PONE-D-23-05526Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocolPLOS ONE

Dear Dr. Green,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR:The protocol is relevant and will certainly simplify COVID-19 surveillance activities especially in low resource settings where access to highly sophisticated PCR tests are rarely available.Please address all comments provided by both reviewers. For reviewer 1, try to adjust your protocol's rational and methodology by making them more explicit to avoid any potential ambiguity. The revision should be minimal. 

Please also ensure that your revised submission fully complies with PLOS ONE publication criteria.

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We look forward to receiving your revised manuscript.

Kind regards,

Ibrahim Jahun, MD, MSC, PhD

Academic Editor

PLOS ONE

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2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

3. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: No

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This article does not say anything about Co-Infections to COVID-19. Inclusion criteria should be elaborated with appropriate controls like, gold standard test controls to rule out possible chances of cross reactivity/ co-infectivity. If there are any cases of co-infections along with COVID-19 then whether this participant will be excluded or any other statistical methodology to analyze these populations? This criterion can increase the sensitivity/ Specificity of screening test.

Reviewer #2: 1- Study populations (line 108) Consideration for age range of 7 and above: Although the protocol has received ethical reviews and approvals, it might be necessary to consider limiting the study to adolescents, youths, and adults (aged 14 and above) this will limit the need for supervision of sample collection and self-testing processes by household members at home, to minimize potentials for spread of infections at household level during the process as part of infection prevention. Alternatively, the protocol has to detail how infection prevention will be enhanced through training and provision of PPEs to care givers who will supervise minors enrolled into this study, and what to do in case of exposure

2- Index cases (Line 109 – 110): indicate what method(s) of test was used or will be used for COVID-19 Positive index cases.

3- Randomization (line 119 – 121): the sentence indicated that contacts of index cases will be randomized, whereas randomization is only at the level of the index cases. This should be rephrased to show this. The use of randomization for the contacts of index cases throughout the rest of the protocol need to be rephrased accordingly.

4- Line 131: Will study participants receive the same brand and batch of self-test kits for consistency? This should be included in the narrative

5- Line 132: Include how the study participants will be contacted in this segment of the protocol – by physical visits, phone calls, WhatsApp (as indicated further down in the protocol), email or a mix

6- Line 149: Indicate if 3 results will be for 3 consecutive days or otherwise, and what is the rational for using 3 results out of 10-day daily testing?

7- Line 150: indicate if one-time Ag-RDT test of close contacts of index case within 2 days of symptoms onset, or within 7 days of positive results is the standard practice in Brazil – as proposed for the control group

8- While training of study participants is implied in the protocol, it would be necessary to include, as part of the methods, that training on standard sample collection, self-testing procedure and interpretation of results, as well as safety precautions and infection prevention and control methods, would be provided and by whom, and at what point of the study

9- Line 18 – 160: will the study participants be part of the focused group discussions – who are the stakeholders in this case? Will the FGD be conducted prior to enrollment into the study or at the completion of 10-day monitoring?

10- The protocol did not include any quality check or process for reviewing the Self-testing procedures and validating results. A quality control measure is essential to avoid over reporting of positive test results or under reporting. This could be done by review of captured images of the test strips or other alternative methods.

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Reviewer #1: Yes: Manoj A R

Reviewer #2: Yes: McPaul I.J. Okoye

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Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol

PONE-D-23-05526R1

Dear Dr. Green,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Ibrahim Jahun, MD, MSC, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Authors have addressed the issues and observations made in the first iteration, and have made further improvements to the manuscript.

The following minor improvements are further recommended:

1- It would be necessary to include measures the authors would implement to minimize potentials for viral transmission to household members (infection prevention and control measures) at the household level during self testing for all study participants in the the intervention arm, especially for children requiring supervision by household members. This could be included in the safety or ethical consideration sections

2- In figure 2 and Ethical Consideration: Authors to clarify what decision would be made if the Professional Ag.RDT conducted at the enrollment stage was positive - will study participants in the control arm who tested positive be linked to care? This should be included in the ethical consideration section.

3- Authors to clarify what decision would be made for study participants in the Intervention ARM, who had a positive result based on Professional Ag.RDT at enrolment stage, but negative results following 10 days of serial Self-Testing (ST) without any significant testing procedure error, would these category of study participants be linked to care as per Brazil's standard guidelines?

4- Authors may wish to consider including study participants inclusion and exclusion criteria sections in the protocol to facilitate understanding

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: McPaul I.J. Okoye

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