(90 days)
The BinaxNOW COVID-19 Antigen Self Test is a visually read lateral flow immunoassay intended for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal (nares) swab specimens from individuals with signs and symptoms of COVID-19. This test is for non-prescription home use by individuals aged 15 years or older testing themselves, or adults testing individuals aged 2 years or older.
All negative results are presumptive. Symptomatic individuals with an initial negative test result must be re-tested once between 48 and 72 hours after the first test using either an antigen test or a molecular test for SARS-CoV-2. Negative results do not preclude SARS-CoV-2 infections or other pathogens and should not be used as for treatment.
Positive results do not rule out co-infection with other respiratory pathogens.
This test is not a substitute for visits to a healthcare provider or appropriate follow-up and should not be used to determine any treatments without provider supervision. Individuals who test negative and experience continued or worsening COVID-19 like symptoms, such as fever, cough and/or shortness of breath, should seek follow up care from their healthcare provider.
The performance characteristics for SARS-CoV-2 were established from November, 2020 to July, 2022, when SARS-CoV-2 Delta and Omicron were dominant. Test accuracy may change as new SARS-CoV-2 viruses emerge. Additional testing with a lab-based molecular test (e.g., PCR) should be considered in situations where a new virus or variant is suspected.
The BinaxNOW COVID-19 Antigen Self Test is an immunochromatographic membrane assay that uses highly sensitive antibodies to detect SARS-CoV-2 nucleocapsid protein from 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, a 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 ugh 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 is closed, bringing the extracted sample into contact with the test strip. Test results are interpreted visually at 15 minutes based on the presence of visually detectable pink/purple colored lines. Results should not be read after 30 minutes.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for BinaxNOW COVID-19 Antigen Self Test
The document outlines acceptance criteria generally through reported performance metrics for various analytical and clinical studies. Explicit "acceptance criteria" are not given as pass/fail thresholds in the same way that a test specification would be. Instead, the reported performance serves to demonstrate the device's capabilities.
1. Table of Acceptance Criteria (Implied) and Reported Device Performance
| Acceptance Criteria Category (Implied) | Reported Device Performance |
|---|---|
| Analytical Performance | |
| Precision | Lot 1: 5X LoD (100%), 1X LoD (100%), High Negative (100%), Negative (100%) |
| Lot 2: 5X LoD (100%), 1X LoD (97.8%), High Negative (100%), Negative (100%) | |
| Lot 3: 5X LoD (100%), 1X LoD (95.8%), High Negative (100%), Negative (100%) | |
| Limit of Detection (LoD) | USA-WA1/2020: $3.5 \times 10^3$ TCID50/mL (70 TCID50/swab) |
| B.1.1.529 (Omicron): $1.6 \times 10^3$ TCID50/mL (32.06 TCID50/swab) | |
| International Standard for SARS-CoV-2 Ag (NIBSC 21/368): 375 IU/mL (7.5 IU/swab) | |
| Analytical Reactivity (Inclusivity) | Detected all tested SARS-CoV-2 strains (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 specified concentrations (e.g., Alpha at $2.80 \times 10^5$ TCID50/ml, Omicron (BA.5.5) at $8.80 \times 10^2$ TCID50/ml). |
| Analytical Specificity (Cross-Reactivity/Interference) | No cross-reactivity or interference observed with 29 common commensal and pathogenic microorganisms (9 bacteria, 17 viruses, 1 yeast, pooled human nasal wash) at specified concentrations (1 x $10^6$ CFU/mL for bacteria/yeast, 1 x $10^5$ TCID50/mL for viruses), both in absence and presence of SARS-CoV-2 at 3xLoD. |
| High Dose Hook Effect | No high dose hook effect observed up to 1.4 x $10^6$ TCID50/mL of inactivated SARS-CoV-2 virus. |
| Interfering Substances | No effect on test performance by 25 specified substances (e.g., throat lozenges, various nasal sprays, hand sanitizer/soap, blood, mucin, common medications) at specified concentrations. |
| Usability Performance | |
| Usability Study (Procedural Execution) | 98% correct execution of procedural steps by lay users. |
| Usability Study (Impact of Errors) | 100% of participants produced a valid result and interpreted their test result correctly. |
| Lay User Readability | Overall (n=30): Positive Control (100%), Positive 2xLoD (83%), Positive 1.5xLoD (67%), Positive ≤1xLoD (60%), Negative Control (97%), Invalid 1 (97%), Invalid 2 (97%), Invalid 3 (100%), Invalid 4 (97%). Performance decreases with faint sample lines and is influenced by age and visual capabilities. |
| Clinical Performance | |
| Overall/Combined (within 5 days of symptom onset) | Positive Agreement (Sensitivity): 86.9% (95% CI: 81.7, 90.8) (186/214) |
| Negative Agreement (Specificity): 98.5% (95% CI: 96.7, 99.3) (384/390) | |
| Invalid Rate: 0.68% (5/730) | |
| Original Study (Nov 2020 - Mar 2021) | Positive Agreement: 81.6% (95% CI: 72.2, 88.4) (71/87) |
| Negative Agreement: 98.6% (95% CI: 95.8, 99.5) (205/208) | |
| Overall Agreement: 93.6% (95% CI: 90.2, 95.8) | |
| Invalid Rate: 0.76% (3/397) | |
| Omicron Study (Feb 2022 - Jul 2022) | Positive Agreement: 90.6% (95% CI: 84.2, 94.5) (115/127) |
| Negative Agreement: 98.4% (95% CI: 95.3, 99.4) (179/182) | |
| Invalid Rate: 0.61% (2/327) | |
| PPA Stratified by Days Post Symptom Onset (DPSO) | Varied by day and study; e.g., Original Study Day 1: 94.12%, Omicron Study Day 3: 100.0%. |
| Serial Testing PPA | Symptomatic on First Day of Testing (2 Tests): Day 0: 59.6% (34/57), Day 2: 93.5% (58/62), Day 4: 94.8% (55/58) |
| Symptomatic on First Day of Testing (3 Tests): Day 0: 92.2% (47/51), Day 2: 98.3% (59/60), Day 4: 98.1% (53/54) |
2. Sample Sizes and Data Provenance
Test Set (Clinical Studies):
- Total for Clinical Performance: 604 nasal swabs from symptomatic patients within 5 days of symptom onset.
