PONE-D-21-12418Effectiveness of erectogenic condom against semen exposure among women in Vietnam: Randomized controlled trial PLOS ONE

Dear Dr. Gallo,

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 manuscript has been evaluated by three reviewers, and their comments are available below. The reviewers have raised a number of concerns that need attention. They request additional information on methodological aspects of the study, interpretation of the results, as well as more information regarding the data supporting the effect of erectogenic drugs. Could you please revise the manuscript to carefully address the concerns raised?

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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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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: Yes

Reviewer #3: Yes

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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: A two-arm randomized controlled clinical trial was conducted which aimed to compare the proportion of Vietnamese couples using a novel condom to controls, as measured by the presence of PSA in vaginal fluid. The proportion of those PSA positive did not significantly differ in the two arms. The manuscript is thorough and exceptionally well written.

Minor revisions:

1- Line 181: Perhaps the word “age” has accidentally been omitted.

2- Line 193: Provide 95% confidence intervals (CI) for the proportions where PSA was detected, i.e. CIs for 6.8% and 6.7%.

Reviewer #2: The authors tried to find out whether promoting a new type of condom, recently developed for use by healthy males to improve sexual pleasure increasing penile firmness, size and erection duration, could reduce exposure of women to the semen of their partners preventing HIV and other sexually transmitted infections.

The study is well done and well presented.

Reviewer #3: This is a well-written paper with a negative finding that I believe will deserve publication, if for no other reason, than to validate the use of biochemical markers in condom studies in lieu traditional efficacy trials. However, there are a few general and specific comments I would appreciate the authors to address.

General comments

1. The claim is made that some drug added to the condom would improve different aspects of erection, but no data are provided to support these claims, and no validation was obtained from the subjects that such changes had occurred. That would be a critical element to learn. Perhaps couples were disappointed by the minor differences they experienced. Perhaps an agent that did not require extra steps in application could still affect increased utilization. The authors should elaborate more on these points.

2. Along those lines, apparently no information was collected about potential adverse side effects that could have influenced use patterns.

3. Were there any efforts to measure subject satisfaction? Discontinuation rates were low in both arms.

4. The authors noted that frequency of detectable PSA declined from baseline but did not address the impact that providing subjects with condoms could have had on that decline. This is important since the decline happened in both groups.

5. Similarly, were the subjects asked at each visit if they had adequate supplies? Could the PSA rise reflect lack of available condoms? I suspect they had been told not to use other condoms.

6. Another point that should be discussed is what percent of subjects in each arm were previously successful condom users. There are clear differences in use patterns between new users and experienced users. That is seen in all clinical trials with new condom designs. (See below).

7. Other problems that latex condom users face should also be mentioned:

a. Size problems (up to 30% of men can not fit in existing sizes). This issue gets back to point 5 – unless we know the man can use the condom, then the impact of the compound is not being reflected. This might be important to interpret results if the authors found a cohort of women who consistently tested positive.

b. Temperature problems. Latex is cold and can contribute to loss of erection during placement and discomfort for the woman.

c. Difficulty unrolling (placing) the condom. Again, the use of inexperienced couples could have masked the impact of the drug.

Were any of these problems addressed in the condoms that were used in the study? If not, perhaps they should be mentioned. Alternatively, the authors could report the outcomes of experienced condom-using couples to see if the compound did influence use or perhaps that should be the design of the next study.

Small points

Line 47-48: Could delete “in setting. . .”. Condoms are important for pregnancy protection.

Line 51: Perhaps you could add “heterosexual” to partnerships to highlight focus on this study.

Line 54: Could add the extra condom-associated problems listed above.

Line 107: What are results of the male questionnaire?

Line 122: Should probably include anticipated multiple users as an exclusionary criterion.

Line 141: Why did you not also ask about recent coitus to validate findings?

Line 189: If you had coital history, you could calculate more meaningful estimates - % of subjects who had sex and positive PSA.

Line 225 – Also underscores importance of providing condoms for free.

Line 233: Very good point.

Line 246: Please list other condom-use problems. Some of those may be solvable.

I believe this paper has great potential and look forward to reviewing any revisions the authors choose to submit.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Effectiveness of erectogenic condom against semen exposure among women in Vietnam: Randomized controlled trial

PONE-D-21-12418R1

Dear Dr. Gallo,

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,

James Mockridge

Staff Editor

PLOS ONE

Additional Editor Comments:

The manuscript has been assessed by three reviewers who find that the concerns about the methodological aspects of the study and interpretation of the results have been sufficiently addressed. Reviewer #3 suggests one minor detail in the Introduction regarding the design of the condom, which the authors may consider including in their final version for clarification

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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2. 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: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: I Don't Know

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4. 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: (No Response)

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: (No Response)

Reviewer #2: Yes

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. 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: (No Response)

Reviewer #2: Corrections, made according to useful suggestions by the reviewer 3, improved the manuscript.

I have no any additional comments.

Reviewer #3: I thank the authors for their detailed responses to my earlier comments. I think that it is always important to publish negative results, but in this case, publications particularly important because this manuscript is very thought provoking. The only suggestions I would make to the authors would be that in the introduction they describe that the compound is packed in the tip of the condom and should be retained within the inside of the condom with use, so women should generally not be exposed to the drug. This is important to understand when evaluating the reported side effects. Even if the authors do not agree to this change, I would support publication of the manuscript. I do not need to see if again before it gets accepted.

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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