Dear Dr Shankar,

Thank you for submitting your manuscript entitled "Factors influencing the participation of pregnant and lactating women in clinical trials: a mixed-methods systematic review" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff as well as by an academic editor with relevant expertise and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Ordinarily we request that you please re-submit your manuscript within two working days, i.e. by Dec 25 2023 11:59PM, but we appreciate that there may be delay due to the holiday period which we are not concerned about.

Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine

Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Pippa

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

pdodd@plos.org

Dear Dr. Shankar,

Many thanks for submitting your manuscript "Factors influencing the participation of pregnant and lactating women in clinical trials: a mixed-methods systematic review (PMEDICINE-D-23-03776R1) to PLOS Medicine. The paper has been reviewed by two subject experts and a statistician; their comments are included below and can also be accessed here: [LINK]

As you will see, the reviewers were very positive about the paper and raised nothing by way of concern but ask for clarifications and some additional considerations as constructive suggestions for improvement. After discussing the paper with the editorial team and an academic editor with relevant expertise, I’m pleased to invite you to revise the paper in response to the reviewers’ comments. We plan to send the revised paper to some of all of the original reviewers*, and of course we cannot provide any guarantees at this stage regarding publication.

When you upload your revision, please include a point-by-point response that addresses all of the reviewer and editorial points, indicating the changes made in the manuscript and either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file and a version with changes marked should as a marked-up manuscript. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper.

We ask that you submit your revision by March 7th 2024. However, if this deadline is not feasible, please contact me by email, and we can discuss a suitable alternative.

Please don’t hesitate to contact me directly with any questions (pdodd@plos.org). If you reply directly to this message, please be sure to ‘Reply All’ so your message comes directly to my inbox.

Kind regards,

Pippa

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

plosmedicine.org

pdodd@plos.org

*Please note: If your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

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Editorial comments:

1) The editorial team are in agreement with the reviewers that your manuscript was very considerately designed and reported and that it could make a valuable contribution to the field.

2) We thank you for reporting your study in accordance with PRISMA guidelines and for including the checklist as supporting information. PLOS Medicine requires that systematic reviews are updated to within 6 months of an anticipated publication date. We appreciate the complexity of your particular study but please consider this point as part of your revision.

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Comments from the reviewers:

Reviewer #1: See attachment

Michael Dewey

Reviewer #2: In this manuscript, the authors present a sweeping and comprehensive systematic review of qualitative and quantitative studies addressing the participation of pregnant and lactating women in clinical trials. This mixed methods review is very well done and contains excellent information. A few comments and questions follow.

1. The introduction is excellent and provides a sound basis for the study. This could be an introduction given to policymakers and stakeholders in its current form.

2. Page 5 first paragraph listing the exclusion on letter F-why were studies excluded if they looked at engagement in observational research? Given that the entire focus of the paper was to analyze and synthesize facilitators and barriers to engaging pregnant women in research, how is it justifiable to exclude inclusion in observational studies?

3. The findings overall were things that have been talked about for years. One of the key things that was exciting about this manuscript was the potential to put together a list of accomplishable behavior change strategies. However, the manuscript does not really do this in an effective way. Table 2 maps the findings to behavior change interventions, but still has 24 different things to accomplish. This becomes overwhelming and demotivating for investigators, participants, and governing and regulatory bodies. It would have been extremely helpful for a shorter prioritized list to be developed for change strategies that could be implemented quickly.

4. Many of the 24 different findings are somewhat related and could have been collapsed together.

Reviewer #3: I have a read the manuscript with great interest. As the authors say, their systematic review is an elaboration of a previous systematic review performed by Van der Zande et al (2018) that looked at women's reasons for participation in clinical research. Since the authors took a more comprehensive approach (a broader group of stakeholders and a broader set of studies), the result is impressive: 24 well-considered key findings.

I have a few suggestions.

A well-known problem is that studies that measure the willingness to participate are often based on retrospective data and lead to recall bias. Could data be added about the type of studies that was found?

Could data be added about the type of clinical research that was studied? As the authors acknowledge in the introduction there is a scarcity on pregnancy specific medications. Can more be said on the type of studies found? Obstetric, non-obstetric, pharmacological, non-pharmacological?

Any attachments provided with reviews can be seen via the following link:

[LINK]

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Comments from the academic editor:

I think this is a thorough and carefully conducted study and the conclusions make a lot of sense. None of the reviews indicate any major flaw and it feels like a rigorous piece of work. I agree with your decision to send it out for full review and to revise it as this point.

