(71 days)
The Ccpheid Smart GBS Assay performed on the Cepheid SmartCycler Dx System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from vaginal/rcctal swab specimens and Lim broth cultures. The test utilizes real-time polymerase chain reaction (PCR) for a unique gene-specific sequence amplification of Streptococcus agalactiae recovered from clinical samples and fluorogenic target specific hybridization for the detection of the amplified DNA. Results from the Smart GBS Assay are intended for use as a method for rapid detection of GBS colonization in antepartum and intrapartum women.
- The use of the Smart GBS for intrapartum screening should not preclude the use of . other strategies (e.g., antepartum testing). Intrapartum Smart GBS results are useful to identify candidates for intrapartum antibiotic prophylaxis when administration of intravenous antibiotics is not delayed pending results.
- The Smart GBS assay does not provide susceptibility results. Culture isolates are . needed for performing susceptibility testing as recommended for penicillin-allergic women.
The Cepheid Smart GBS Assay is a rapid, DNA test for detecting GBS DNA from vaginal/rectal swab specimens from pregnant women. The assay is performed on the automated Cephcid SmartCycler Dx System. The SmartCycler Dx System is a rapid, realtime thermal cycler used for identifying DNA or RNA from prepared biological samples. Each instrument contains 16 independently programmable modules that can perform fourcolor, real-time fluorometric detection. Samples are amplified and measured in the SmartCycler's proprietary, scalable reaction tubes that are designed to optimize rapid thermal transfer and optical sensitivity.
The four channel optics in the SmartCycler Dx System enables the simultancous detection of four targets within a single sample (multiplex assays) by employing multiplex PCR techniques and real-time fluorescent technologies such as Molecular Beacons and TaqMan" probes, Amplifluor" and Scorpion® primers, and intercalating dyes.
The Smart GBS Assay includes an internal control (IC) to monitor the presence of inhibitors in the Polymerase Chain Reaction (PCR). The GBS primers and probe detect a unique region of the S. agalactiae chromosome.
A vaginal/rectal swab is collected and transported to the laboratory. Swab processing then proceeds by one of two methods (direct method or an optional enriched Lim broth method). The Smart GBS Assay includes the reagents required for sample processing (except for the Lims Broth) and the detection of the target GBS DNA. Once sample processing is completed, an aliquot is added to the reconstituted assay reagents. The resulting mixture is placed into the SmartTube, and then loaded into the SmartCycler Dx System for real-time PCR. For quality control, an external positive and negative run control are provided in the Smart GBS Assay for each run.
Here's a breakdown of the acceptance criteria and study information for the Cepheid Smart GBS™ Assay, based on the provided text:
Acceptance Criteria and Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity, specificity, or accuracy thresholds that the device had to meet. Instead, it presents the device's performance characteristics as determined from clinical studies and compares them to those of a predicate device, as well as emphasizing the overall safety, effectiveness, and substantial equivalence to the predicate. The "Performance Characteristics as determined in the Cepheid Clinical Studies (Protocols 105 and 108) as determined relative to culture" from Table 5-1 could be considered the reported device performance.
Table of Reported Device Performance:
| Protocol/Method | Performance Metric | Smart GBS™ Assay Performance |
|---|---|---|
| Protocol 105: Direct Method (Overall) | Sensitivity | 81.6% (95% CI = 75.3% - 86.9%) |
| Specificity | 96.4% (95% CI = 94.6% - 97.8%) | |
| Accuracy | 92.9% (95% CI = 90.9% - 94.6%) | |
| Prevalence | 23.9% (95% CI = 20.9% - 27.07%) | |
| Protocol 105: Direct Method (Intrapartum) | Sensitivity | 84.9% (95% CI = 76.0% - 91.5%) |
| Specificity | 97.2% (95% CI = 94.7% - 98.7%) | |
| Accuracy | 94.4% (95% CI = 91.7% - 96.4%) | |
| Prevalence | 22.7% (95% CI = 18.8% - 27.1%) | |
| Protocol 105: Direct Method (Antepartum) | Sensitivity | 78.3% (95% CI = 68.44% - 86.2%) |
| Specificity | 95.6% (95% CI = 92.5% - 97.7%) | |
| Accuracy | 91.2% (95% CI = 87.9% - 93.9%) | |
| Prevalence | 25.2% (95% CI = 20.8% - 30.0%) | |
| Protocol 108: Enriched Method (Antepartum Only) | Sensitivity | 98.7% (95% CI = 92.8% - 100.0%) |
| Specificity | 90.5% (95% CI = 85.9% - 93.9%) | |
| Accuracy | 92.5% (95% CI = 88.9% - 95.2%) | |
| Prevalence | 24.5% (95% CI = 19.8% - 29.7%) | |
| Reproducibility: Negative | Total % Agreement | 98.9% |
| Reproducibility: Weak Positive | Total % Agreement | 98.9% |
| Reproducibility: Positive | Total % Agreement | 100% |
| Reproducibility: Strong Positive | Total % Agreement | 100% |
| Reproducibility: Overall | Total % Agreement | 99.4% |
Study Details
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Sample sizes used for the test set and the data provenance:
- Direct Method Study (Test Set): 783 maternity subjects (363 antepartum, 420 intrapartum).
- Enriched Culture Study (Test Set): 306 antepartum maternity subjects.
- Data Provenance: Prospective investigational studies conducted at multiple institutions (six for direct method, three for enriched method) with maternity services in the United States.
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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. It refers to the "CDC-recommended culture technique" being performed in clinical laboratories.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The document does not describe a formal adjudication method involving multiple readers. The ground truth was established by the CDC-recommended culture technique which is a laboratory method, not typically adjudicated by multiple human experts in this context.
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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 done. This device is an in vitro diagnostic (IVD) assay that provides automated detection of GBS DNA; it is not an AI system that assists human readers in interpreting images or other data.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented is for the device in a standalone capacity ("algorithm only" in the context of an IVD assay where the "algorithm" is the real-time PCR detection and interpretation by the SmartCycler Dx System). The results are generated by the automated instrument, and while laboratory personnel perform sample preparation and load the device, the interpretation of the GBS detection itself is automated.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used was the CDC-recommended culture technique. This involves microbiological culture in selective broth medium (Lim broth), overnight incubation, subculture onto solid blood agar medium, and specific identification of GBS colonies with slide agglutination tests.
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The sample size for the training set:
- The document describes prospective investigational studies whose results are presented as the device's performance. It does not explicitly mention a separate "training set" for the purpose of machine learning or algorithm development. The analytical studies (analytical sensitivity, specificity) likely served for initial assay development and optimization, but a distinct pre-defined "training set" as understood in machine learning is not detailed.
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How the ground truth for the training set was established:
- As no distinct "training set" is described in the context of machine learning, this question is not fully applicable. However, for the analytical studies that would have informed the assay's development, the ground truth for detecting GBS strains (analytical sensitivity) was established using quantitated cultures of known Streptococcus agalactiae strains. For analytical specificity, known bacterial and yeast strains, and human DNA, were tested.
§ 866.3740
Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(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 § 866.9.