New Paper (Diagnostic): Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK

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Title: Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK

Please paste a link to the paper or a citation here:

Link: https://doi.org/10.1101/2023.07.24.23293072

What is the paper's Manubot-style citation?

Citation: doi:10.1101/2023.07.24.23293072

Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19

• limit of detection
• rapid antigen tests
• variants of concern
• test performance

Please note the publication / review status

• Pre-print
• New Peer-Reviewed Paper
• Peer-Reviewed Paper Pre-2020

Which areas of expertise are particularly relevant to the paper?

• virology
• epidemiology
• biostatistics
• immunology
• pharmacology

Questions to answer about each paper:

Please provide 1-2 sentences introducing the study and its main findings

For the WT, Alpha, Delta, Gamma and Omicron (BA.1) variants 22, 32, 29, 31 and 32 of the 34 Ag-RDTs evaluated met the World Health Organisations (WHO) target product profile (TPP), respectively. Of the 31 Ag-RDTs included for Omicron BA.5 evaluation 29 met the WHO TPP. Additionally, the LODs for samples spiked with Omicron BA.5 were significantly lower than all other VOCs included (p<0.001). In the retrospective clinical evaluation when comparing RNA copies/mL, the Ag-RDTs detected Alpha and Omicron (BA.1) more sensitively than the Delta VOC. Samples with high RT-qPCR Cts (Ct>25) resulted in reduced test sensitivities across all variants. We used linear regression to model the 50% and 95% LOD of clinical samples and observed statistically similar results for all tests. In the prospective clinical samples, the sensitivity was statistically similar for the Delta VOC 71.9% (CI 95% 53.3-86.6%) and Omicron VOC 84.4% (CI95% 75.3-91.2%).

Study question(s) being investigated:

What type of testing scenario is being considered?

Is it a screening test (used for individuals with no symptoms), diagnostic test (used for individuals with symptoms), or definitive test (used for individuals who have had previous positive test results on diagnostic or screening tests)?

Study population:

What is the model system (e.g., human study, animal model, cell line study)?

What is the sample size?

What is the "pre-test" probability of disease in the study population (i.e., what is the anticipated prevalence of the disease?)

For human studies, the following are related to the pre-test probability:

What countries/regions are considered?

What is the age range, gender, other relevant characteristics?

What is the setting of the study (e.g., random sample of school children, retirement communities, etc.)?

What other specific inclusion-exclusion criteria are considered?

Reference test:

What reference test is considered as a "gold standard" comparator for the test under investigation?

Test assignment:

How are the new and reference tests assigned?

Examples of assignment could include: Recruited individuals have initially undergone neither the new nor the reference test; individuals tested as positive or negative by the reference test undergo the new test; individuals who have undertaken the new test are assessed by the standard test.

Are there any other relevant details about the study design?

Depending on how individuals are chosen, the test may be biasing towards more sick or less sick individuals or very clear-cut positive/negative cases.
Any factors that would influence this bias should be included here.

Test conduct:

How were tests performed?

Describe technical details of assays used, when measurements were taken and by whom, etc. for both the new and standard tests.

Test Assessment

Describe how individuals are classified as positive or negative, e.g. if a threshold is used.

Is there evidence that the test is precise/reproducible when repeated more than once?

Are measurements complete?

For example: Do some participants undergo just one test (the new or the reference test)?
Are there individuals with inconclusive results?

Results summary:

What are the estimated sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV)?

Note that the PPV and NPV represent "post-test" probabilities of disease and are generally more meaningful than sensitivity and specificity.
Sometimes the post-test odds will be given instead.

What are the confidence bounds around these intervals?

Interpretation of results for study population:

How good is the test at ruling in or ruling out a disease based on the post-test probabilities?

Are there identified side affects of the test?

Is patient adherence to the test likely to be an issue?

Extrapolation of conclusions to other groups of individuals

How well is the test likely to work in populations with different pretest odds?

For example, if the prevalence is lower, then the PPV will also be lower, but the NPV will be higher.

How costly is the test?

How difficult is it to perform the test in different settings?

Could the test be combined with other existing tests?

Summary of reliability

1-2 sentences on concluding remarks, including summary of strengths, weaknesses, limitations.

Progress

Check off the components as they are completed. If the component is not applicable, check the box as well.

• 1-2 sentences introducing the study and its main findings
• Describe testing scenario
• Describe model system
• Sample size
• Describe prevalnce of disease
• Describe countries/regions are considered
• Describe age range, gender, other relevant characteristics
• Describe setting of the study
• Describe other specific inclusion-exclusion criteria
• Describe "gold standard"
• Describe how the new and reference tests assigned
• Describe other relevant details about the study design
• Describe how the tests were performed
• Describe how individuals are classified as positive or negative
• Describe if test is precise/reproducible
• Describe whether measurements are complete
• What are the estimated sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV)?
• What are the confidence bounds around these intervals?
• Describe post-test probabilities
• Describe side affects of the test
• Describe patient adherence
• Describe how it will extrapolate
• How costly is the test?
• How difficult is it to perform the test in different settings?
• Could the test be combined with other existing tests?
• Summary of reliability