PONE-D-21-11468

Theory-Based Immunization Health Education Intervention in Improving Child Immunization Uptake Among Antenatal Mothers Attending Federal Medical Center In Nigeria: A Study Protocol for a Randomized Controlled Trial.

PLOS ONE

Dear Dr. Mohd Zulkefli,

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.

Please submit your revised manuscript by Oct 01 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Stephen R. Walsh, MDCM

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. PLOS ONE does not copy edit accepted manuscripts (https://journals.plos.org/plosone/s/criteria-for-publication#loc-5). To that effect, please ensure that your submission is free of typos and grammatical errors.

3. Please ensure that you refer to Figure 1 in your text as, if accepted, production will need this reference to link the reader to the figure

Additional Editor Comments (if provided):

Thank you for submitting your protocol to PLoS One. Our reviewers had a large number of concerns with the submission, but are ultimately supportive of the clinical trial proposed as it answers an important medical need. If you believe you can respond adequately to the concerns addressed, we invite you to resubmit the protocol.

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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

Reviewer #3: No

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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: Partly

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: No

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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: The authors plan an important study. The manuscript submitted requires revision to fully illustrate the rationale for selecting the study design and the particular intervention as well as how it differs from the standard of care. Overall, the manuscript would benefit from more concise presentation of more detailed information, most especially about the methodology planned.

Specifically:

1/Background -

a/Too lengthy; reduce by about 1/3 in length.

b/Focus of the narrative drifts; concentrate on the immunization performance in the selected state, the reasons behind that, how the proposed intervention addresses the gaps and then state the research questions posed.

2/Study design -

a/Explain how this design is the most appropriate to address the research questions.

b/Blinding - It is not possible to blind the participants to the assigned study group because they will know if they participate in the group intervention. Please rectify the description of blinding.

c/Contamination; explain how women who have receive the intervention will be stopped from influencing immunization seeking behavior of the control women.

3/Intervention -

a/Explain the development of the intervention and if it has been tested previously to convince the reader that it is appropriate and potentially feasible. One concern I have is the duration of the single session; in my experience, women in late pregnancy often are not comfortable to spend the whole day at the clinic and should be resting for some of the day.

b/Itemise the components of the intervention. State whether the transport reimbursement and Pampers are considered elements of the intervention.

c/Describe the standard of care in detail. Mention whether women assigned to the control arm will receive similar reimbursements and incentives as those in the intervention arm.

e/Pilot study - There is no explanation of the elements that will be assessed during the pilot stage and whether the women will also be in late pregnancy (35wks).

4/Sample size - The study is powered to detect an effect size of about 20%. Explain whether this difference would lead to meaningful impact in the state immunization program once scaled up, if efficacious.

Reviewer #2: The manuscript entitled ‘Theory-Based Immunization Health Education Intervention in Improving Child Immunization Uptake Among Antenatal Mothers Attending Federal Medical Center In

Nigeria: A Study Protocol for a Randomized Controlled Trial.

Comments

Study Design

The content in study Design (Page 9) and randomization (Page 10) is repeated.

Random selection

Page 12, the information on who prepared and provided the sampling frame list and who performed the recruitment based on the table random numbers to be stated.

Questionnaire quality control

Page 17, the statement ‘The questionnaire is first developed in English language which was later translated into Hausa language via the process of translation and adaptation of instruments figured by the World Health Organization [68]’ is repeated again in the Questionnaire Development section.

Data Analyses

Proper citation for the statistical software to be used.

Descriptive Statistics

How sure mean and sd will be employed in the study and what happened if the data are skewed.

Inferential statistics

1 or 2-tailed test for Fisher’s exact test and Independent t test to be stated. Why independent t test (assuming data are normally distributed) is used when pairwise comparison can be achieved in repeated measures.

For the statement ‘The estimated outputs that will be displayed will then be pooled into a single data set, after which the Generalized Linear Mixed Models (GLMM) analysis’ what estimated outputs and single data set refers to be clearly stated.

