PONE-D-21-38415Study protocol for the BUSCopan in LABor (BUSCLAB) study: A randomized placebo-controlled trial investigating the effect of butylscopolamine bromide to prevent prolonged laborPLOS ONE

Dear Dr. Sørbye,

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Staff Editor

PLOS ONE

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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: 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: Yes

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: Yes

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: No

Reviewer #2: No

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: No

Reviewer #2: No

Reviewer #3: 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 study focus on prolonged labour and the use of buscopan.

The study aims to evaluate the duration of labour when using buscopan for prolonged labour comped to placebo.

General:

Why is it important to reduce duration of labour? Why is this the most important outcome, the primary outcome of your study?

Does the women prefer a 60 minutes reduction? Does the clinicians?

Why is the study updated as completed at clinicaltrials.gov? Have you already terminated the inclusion?

Consider using SPIRIT checklist when presenting a trial protocol – the chronology of paper could be improved by the use of spirit.

You repeat yourself several times during the paper. Please do only report eg. the objective and the outcome measures once.

Try to be more concise – current the word count is very high.

Introduction:

A definition of prolonged labour is lacking, also definition of active phase should be included in the introduction.

“Prolonged labour is common”, could you quantify?

Oxytocin- suggest that you focus on the primary adverse effect of oxytocin: uterine hyperstimaultion (tacycysystole) which may lead to compromised oxygen supply for the baby, fetal asphyxia and the need for immediate delivery. Other adverse effects could also be mentioned (postpartum hemorrhage, water intoxication, uterine rupture). The effect on breastfeeding remains as far as I am aware still unknown.

Instead of criticizing oxytocin you might consider focusing on the synergistic effect of two different drugs?

Prolonged labour – should also lead to the considerations as to whether there are other explanations as to whether labour do not progress – e.g. fetal/pelvic disproportion

Study overview:

Your hypothesis and objective should be merged into one sentence. And comnsider only to report the primary objective of the trial (like a PICO presented as a sentence)

You should report primary outcome and secondary outcomes, not ‘objectives’

Patient enrollment and eligibility criteria:

Please define the active phase for your study earlier in the text or at least mention in the introduction the variety of different definition. Do you only consider cervical dilatation to be relevant, not contractions, amniotomy, cervical length?

Please consider moving ref 26 and 27 to the introduction

No need to both text the inclusion criteria and exclusion criteria and also put the in a box. Choose one of the two options.

Sample size calculation:

Consider a brief presentation of the Dencker trial in order to help the reader, they randomised, but to which intervention?

Please consider to describe your samplesize calculation with less word, more consiese.

Is the trial GCP monitored? If yes please report that, if not please argue why not?

Reviewer #2: The manuscript needs a language editor. There are so many typographical errors.

ABSTRACT

The objectives of the study is not well defined.

The authors stated: Women are

included in the first stage of labor if they cross the partograph alert line with a cervical

dilation between 3–9 cm. Does it mean that authors recruit patients at 9cm cervical dilatation? If yes, would that not be too late?

INTRODUCTION

The authors stated: Another class of drugs, antispasmodics, has been used to prevent poor progress of labor in both

developing and developed countries. The authors should replace developed to 'high-income' and replace developing to 'low and middle-income'

Reviewer #3: Comments to the Author

I read with great interest the enclosed Manuscript which falls within the aim of Plos One.

In my honest opinion, the topic is interesting enough to attract the readers’ attention. Methodology is accurate.

However, it is necessary to cite and discuss previous trials and meta-analyses regarding the aim of trial, since there are several trials on the issue. See and cite this updated meta-analysis which summarizes the available evidence from RCTs, PMID: 32629224.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Study protocol for the BUSCopan in LABor (BUSCLAB) study: A randomized placebo-controlled trial investigating the effect of butylscopolamine bromide to prevent prolonged labor

PONE-D-21-38415R1

Dear Dr. Sørbye,

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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Kind regards,

Hanna Landenmark

Staff 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 #1: Yes

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 #1: Yes

Reviewer #2: Partly

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 #1: Yes

Reviewer #2: No

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 #1: No

Reviewer #2: No

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 #1: Yes

Reviewer #2: No

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 #1: Congratulation, a interesting RCT is coming up. The paper has been improved and I find it ready for publication,

Reviewer #2: The authors did not address all the issues previously raised. If they addressed it, the authors must outline/highlight it in yellow. They need to be detailed on their specific revision

Reviewer #3: Thank you for giving me the opportunity of reviewing the revised version of the enclosed manuscript. All the issues highlighted in the previous version were solved by the authors. No further concerns.

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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: Yes: George

Reviewer #3: No

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