(99 days)
The Binax NOW Streptococcus pneumoniae Urinary Antigen Test is a rapid immunochromatographic assay for the detection of S. pneumoniae antigen in urine specimens from patients with symptoms of pneumonia. It is intended to aid in the presumptive diagnosis of pneumococcal pneumonia in conjunction with culture and other methods.
The Binax Now Streptococcus pneumoniae Antigen Test is a urinary immunochromatographic membrane assay used to detect Streptococcus pneumoniae (S. pneumoniae) antigen in human urine. A test strip, containing gold-conjugated and immobilized anti-S. pneumoniae antibodies, and a swab well are mounted on opposite sides of a cardboard, book-shaped hinged test device. A swab is dipped into the urine to be tested and then inserted into the swab well. A single reagent is added to the swab well from a dropper bottle before closing the test device. Pneumococcal antigen present in the urine sample reacts to bind anti-S. pneumoniae antibody conjugated to gold. The resulting antigen-conjugate complexes are captured by immobilized anti-S. pneumoniae antibody, forming the Sample Line. Immobilized goat anti-rabbit IgG captures excess visualizing conjugate, forming the Control Line.
Here's a breakdown of the acceptance criteria and the study details for the Binax NOW® Streptococcus pneumoniae Urinary Antigen Test, based on the provided 510(k) notification:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for diagnostic devices like this are typically infered from the demonstrated performance that the FDA deems sufficient for market clearance, often in comparison to a predicate device. For this submission, the performance results are presented as the device's demonstrated capabilities.
Table 1: Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria (Inferred from Study) | Reported Device Performance (Retrospective Study) | Reported Device Performance (Prospective Multi-center Study) |
|---|---|---|---|
| Clinical Sensitivity | (Sufficiently high to aid in diagnosis, comparable to predicate or clinical need) | 86% (70.9% - 93.9% CI) | 90% (74.6% - 96.4% CI) |
| Clinical Specificity | (Sufficiently high to avoid false positives, comparable to predicate or clinical need) | 94% (90.9% - 96.0% CI) | 75% (69.3% - 81.5% CI) |
| Overall Accuracy | (Sufficiently high for clinical utility) | 93% (89.9% - 95.1% CI) | 77% (71.9% - 83.0% CI) |
| Analytic Sensitivity | Detects common pathogenic serotypes | 100% detection of 44 isolates representing 23 serotypes at 10^5 organisms/mL | Not separately reported for this criterion, but intrinsic to clinical performance |
| Analytic Specificity | No cross-reactivity with common related organisms/flora | No cross-reactivity with 143 of 144 organisms; 1 recognized cross-reactant (Streptococcus mitis) | Not separately reported for this criterion, but intrinsic to clinical performance |
| Interfering Substances | No interference from common urine components | No cross-reactivity with 19 common interfering substances (blood, cells, protein, glucose, turbidity) | Not separately reported, but included in overall performance |
| Reproducibility | Consistent results across different sites/operators | 99.4% agreement among 3 sites with negative, low positive, moderate positive, and high positive controls | Not separately reported, but assessed in reproducibility study |
| Quality Control | Procedural controls indicate test failure | Procedural control indicated failures when devices were intentionally made defective | Not separately reported, but assessed in QC study |
| Pneumococcal Vaccine Impact | Acceptable impact of vaccine on test results | 13% tested positive within 30 hours of vaccination, then negative by 48 hours. Product labeling will warn not to test within 48 hours of vaccination. | Not separately reported, but assessed in vaccine study |
Study Details
2. Sample Sizes and Data Provenance for Test Set:
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Retrospective Study:
- Total Samples: 373 urine specimens
- Positive Cases: 35 urine specimens from blood culture positive pneumococcal pneumonia patients.
- Negative Cases: 338 urine specimens from presumed S. pneumoniae negative patients (28 from bacteremic patients, 4 from empyema, 53 from pneumonia, 153 from UTIs, 100 from no known infection).
- Provenance: Not explicitly stated, but likely from a diverse patient population given the varied sources of negative samples. Described as "freshly collected and characterized frozen urine specimens," suggesting a mix of past and potentially more recent collections. This indicates a retrospective study.
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Multi-center Prospective Study:
- Total Samples: 215 urine specimens
- Patients: Hospitalized or out-patients presenting with lower respiratory symptoms or sepsis, suspected of pneumococcal pneumonia.
- Provenance: "separate multi-center prospective study." This indicates a prospective study from multiple clinical sites. Country of origin not specified.
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Analytic Sensitivity: 44 isolates representing 23 Streptococcus pneumoniae serotypes.
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Analytic Specificity (Cross-Reactivity): 144 potential cross-reactants (organisms associated with pneumonia and urogenital tract flora).
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Interfering Substances: 19 urine specimens with potentially interfering substances (e.g., blood, WBC, protein, glucose, turbidity).
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Pneumococcal Vaccine: Number of study participants not explicitly stated, but implies a group received the vaccine.
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Reproducibility: A panel of coded specimens (negative, low positive, moderate positive, high positive controls) used at 3 separate sites. Number of specimens in the panel is not specified.
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Quality Control: 20 devices with induced defects.
3. Number of Experts and Qualifications for Ground Truth:
- The document does not explicitly mention the use of experts to establish a "ground truth" through consensus or review for the clinical studies.
- The ground truth for the clinical studies relies on blood culture results (see point 7).
- For analytic sensitivity, the "known Streptococcus pneumoniae serotypes" imply a microbiological expert's identification and characterization.
- For analytic specificity, the "known cross-reactants grown in culture" implies microbiological identification.
4. Adjudication Method for Test Set:
- None explicitly stated for the clinical performance studies.
- The ground truth for clinical cases (blood culture positive/negative) is an objective laboratory result, not typically subject to adjudication by multiple human readers for diagnostic accuracy.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a MRMC comparative effectiveness study was not conducted.
- The study focuses on the standalone performance of the device against an objective standard (blood culture), not on how human readers' performance improves with or without the device's assistance.
6. Standalone Performance Study:
- Yes, a standalone (algorithm only without human-in-the-loop performance) study was performed. The entire clinical performance section (Clinical Sensitivity and Specificity) describes the performance of the Binax NOW® test independently from human interpretation beyond reading the visual result.
7. Type of Ground Truth Used:
- Blood Culture: For both the retrospective and multi-center prospective clinical studies, the primary ground truth used to determine the presence or absence of S. pneumoniae infection was blood culture results.
- Microbiological Culture/Identification: For analytic sensitivity, the ground truth was the presence of known S. pneumoniae serotypes at a specified concentration via culture. For analytic specificity, it was the identification of specific microbial species/isolates.
- Defined Chemical/Cellular Composition: For interfering substances, the ground truth was the known presence of elevated levels of specific substances (e.g., blood, WBC, protein, glucose, turbidity).
8. Sample Size for the Training Set:
- The document does not specify a training set size. This is common for diagnostic device submissions where the device's design is often based on fundamental scientific principles (e.g., antibody-antigen binding) and optimized through iterative development rather than a distinct machine learning "training" phase with a large, labeled dataset in the way an AI algorithm might have. The studies described are performance validation studies.
9. How Ground Truth for Training Set Was Established:
- As no explicit training set is identified, the method for establishing its ground truth is not applicable/not documented in this submission. The "performance verification" used "freshly collected and characterized frozen urine specimens," which were then used in the retrospective study, suggesting these types of samples were used in the development and initial validation process without being formally labeled as a "training set." The development of the assay itself would have involved establishing the optimal antibody pair and concentrations through laboratory testing against known positive and negative samples.
§ 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.