Repeated measures one-way analysis of variance (ANOVA) to be written as one-way repeated measures ANOVA.

The actual name for the mixed design repeated measures ANOVA from the statistical software to be used.

It is not clear how these statistical tests (one-way repeated measures ANOVA, GLMM, mixed design repeated measures ANOVA will be employed in the analysis as these tests involved repeated measures. This needs to be clearly explained.

What is the reason one-way repeated measures ANOVA is employed when two groups are involved in the study?

Also for the secondary outcomes, there are many outcomes studied. MANOVA approach could be considered e.g. repeated measures MANOVA etc provided the assumptions are fulfilled.

The subtitle normality test, descriptive statistics inferential statistics to be removed. All the information under these subtitles can be placed under Data Analyses or Statistical Analyses section.

Figure 1 requires cosmetic changes i.e arrows

Some sections in the Materials and Methods require reorganization including statistical analyses and the manuscript requires grammar check and English editing.

Reviewer #3: Great work requiring proper spelling and language check. An excellent protocol that is indeed likely to bring great improvements in an area in Nigeria where immunization if unacceptably low. It is informative and the authors are committed to sharing data on completion

Several words are repeated of misspelt

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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 #1: No

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: Review comments Theory based intervention 16th August 2021.docx

PONE-D-21-11468R1Theory-Based Immunization Health Education Intervention in Improving Child Immunization Uptake Among Antenatal Mothers Attending Federal Medical Center In Nigeria: A Study Protocol for a Randomized Controlled Trial.PLOS ONE

Dear Dr. Mohd Zulkefli,

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.

Please submit your revised manuscript by Jan 23 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Stephen R. Walsh, MDCM

Academic Editor

PLOS ONE

Journal Requirements:

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.

Additional Editor Comments (if provided):

Thank you for your resubmission. The reviewers believe that the manuscript has been improved during the revision process but there remain three points to address.

1) The fluency of the written English varies throughout the manuscript. As PLoS ONE does not have any copy-editing services, this will need to be improved before the manuscript can be considered acceptable.

2) The question of "blinding" which Reviewer 1 raised is not a question of labelling. Yes, it is clear that assignment to intervention vs control can be hidden from the study team members who evaluate the outcomes. But it appears from the description of the intervention that it is so different from the control (local standard of care), that it will be obvious to the participants which group they are in. If the participants cannot be blinded (because the intervention is obviously different from the control) then keeping the evaluating team blinded would yield a single-blind study. This could be acceptable but should be described.

3) Reviewer 1 also raised a potential confounding factor. As it appears from the description that participants in the intervention arm will be paid a lot more money than participants in the control arm, it possible that any differences in outcomes could merely be due to the financial incentives. Is there a way to pay the two groups of participants the same amount of money?

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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: Ensure the naming of supplementary documents in the text and file names are consistent throughout the manuscript.

e.g. (Refer to Supporting document 1), Refer to Supporting document 2, (Refer to supporting document 3), (Refer to Supporting document4), (Refer to Supporting document 5 and 6), Refer to Supporting document 7, (Refer to Supporting document 8), withPan African Clinical Trial Registry PACTR202006722055635(See appendix). registry PACTR202006722055635 (see appendix).

S1 Operational definitions (DOCX). S2 Sample size determination (DOCX). S3 SPIRIT check list (DOCX). S4 Questionnaire (DOCX). S5 Study pro forma (DOCX). S6 Ethical approvals (DOCX). S7 Participants consent form (DOCX). S8 Table 2: component of the intervention (DOCX).

Reviewer #3: This is an important protocol addressing a very pertinent challenge of low vaccine uptake. The author has addressed concerns indicated by the different reviewers.

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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: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Theory-Based Immunisation Health Education Intervention in Improving Child Immunisation Uptake Among Antenatal Mothers Attending Federal Medical Center In Nigeria: A Study Protocol for a Randomized Controlled Trial.

PONE-D-21-11468R2

Dear Dr. Mohd Zulkefli,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Stephen R. Walsh, MDCM

Academic Editor

PLOS ONE