PONE-D-20-25593

The safety and efficacy of doxazosin in medical expulsion therapy for distal ureteral calculi: a meta-analysis

PLOS ONE

Dear Dr. Wang,

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.   The unedited reviewers comments are below

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We look forward to receiving your revised manuscript.

Kind regards,

Adrian Stuart Wagg, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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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4. 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

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewers report: the safety and efficacy of doxazosin in medical expulsion therapy for distal ureteral calculi: a meta analysis

The objective of the study was the evaluation of the safety and efficacy of doxazosin relative to placebo or temp solution in medical expulsion therapy for distal ureteral calculi.

Abstract: This is an accurate summary of the following study

introduction: There are some minor grammatical alterations needed in the introduction but these are editorial and do not necessarily need alterations by the authors.

The size of stones should be specified do the authors mean 10 millimeters in diameter or length for example?

The last sentence of the background can be deleted this study does not assess an hypothesis but merely analyzes the results of previously tested hypotheses

Literature search:

I think it would be worthwhile changing the flow of the sections here. the inclusion and exclusion criteria should perhaps precede the literature search. Were there any language restrictions placed on the searches?

Study selection: although not required by the PRISMA reporting system could the authors tell us how many articles required discussion following discrepancy after independent review?

I assume that patient sex rather than gender was extracted?

Did the authors use a standard method to assess the quality of the study which was the basis of information in figure two?

The statistical analysis is appropriate to the methodology

results: In the sentence following the notes on table one the letters DP&T are incorrectly ordered in terms of explaining the definitions

I think the correct description is ureteric rather than ureteral stones. this needs correcting throughout

The unit of expulsion time is missing, I assume this is hours but this needs stating

Could the authors give the proportions of exposed patients who experienced each of the listed adverse events?

Are there data for comparative rates of adverse events between doxazosin and tamsulosin?

Discussion: The sentence following the paragraph “we found differences in the risk of common adverse reactions…” appears to be redundant . Were the authors able to ascertain whether any medical intervention was required for drug associated adverse events?

Where the authors use the term eviction time, I think they mean expulsion time

The authors rightly note that they were unable to include unpublished study data . Did they perhaps investigate whether there were such data ? For example, a search of a clinical trials registry might have uncovered other studies of relevance for which there were no results. In terms of limitations, were included studies English language only? This needs clarification

If the authors used the meta analytical results to conduct a power and sample size calculation , what number of patients that would be required for a fully powered study? They conclude that more high quality tests with larger samples might be needed but this may not be the case

Reviewer #2: Thank you for asking me to review this meta-analysis of doxazocin for the treatment of ureteric stones.

Overall this is a valid subject and the meta analysis is conducted well. The inclusion and exclusion criteria for the papers are well described and the statistical methods seem appropriate.

I do have a few comments that should be addressed.

The word "ureteral" is used throughout. Would "ureteric" be a better choice?

Abstract:

There is an inconsistency regarding the episodes of pain between groups, with the doxazocin group experiencing "more episodes of pain" (results, line 7) and "fewer pain episodes" (conclusion). This should be corrected.

Background:

"There are long waiting times for observation and MET". This sentence seems counterintuitive - are the authors suggesting that these treatments take a long time to work, or that there are long wait times to commence treatment, which would be the usual interpretation of this wording. This should be clarified.

Data extraction and assessment of methodological quality

"Patient genders" refers to biological sex, not gender. This should be corrected.

Discussion

The claim that 1 to 2% of hospital admissions are due to ureteral stones should be referenced or removed.

"70% of ureteral stones develop within the lower part of the ureter". Is this correct? surely stones form in the kidney and then move to the ureter? Either way it needs referencing.

The discussion section is overly long and repeats much of the method and background. It should be heavily edited or rewritten to focus on discussion the findings of the work, rather than reahashing previous sections.

Limitations; the limitation of the study not reporting their SD is a limitation of the statistical method, not of the software. The sentence referring to "Review Manager" should be edited.

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PONE-D-20-25593R1

The safety and efficacy of doxazosin in medical expulsion therapy for distal ureteric calculi: a meta-analysis

PLOS ONE

Dear Dr. Wang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit and there are only some minor considerations suggested by the reviewers, these are below. 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 29 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

We look forward to receiving your revised manuscript.

Kind regards,

Adrian Stuart Wagg, MD

Academic Editor

PLOS ONE

Reviewer #1: Some minor comments

Thank you for asking me to review a revised version of this paper. I have reviewed the previous comments In response to which the authors have made considerable revision to their paper.

My comments on the revised version are as follows:

In the final sentence of the introductory section, the authors might replace the words “which may find “ with “and hypothesized that “

In the second line of the study selection section, the word randomized is repeated In the same sentence. Perhaps the authors might replace the 1st “randomized" with either recruited or enrolled ?

In the literature search section, the authors should state that there were no language limitations on their search or retrieval

In the expulsion time section the authors omit the units of time measured in their text

In the pain episodes section, perhaps “compared with placebo treatment, doxazosin treatment led to a statistically significant reduction in pain episodes”?

In the drug adverse reaction in section, in the text the authors should specify the comparator where they quote the odds ratio

In the expulsion time section when comparing doxazosin to tamsulosin, the authors repeat doxazsin in each group and the unit of time is missing

Reviewer #2: Thank you for the opportunity to review this revised manuscript. I note that the comments of myself and my co-reviewer have been addressed in full.

I have three minor points to consider.

Methods: Analysis. "When the I2 value suggested very low heterogenicity" - the cut off for "very low" is not given and should be added.

Discussion: "The mechanism of action of alpha-adrenergic blockers [23] involves the relaxation of the distal ureter by decreasing smooth muscle tension instead of eliminating its activity" this sentence is unclear and should be reworded. The following sentence "In 2005, Sigala et al. [22] determined that the distal ureter expresses higher levels of α1-adrenoceptor mRNA than the proximal and medial ureters." doesn't really add much and could be removed.

In the conclusions you state "We concluded that doxazosin has potential as a MET for ureteric stones." It seems that your work demonstrates more than this, and the conclusion could be firmer.

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The safety and efficacy of doxazosin in medical expulsion therapy for distal ureteric calculi: a meta-analysis

PONE-D-20-25593R2

Dear Dr. Wang,

We’re pleased to inform you that your manuscript is now suitable for publication following academic editor review of the minor amendments and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Adrian Stuart Wagg, MD

Academic Editor

PLOS ONE