PONE-D-21-14542

Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program

PLOS ONE

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Academic Editor

PLOS ONE

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Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: In presenting argument in the introduction that antibody testing can be an alternative for RT-CPR, it may be helpful to note that the test evaluates different things: active infection vs history of infection (including current), with different delays between tests being positive (longer for serology). This reviewer agrees that serology can be a very attractive alternative for reasons cited by the authors, but additional caveats other than SN (sensitivity) and SP (specificity) related to meaning of the test in terms of inference of onset of incident infection should be clearly presented.

Can you please be clearer in the introduction how your approach is “in contrast to other studies which use a PCR-test as a reference to estimate sensitivity and specificity of an Ag-Test4”?

One alternative to Bonferroni correction that seems appealing to this reviewer is to model rate of positive tests using binomial regression with random effect of county, and maybe some fixed effects that can account for rate of positive tests, such as numbers quarantined per county, positivity rates from Phase 1, age structure, economic indicators, percent of county tested, outdoor temperature, count/proportion of outdoor test sites, date of test (the usual confounders in epidemiology that can affect both willingness to test and chance of having been infected plus those mentioned in the discussion by the authors). The fixed intercept of the model would overall rate of positive tests and can be made county-specific through use of other random and fixed covariates; upper percentile of these modelled estimates can be used authors did with their Bonferroni-adjusted confidence interval. One may be also tempted to model spatial correlation, if descriptive statistics support its existence.

Instead of just giving upper bound of 95%CI, it would be more informative to give both the estimate per county and associated standard error. This should allow anyone to estimate different percentile if for their purposes 97.5% is not appropriate. This may already be in the supplemental materials, so maybe this is just a matter of pointing the reader in the right direction.

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Reviewer #1: Yes: Igor Burstyn

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Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program

PONE-D-21-14542R1

Dear Dr. Posch,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Etsuro Ito

Academic Editor

PLOS ONE