(85 days)
The Focus Diagnostics Simplexa™ Group A Strep Direct assay is intended for use on the 3M Integrated Cycler for the in vitro qualitative detection of Group A Streptococcus (GAS) from throat swabs collected from human patients with signs and symptoms of pharyngitis, such as sore throat. This test is intended for use as an aid in the diagnosis of GAS infection. The assay is intended for use in hospital, reference, or state laboratory settings. The device is not intended for point-of-care use.
The Simplexa™ Group A Strep Direct assay system is a real-time PCR system that enables the direct amplification and qualitative detection of Group A Strep bacterial DNA from throat swabs that have not undergone a nucleic acid extraction. The system consists of the Simplexa™ Group A Strep Direct assay, the 3M Integrated Cycler (with Integrated Cycler Studio Software), the Direct Amplification Disc (DAD) and associated accessories.
In the Simplexa™ Group A Strep Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify Group A Strep bacterial DNA and the Internal Control (DNA IC). The assay targets a conserved region of Group A Strep (pyroqenic exotoxin B gene) to identify this bacteria in the specimen. The DNA IC is used to detect PCR failure and/or inhibition.
Here is a summary of the acceptance criteria and study information for the Simplexa™ Group A Strep Direct device, based on the provided text:
Acceptance Criteria and Device Performance for Simplexa™ Group A Strep Direct
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the clinical study's sensitivity and specificity. However, the performance characteristics of the device and its predicate device are compared. For the purpose of this response, we will consider the reported "Performance Characteristics" of the predicate device as a benchmark or implicit acceptance criteria, though the device has slightly lower specificity than the predicate.
| Metric | Predicate Device Performance / Benchmark (Simplexa™ Group A Strep Direct K133883) | Simplexa™ Group A Strep Direct Performance (Clinical Prospective Study) |
|---|---|---|
| Sensitivity | 96.5% (95% CI: 91.3% - 98.6%) | 97.4% (152/156) (95% CI: 93.6% to 99.0%) |
| Specificity | 98.0% (95% CI: 97.0% - 98.6%) | 95.2% (1139/1196) (95% CI: 93.9% to 96.3%) |
| Positive Predictive Value (PPV) | Not explicitly stated for predicate in comparison table. | 72.7% (152/209) (95% CI: 66.3% to 78.3%) |
| Negative Predictive Value (NPV) | Not explicitly stated for predicate in comparison table. | 99.7% (1139/1143) (95% CI: 99.1% to 99.9%) |
Note: The device's sensitivity (97.4%) is numerically higher than the predicate's (96.5%), and its specificity (95.2%) is numerically lower than the predicate's (98.0%). The FDA's substantial equivalence determination implies these results were acceptable.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 1352 evaluable samples.
- Data Provenance: Prospectively collected from four geographically diverse sites. The country of origin is not explicitly stated but can be inferred to be the USA given the FDA submission document.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not mention the use of "experts" in the traditional sense (e.g., radiologists) for establishing ground truth. Instead, for the clinical prospective study, the comparator culture method was used as the primary reference for ground truth, and discrepant results were further analyzed.
4. Adjudication Method for the Test Set
The primary comparison was against a "comparator culture method" performed at one central laboratory.
For discrepant analysis, a "validated bidirectional sequencing assay" was performed.
- 46 out of 57 samples where Simplexa™ was Positive and Culture was Not Detected were confirmed as Group A Strep Positive by sequencing.
- 2 out of 4 samples where Simplexa™ was Not Detected and Culture was Detected were confirmed as Group A Strep Positive by sequencing.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is a molecular diagnostic assay (PCR-based system) for the qualitative detection of Group A Streptococcus, not an imaging device requiring human reader interpretation. Therefore, the concept of improving human readers with AI assistance is not applicable here.
6. Standalone Performance Study
Yes, a standalone performance study (algorithm only without human-in-the-loop performance) was performed. The entire clinical prospective study and analytical studies evaluate the device's performance independently. The device's results are compared directly against a culture method and a sequencing assay, not against human interpretation of the device's output.
7. Type of Ground Truth Used
- Primary Ground Truth: Comparator culture method.
- Confirmatory Ground Truth for Discrepancies: Validated bidirectional sequencing assay.
8. Sample Size for the Training Set
The document describes the performance of the device and does not explicitly mention a "training set" in the context of machine learning. The studies described are validation studies (e.g., Limit of Detection, Analytical Reactivity, Cross Reactivity, Interference, Clinical Prospective Study) that assess the device's performance characteristics. If the device's internal algorithms underwent a "training" phase during its development, the details are not provided in this regulatory summary.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is mentioned for an algorithm, the method for establishing its ground truth is not provided. The document focuses on the validation of the finalized device.
§ 866.2680
Streptococcus spp. nucleic acid-based assay.(a)
Identification. AStreptococcus spp. nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify variousStreptococcus spp. nucleic acids extracted directly from clinical specimens. The device detects specific nucleic acid sequences for organism identification. 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 II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate.
(6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.