(168 days)
The Sofia® Strep A+ FIA detects Group A Streptococcal antigens from patients with signs and symptoms of pharyngitis, such as sore throat. All negative test results should be confirmed by bacterial culture because negative results do not preclude Group A Strep infection and should not be used as the sole basis for treatment. The test is intended for professional and laboratory use as an aid in the diagnosis of Group A Streptococcal infection.
The Sofia Strep A FIA employs immunofluorescence technology that is used with the Sofia analyzer (Sofia) to detect Group A Streptococcal antigen. The Sofia Strep A FIA involves the extraction of the antigenic components of the Group A Streptococcus (GAS) bacteria. The patient's swab sample is placed in the Reagent Tube containing the Reagent Solution, during which time the bacterial antigens are extracted, making them more accessible to the specific antibodies. An aliquot of the extracted sample is dispensed into the Cassette sample well. From the sample well, the sample migrates through a test strip containing various unique chemical environments. If Group A Streptococcal antigens are present, they will be bound by antibodies coupled to fluorescent microparticles that migrate through the test strip. The fluorescent microparticles containing bound antigen will be captured by antibodies at a defined location on the test strip where they are detected by Sofia. If antigens are not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia. Note: The Cassette, now containing the sample, is placed directly inside Sofia for automatically timed development (WALK AWAY Mode). Sofia scans, measures, and interprets the immunofluorescent signal using method-specific algorithms. Sofia will display the test results (Positive, Negative, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected, or transmitted via an LIS connection.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device: Sofia® Strep A+ FIA
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" numerically for sensitivity and specificity. However, based on the performance study results, the implied acceptance criteria would be the statistically significant ranges demonstrated by the device.
| Metric | Acceptance Criteria (Implied from performance) | Reported Device Performance (95% CI) |
|---|---|---|
| Sensitivity | > 89.1% (lower bound of 95% CI) | 93.7% (89.1%-96.5%) |
| Specificity | > 92.4% (lower bound of 95% CI) | 94.4% (92.4%-95.9%) |
| PPV | Not explicitly defined, but reported | 81.2% |
| NPV | Not explicitly defined, but reported | 98.3% |
| Reproducibility Inter-laboratory (Negative) | > 95.9% (lower bound of 95% CI) | 100% (95.9-100.0%) |
| Reproducibility Inter-laboratory (High Negative) | > 82.1% (lower bound of 95% CI) | 90% (82.1-94.7%) |
| Reproducibility Inter-laboratory (Low Positive) | > 78.1% (lower bound of 95% CI) | 87% (78.1-92.2%) |
| Reproducibility Inter-laboratory (Mod Positive) | > 95.9% (lower bound of 95% CI) | 100% (95.9-100.0%) |
| Reproducibility Intra-laboratory (Overall Site 1) | > 89.5% (lower bound of 95% CI) | 95% (89.5-97.7%) |
| Reproducibility Intra-laboratory (Overall Site 2) | > 87.4% (lower bound of 95% CI) | 93% (87.4-96.6%) |
| Reproducibility Intra-laboratory (Overall Site 3) | > 88.5% (lower bound of 95% CI) | 94% (88.5-97.2%) |
| Limit of Detection (LoD) | Not explicitly defined as a single criterion, but values must be provided | Ranged from 2.76E+03 to 8.13E+03 cfu/test (for 3 strains) |
| Analytical Reactivity | 100% detection of tested strains at specified concentration | All 21 tested Streptococcus pyogenes strains detected at 1.74E+04 cfu/test. |
| Analytical Specificity (Cross-Reactivity) | No cross-reactivity with non-GAS organisms/viruses at specified concentrations | None of the 61 non-Group A Streptococcus bacterial and fungal microorganisms, and 26 viral isolates showed any sign of cross-reactivity. |
| Interfering Substances | No interference at specified concentrations | Most substances did not interfere. Nacho Flavor Doritos interfered at 25% w/v and Fresh Whole Blood interfered at 100 µL/swab. Bovine submaxillary mucin interfered at 28.7 mg/mL. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Performance Study: 851 patients.
- Data Provenance: Retrospective, collected during 2014 from 7 distinct CLIA-waived sites in various geographical regions within the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their qualifications for interpreting the ground truth (bacterial culture and PCR). However, it mentions:
- "A central Reference Laboratory" conducted the bacterial culture and PCR. This implies qualified laboratory personnel.
4. Adjudication Method for the Test Set
The primary comparison was against standard bacterial culture. For discordant results between the Sofia Strep A+ FIA and culture, an "FDA-cleared molecular device" (RT-PCR assay) was used for resolution.
- Method: Initial comparison of Sofia Strep A+ FIA to bacterial culture.
- Discordant Resolution: For specimens where Sofia Strep A+ FIA and culture disagreed, an FDA-cleared molecular device (PCR) was used to resolve the discrepancy. This is a 2-step adjudication approach (initial culture, then PCR for discrepancies).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not done. This study is for a diagnostic device (FIA) that measures antigens, not an AI-powered image analysis system that would assist human readers in interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the clinical performance study directly evaluated the "rapid FIA test result" from the Sofia Strep A+ FIA against the ground truth. The device itself (Sofia Strep A+ FIA with the Sofia analyzer) provides the result (Positive, Negative, or Invalid) and automatically interprets the immunofluorescent signal using method-specific algorithms, thus representing a standalone performance evaluation.
7. The Type of Ground Truth Used
The ground truth for the clinical performance study consisted of:
- Bacterial Culture: Throat swabs were streaked on a sheep blood agar plate (SBA) and cultured for up to 48 hours.
- Molecular (PCR): An FDA-cleared Group A Streptococcus RT-PCR assay was used to resolve discordant results between the device and primary culture. This is a combination of culture and a highly sensitive molecular method.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" sample size. This type of device (immunofluorescence assay) doesn't typically undergo a machine learning training phase in the same way an AI-powered diagnostic algorithm would. The development of its "method-specific algorithms" would be based on analytical studies (LoD, cross-reactivity, precision) to define positive/negative thresholds rather than a distinct training dataset of patient samples.
9. How the Ground Truth for the Training Set Was Established
As noted above, a traditional "training set" with ground truth in the context of machine learning is not applicable here. The "method-specific algorithms" in the Sofia analyzer would have been developed and validated based on extensive analytical studies to establish appropriate thresholds for signal detection and interpretation. These analytical studies involved:
- Serial dilutions of known concentrations of Streptococcus pyogenes strains (for LoD).
- Testing against known non-Group A Streptococcus organisms and various viruses at specific concentrations (for analytical specificity/cross-reactivity).
- Testing with potential interfering substances at defined concentrations.
These analytical studies establish the performance characteristics that dictate how the device's inherent algorithms classify a result, rather than a separate "training set" of patient data.
§ 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.