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General editorial requests:

1. Please upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the 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. 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 us at PLOSMedicine@plos.org.

2. Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

3. We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

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To submit your revised manuscript, please use the following link:

https://www.editorialmanager.com/pmedicine/

Your article can be found in the "Submissions Needing Revision" folder.

Attachments

Attachment

Submitted filename: shankar.pdf

Dear Dr. Shankar,

Thank you very much for re-submitting your manuscript "Factors influencing the participation of pregnant and lactating women in clinical trials: a mixed-methods systematic review" (PMEDICINE-D-23-03776R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by 2 reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

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.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Apr 17 2024 11:59PM.   

Kind regards,

Pippa

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

plosmedicine.org

pdodd@plos.org

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Requests from Editors:

GENERAL

Thank you for your very detailed and considered responses to previous comments. Please see below for further minor comments which we require you address prior to publication.

These requests pertain to specific content and formatting requirements some may have already been incorporated into the manuscript and some may not be directly relevant but please review the complete list and all that all items are included as relevant.

ABSTRACT

In the last sentence of the Abstract Methods and Findings section, please (briefly) describe the main limitation(s) of the study's methodology.

AUTHOR SUMMARY

Thank you for including an author summary which reads very nicely.

In the final bullet point of ‘What Do These Findings Mean?’, please describe the main limitations of the study in non-technical language.

We appreciated the inclusive reference to ‘lactating women and people’ in the opening bullet points but the same isn’t continued throughout. I noted your clarification regarding terminology Vs applicability to gender diverse populations (methods, line 182 onwards) which is very helpful to the reader and to me explains the aforementioned. Perhaps including a similar statement as part of the limitations (as requested above) would mitigate against any confusion regarding your use of terminology in the opening bullet points and the description of the research outcomes latterly.

INTRODUCTION

As above, please consistently refer to ‘women and people’, (or populations) line 124, for example. Please check carefully throughout the complete manuscript (including the supporting information) and revise as necessary.

TABLES

Please ensure that all tables (including those in the supporting information) are affiliated to an appropriate title and caption which clearly describes their content without the need to refer to the text.

DISCUSSION

Please present and organize the Discussion as follows: a short, clear summary of the article's findings; what the study adds to existing research and where and why the results may differ from previous research; strengths and limitations of the study; implications and next steps for research, clinical practice, and/or public policy; one-paragraph conclusion.

REFERENCES

For in-text reference callouts please place citations in square parentheses separate by commas but no additional spaces. For example, [1,3,6] or [1-3]. Please check and amend throughout all sub-sections of the manuscript and supporting files.

In the bibliography please ensure that you list up to but no more than 6 author names followed by et al.

For all web references please ensure you include an, ‘Accessed [date].’

Journal name abbreviations should be those listed in the National Center for Biotechnology Information (NCBI) databases.

SUPPORTING INFORMATION

Please ensure to cite your Supporting Information as outlined here: https://journals.plos.org/plosmedicine/s/supporting-information

In the published article, supporting information files are accessed only through a hyperlink attached to the captions. For this reason, you must list captions at the end of your manuscript file. You may include a caption within the supporting information file itself, as long as that caption is also provided in the manuscript file. Do not submit a separate caption file.

Please ensure to upload a clean (as well a tracked) version of supporting information files.

SOCIAL MEDIA

To help us extend the reach of your research, please detail any X (formerly Twitter) handles you wish to be included when we tweet this paper (including your own, your coauthors’, your institution, funder, or lab) in the manuscript submission form when you re-submit the manuscript.

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Comments from Reviewers:

Reviewer #1: The authors have answered my queries and addressed my other points.

Michael Dewey

Reviewer #3: Thanks for addressing the comments. I had asked for table 1 and table S6, we I could not find in the original resubmission. The additions in table 1 are helpful. And table S6 appears to be a typo (it should be Appendix S6). If these small comments are addressed than I have no further questions.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr Shankar, 

On behalf of my colleagues and the Academic Editor, Professor Gordon Smith, I am pleased to inform you that we have agreed to publish your manuscript "Factors influencing the participation of pregnant and lactating women in clinical trials: a mixed-methods systematic review" (PMEDICINE-D-23-03776R3) in PLOS Medicine.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. 

PRESS

We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with medicinepress@plos.org. If you have not yet opted out of the early version process, we ask that you notify us immediately of any press plans so that we may do so on your behalf.

We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine, it has been a pleasure handling your manuscript. We look forward to publishing your paper. 

Kind regards,

Pippa

Philippa Dodd, MBBS MRCP PhD  

PLOS Medicine

pdodd@plos.org