(134 days)
The BinaxNOW COVID-19 Ag Card is a lateral flow immunochromatographic assay for the rapid, qualitative detection of the SARS-CoV-2 nucleocapsid protein antigen directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory tract infection (i.e., symptomatic). The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the BinaxNOW COVID-19 Ag Card and followed up with a molecular test.
A negative test is presumptive and does not preclude SARS-CoV-2 infection; it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.
Positive results do not rule out co-infection with other bacteria or viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
The BinaxNOW COVID-19 Ag Card is an immunochromatographic membrane assay that uses antibodies to detect SARS-CoV-2 nucleocapsid protein from anterior nasal swab specimens. SARS-CoV-2 specific antibodies and a control antibody are immobilized onto a membrane support as two distinct lines and combined with other reagents/pads to construct a test strip. This test strip and a well to hold the swab specimen are mounted on opposite sides of a cardboard, book-shaped hinged test card.
To perform the test, an anterior nasal swab specimen is collected from the patient, 6 drops of extraction reagent from a dropper bottle are added to the top hole of the swab well. The patient sample is inserted into the test card through the bottom hole of the swab well, and firmly pushed upwards until the swab tip is visible through the top hole. The swab is rotated 3 times clockwise and the card is closed, bringing the extracted sample into contact with the test strip. Test results are interpreted visually at 15 minutes based on the presence or absence of visually detectable pink/purple colored lines. Results should not be read after 30 minutes.
The provided document is a 510(k) summary for the BinaxNOW COVID-19 Ag Card. It does not describe a study proving a device meets acceptance criteria in the manner typically associated with AI/ML-driven medical devices, which would involve measures like sensitivity, specificity, or AUC against a ground truth, often with human readers involved (MRMC studies).
Instead, this document describes the validation of an immunochromatographic assay (a rapid antigen test) for COVID-19. The "acceptance criteria" here are typically performance targets for analytical and clinical characteristics (e.g., Limit of Detection, cross-reactivity, Positive Percent Agreement, Negative Percent Agreement). The "study" refers to the analytical and clinical studies conducted to demonstrate these performance characteristics.
Therefore, the following response will interpret "acceptance criteria" as the performance benchmarks for a diagnostic assay and describe the validation studies for the BinaxNOW COVID-19 Ag Card based on the provided text.
Here's a breakdown of the information requested, interpreted in the context of a rapid antigen test (not an AI/ML device):
Acceptance Criteria and Device Performance for BinaxNOW COVID-19 Ag Card
The BinaxNOW COVID-19 Ag Card is a lateral flow immunochromatographic assay, not an AI/ML diagnostic device. Therefore, the "acceptance criteria" are based on the analytical and clinical performance characteristics typical for such an in-vitro diagnostic (IVD) device, rather than metrics like AUC, sensitivity/specificity of an AI algorithm, or human reader improvement with AI assistance.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Metric/Study | Performance Target (Implicit/Typical for IVDs) | Reported Device Performance |
|---|---|---|---|
| Analytical Performance | Limit of Detection (LOD) | Lowest virus concentration detected ≥ 95% of the time (e.g., 19/20 replicates positive) | USA-WA1/2020: 3.5 x 10³ TCID50/mL (70 TCID/swab) |
| B.1.1.529 (Omicron): 1.6 x 10³ TCID50/mL (32.06 TCID/swab) | |||
| WHO International Standard (NIBSC 21/368): 375 IU/mL (7.5 IU/swab), with 100% detection (20/20) at this concentration. | |||
| Analytical Reactivity (Inclusivity) | Detection of various SARS-CoV-2 strains at specified concentrations (all 5 replicates positive for a given concentration) | Detected 19 different SARS-CoV-2 variants (Alpha, Beta, Delta, Gamma, Iota, Italy-INMI1, Kappa, Zeta, Omicron variants including BA.2.3, BA.2.12.1, BA.2.75.5, BA.4.6, BA.5, BA.5.5, BF.5, BF.7, BQ.1, BQ.1.1, XBB, JN.1) at concentrations ranging from 8.75 x 10² TCID50/mL to 5.60 x 10⁴ TCID50/mL (or IU/mL for JN.1). | |
| Analytical Specificity (Cross Reactivity) & Microbial Interference | No cross-reactivity or interference with common respiratory pathogens/commensals. | No cross-reactivity or interference observed with 28 tested microorganisms (9 bacteria, 17 viruses, 1 yeast, pooled human nasal wash, and 4 Coronavirus HKU1 clinical specimens). | |
| In silico analysis for P. jirovecii showed very low potential for cross-reactivity. Possible susceptibility to SARS-CoV (due to homology) noted, but deemed low clinical likelihood. | |||
| High Dose Hook Effect | No hook effect at high viral concentrations. | No high dose hook effect observed up to 1.4 x 10⁶ TCID50/mL. | |
| Interfering Substances | No interference from specified endogenous or exogenous substances (e.g., common nasal medications, blood, mucin). | No effect on test performance found at specified concentrations for 25 substances (e.g., throat lozenges, various nasal sprays, hand sanitizer, blood, mucin). | |
| Reproducibility/Near the Cut Off | High agreement across sites for negative, low, moderate positive, and high negative samples. | Moderate Positive: 100% (135/135) overall agreement (95% CI: 97.2%-100.0%). | |
