium. The interpretation of the color change is visual, and subsequent subculture and biochemical testing for negatives are laboratory procedures. Its performance as a standalone culture medium for GBS detection is what was evaluated.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical performance study was established by standard microbiological culture methods and confirmatory tests. Specifically:
- Selective enrichment in LIM Broth.
- Subculture to Blood Agar.
- Confirmation by biochemical testing (gram-stain, catalase test, and latex agglutination).
- For discrepant analysis, full re-testing and confirmation of isolates at Hardy Diagnostics.
This represents a robust, laboratory-based "reference standard" or "gold standard" for GBS detection.
8. The Sample Size for the Training Set
This type of product (a culture medium) does not typically involve a "training set" in the machine learning sense. Its performance is based on its inherent biochemical and selective properties. Therefore, there is no training set for this device.
9. How the Ground Truth for the Training Set Was Established
As there is no training set for a culture medium, this question is not applicable. The "ground truth" principles applied to its development would stem from established scientific principles of bacteriology, media formulation, and GBS characteristics rather than a data-driven training process.
§ 866.2360 Selective culture medium.
(a)
Identification. A selective culture medium is a device that consists primarily of liquid or solid biological materials intended for medical purposes to cultivate and identify certain pathogenic microorganisms. The device contains one or more components that suppress the growth of certain microorganisms while either promoting or not affecting the growth of other microorganisms. The device aids in the diagnosis of disease caused by pathogenic microorganisms and also provides epidemiological information on these diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.