- Study 1 (Original Study): 295 subjects (resulting in 295 evaluable samples).
- Study 2 (Omicron Study): 309 subjects (resulting in 309 evaluable samples).
- Serial Testing Study: 5,600 eligible participants for analysis, out of 7,361 enrolled. 154 tested positive for SARS-CoV-2 infection by RT-PCR.
- Provenance: All subjects were from the United States.
- Study 1: Prospective, conducted from November 2020 through March 2021 across five investigational sites (when Delta and Omicron were dominant).
- Study 2 (Omicron Study): Prospective, "all comers, real world," conducted from March 2022 to July 2022 at a high-volume COVID community testing site (when Omicron and its variants were prevalent). Led by Johns Hopkins Medicine in collaboration with the University of Maryland Medical Center and Maryland Department of Health.
- Serial Testing Study: Prospective, decentralized clinical study conducted between January 2021 and May 2022 as part of the Rapid Acceleration of Diagnostics (RADx) initiative from NIH, with broad geographical representation in the U.S.
Test Set (Usability Studies):
- Lay User Readability Study: 30 users across various age ranges and with and without vision impairments.
3. Number of Experts and Qualifications for Ground Truth
- The document does not explicitly state the number of experts used to establish the ground truth for the test set in the clinical studies.
- The ground truth in the clinical studies was established using FDA Emergency Use Authorized real-time Polymerase Chain Reaction (RT-PCR) assays for the detection of SARS-CoV-2. These are laboratory-based molecular tests, implying the involvement of qualified laboratory personnel (e.g., medical technologists, molecular diagnosticians) experienced in performing and interpreting these assays, but specific qualifications are not detailed. In the serial testing study, the composite comparator method involved "at least two highly sensitive EUA RT-PCRs" and a third if discordant, performed by presumably qualified laboratory personnel.
4. Adjudication Method for the Test Set
- Clinical Studies (Primary Performance): No explicit adjudication method is described for discrepancies between the BinaxNOW test and the comparator RT-PCR. The RT-PCR is considered the gold standard (comparator method).
- Serial Testing Study (Composite Comparator): A form of adjudication was used for the molecular comparator itself: "If results of the first two molecular tests were discordant a third highly sensitive EUA RT-PCR test was performed, and the final test result was based upon the majority rule." This is a 2+1 adjudication method for establishing the RT-PCR ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was conducted to evaluate human readers with and without AI assistance. The BinaxNOW COVID-19 Antigen Self Test is a visually read lateral flow immunoassay, interpreted directly by the user, and does not involve AI assistance for result interpretation.
6. Standalone (Algorithm Only) Performance Study
- No standalone (algorithm only) performance study was conducted. As a visually read immunoassay, the device relies on human interpretation. The "lay user readability study" specifically evaluates human interpretation, not an automated algorithm.
7. Type of Ground Truth Used
- Clinical Studies: The primary ground truth for clinical performance was established using FDA Emergency Use Authorized real-time Polymerase Chain Reaction (RT-PCR) assays for SARS-CoV-2.
- Analytical Studies (LoD, Reactivity, Specificity): The ground truth was based on defined concentrations of inactivated SARS-CoV-2 virus strains, international standards, or specific microbial/substance concentrations, as prepared by qualified laboratory personnel.
8. Sample Size for the Training Set
- The document describes performance evaluation studies (test sets) for the BinaxNOW device. It does not provide information about a "training set" in the context of machine learning, as this is a traditional in-vitro diagnostic device that relies on chemical reactions and visual interpretation, not an AI/ML-based device.
9. How the Ground Truth for the Training Set was Established
- As there is no mention of an AI/ML training set, this information is not applicable and not provided in the document.
N/A