| Low Positive: 94.1% (127/135) overall agreement (95% CI: 88.7%–97.0%). | |||
| High Negative: 99.2% (132/133) overall agreement (95% CI: 95.9%-99.9%). | |||
| True Negative: 99.3% (134/135) overall agreement (95% CI: 95.9%-99.9%). | |||
| Clinical Performance | Positive Percent Agreement (PPA) | High PPA against a molecular comparator (RT-PCR) in symptomatic individuals. | Overall (Combined Studies): 86.9% (186/214) with 95% CI: 81.7%, 90.8% (within 5 days symptom onset). |
| Original Study: 81.6% (71/87) with 95% CI: 72.2%, 88.4%. | |||
| Omicron Study: 90.6% (115/127) with 95% CI: 84.2%, 94.5%. | |||
| Negative Percent Agreement (NPA) | High NPA against a molecular comparator (RT-PCR) in symptomatic individuals. | Overall (Combined Studies): 98.5% (384/390) with 95% CI: 96.7%, 99.3% (within 5 days symptom onset). | |
| Original Study: 98.6% (205/208) with 95% CI: 95.8%, 99.5%. | |||
| Omicron Study: 98.4% (179/182) with 95% CI: 95.3%, 99.4%. | |||
| Performance by Days Post Symptom Onset (DPSO) | Performance maintained within the specified window. | PPA ranged across DPSO: |
- Day 0: 69.23% (Omicron Study)
- Day 1: 94.12% (Original), 88.24% (Omicron)
- Day 2: 73.33% (Original), 97.22% (Omicron)
- Day 3: 76.00% (Original), 100.00% (Omicron)
- Day 4: 88.89% (Original), 66.67% (Omicron)
- Day 5: 100.00% (Original), 100.00% (Omicron) |
| | Invalid Rate | Low invalid rate. | 0.68% overall (5/730). |
| User/Environmental Factors | Flex Studies (Robustness) | Device performs accurately under various usage and environmental conditions. | Demonstrated robustness to usage variation and environmental factors. Identified that direct exposure of test strip to wet cleaning solutions or excessive glove powder may cause erroneous results, leading to specific instructions for use. |
2. Sample Sizes and Data Provenance (Clinical Studies)
- Clinical Test Set Sample Size:
- Study 1 (Original): 295 evaluable subjects.
- Study 2 (Omicron): 309 evaluable subjects.
- Combined Clinical Data: 604 evaluable nasal swabs from symptomatic patients (within 5 days of symptom onset).
- Data Provenance: Clinical studies were conducted within the United States.
- Study 1: November 2020 through March 2021 (when Delta and Omicron were dominant).
- Study 2: February 2022 to July 2022 (when Omicron and its variants were prevalent).
- Retrospective/Prospective: Both clinical studies were prospective.
3. Number of Experts and Qualifications for Ground Truth for Test Set
This type of diagnostic device (lateral flow immunoassay) does not typically utilize human experts in the same way an AI/ML device would for image interpretation or clinical diagnosis. For the BinaxNOW COVID-19 Ag Card, the ground truth for the clinical studies was established by a comparator molecular test (RT-PCR). The experts involved would be the laboratory personnel performing and interpreting the RT-PCR assays. Their specific qualifications are not detailed in this summary but are implicitly assumed to be standard for clinical laboratory professionals performing EUA-authorized RT-PCR tests.
4. Adjudication Method for the Test Set
Not applicable in the typical sense for an AI/ML study involving human interpretation. The comparator method (RT-PCR) serves as the reference standard. The document mentions for the serial testing study's composite comparator method that in cases of discordant RT-PCR results, a third RT-PCR test was performed, and the final result based on majority rule.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is a rapid antigen test, not an AI/ML system where human readers would interpret results "with vs. without AI assistance." The test is visually read by the user, and its performance is assessed against a molecular gold standard.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)
This question is not applicable in the context of this device. The BinaxNOW COVID-19 Ag Card is a manually read, qualitative visual assay. There is no AI algorithm to evaluate for standalone performance. The "performance" tables provided in the document (PPA and NPA) essentially represent the "standalone" performance of the rapid antigen test itself when interpreted visually.
7. Type of Ground Truth Used
- For Clinical Studies: The primary ground truth for clinical performance (PPA, NPA) was an FDA Emergency Use Authorized real-time Polymerase Chain Reaction (RT-PCR) assay for the detection of SARS-CoV-2.
- For Serial Testing Study: A composite comparator method was used, involving at least two highly sensitive EUA RT-PCRs. If discordant, a third RT-PCR was performed, and the final result was based on majority rule.
- For Analytical Studies: Ground truth was established by known concentrations of heat-inactivated SARS-CoV-2 virus or WHO International Standard for SARS-CoV-2 Antigen (NIBSC 21/368) for LoD and inclusivity studies, and known presence/absence of specific microorganisms for cross-reactivity.
8. Sample Size for the Training Set
This information is not applicable for this type of IVD device. The BinaxNOW COVID-19 Ag Card is a laboratory-developed lateral flow assay, not an AI/ML model that is 'trained' on data. Its 'training' is the fundamental assay development and optimization process, not a computational training set.
9. How the Ground Truth for the Training Set Was Established
Not applicable for this device type. The manufacturing process and quality control of the reagents and test strip govern its 'performance' characteristics, which are then analytically and clinically validated.
N/A