PONE-D-23-23499Investigating opportunities for surveillance of long term chlamydia complications in the Netherlands: a qualitative studyPLOS ONE

Dear Dr. den Boogert,

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: N/A

Reviewer #2: N/A

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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: No

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: 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: General comments:

Thank you for the opportunity to review this interesting manuscript on opportunities for surveillance of long term chlamydia complications in the Netherlands. The manuscript presents findings of a qualitative study among 15 healthcare professionals to explore their views on potential future routine surveillance of chlamydia related long-term complications, including pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI).

Given current debates on a paradigm shift from Chlamydia infection control to disease control, I believe that this is a timely topic of great public health relevance and general interest to PLOS ONE readers. However, I think that for the more general reader, it would be good if the authors could add further information to the introduction/discussion sections, including regarding limitations on the use of complications surveillance to compensate for reduced screening of asymptomatic infections. It is also important to acknowledge methodological limitations and ensure that relevant guidance on reporting of qualitative studies has been followed.

Specific comments:

1. Objectives in abstract and introduction:

I wonder whether the objectives could be stated a bit more clearly (possibly seeking support from a native speaker for this – well aware that I am not a native speaker, myself). I am not sure, for example, whether the word ‘opportunity’ is the best word to capture/specify what the authors mean – were you thinking of the word more in the sense of possibility/ options or in the sense of a favourable chance or circumstance and prospect for success? In the abstract, the objective ends with ‘aiming to evaluate the impact of changing chlamydia testing strategies on occurrence of complications.’ I think this refers to the routine surveillance of complications (i.e. complications surveillance could be used to evaluate the impact of potential future changes in testing strategies), but the quick reader might think that your qualitative study aims to evaluate to impact of changing testing strategies…

2. Introduction/ Discussion:

a. You could consider briefly mentioning the prevalence and trends of Chlamydia complications globally and/or nationally (e.g. possibly He et al 2023 for the global burden of PID and EP, doi: 10.1186/s12889-023-16663-y)

b. The general reader might be interested to know whether any other countries have already changed testing strategies and/or have already some form of Chlamydia complications surveillance in place and what their experiences is with this?

c. You could consider discussing surveillance of Chlamydia complications with regards to certain limitations, including relating to the correlation of Chlamydia infections with PID and with subsequent EP and/or TFI. For example, trends could be discordant due to changes in the health care system other than STI testing, e.g. regarding delayed or inadequate treatment of Chlamydia infection and/or PID. (For changes in access to hospital care, see for example the paper by Chen et al 2005 doi: 10.1136/sti.2004.012807 ). In the case of TFI, possibly changing pregnancy rates would also need to be considered when analysing data.

d. It would also be good if the more general reader could have an idea on how likely it is that it can be differentiated that PID, EP and/or TFI are due to Chlamydia, and not due to other infections, such as Gonorrhoea (also keeping gonorrhoea-related antimicrobial drug resistance in mind), or bacterial vaginosis-associated bacteria, or other causes, such as endometrioses (keeping changing trends in endometriosis rates in mind)? Having said all this, I believe that PID, EP and TFI changes are worth monitoring, regardless of its cause, but issues around cost-effectiveness might need to be discussed.

e. Line 264-265 reads “Based on what respondents told us, we feel that gynaecologists, more than GPs, actually diagnose the complications, and properly register them in their hospital databases”. International readers might not be sure why gynaecologists would be able to register complications in ‘their hospital database’, as they might not know whether in the Netherlands gynaecologists are usually based at hospitals (including for outpatient care) or in (private or public) clinics/ practices separate from hospitals. It would therefore be good to briefly provide in the introduction or discussion some background information on the Dutch health care system, also in terms of access to free health care.

f. Generally, I think the manuscript is well written, I have only spotted several typos/ grammar/spelling errors, and it is necessary to cross-check the whole document, e.g. in line 135, 143,147 and 256 etc need to say “patient’s” or “patients’” instead of “patients”, line 113 reads “in-dept interviews” instead of “in-depth interviews”, line 188 should say “tubal pathology” instead of “tuba pathology”, and in line 165 please clarify what is meant by “red.” In “red. perform an STI test…”. In line 83, please indicate the meaning of the acronym SHC at first use, even if most readers will guess what is meant. In line 240 it is not clear what ‘NIVEL’ means.

3. Methods:

a. Following reporting guidance: Guidance by different journals varies, but I think it would be good if you could indicate at the beginning of the methods section that you have used relevant international guidelines/checklists for the reporting of qualitative research. Therefore, if the editor agrees, please upload with your rebuttal letter a SRQR checklist(http://journals.lww.com/academicmedicine/fulltext/2014/09000/Standards_for_Reporting_Qualitative_Research___A.21.aspx) or the COREQ checklist (https://academic.oup.com/intqhc/article/19/6/349/1791966/Consolidated-criteria-for-reporting-qualitative), indicating the page/line numbers of your manuscript where the relevant information can be found, updating the manuscript as needed to ensure all reporting requirements are met.

For example, I noted that there is insufficient information on your qualitative approach/ research paradigm and researcher characteristics and reflexivity.

b. Sample size and saturation: Line 85 indicates that the sample size was determined by the principle of saturation and that where saturation was not reached or was difficult, medical doctors working under supervision of a gynaecologist were recruited. Overall, I think that the sample sizes for the different specialities in different regions of the country are rather low and it seems unlikely that saturation (however defined) has been reached for all relevant concepts (although it might have been met for some of the most important themes, but this would need to be more clearly stated). Generally, it seemed that the reported results are quite descriptive and do not go much into depths. Nevertheless, I think you have retrieved important information from this research, it may only need further information and better acknowledgement of its limitations. For example, you found that one of the six GPs said they sometimes diagnose and treat PID without referral to a gynaecologist, which would mean that the diagnosis would not be captured by gynaecologists/ in a hospital database. It is unclear whether in a bigger sample, more GPs would have reported similar behaviour.

The concept of ‘data saturation’ is well-debated in qualitative methodology literature and it would therefore be good if you could define this term more clearly and your decisions around it in your paper. Did you have an initial sample size you were aiming for? How did you decide (before and/or during data collection) your definition of data saturation to conclude recruitment, and how did you measure this? How could you be sure there were no more relevant themes to come, or that further interviews could not contribute to refining of the themes? Please see for example the references below regarding the current debate on ‘saturation’ and sample sizes in qualitative research:

� Saunders B, et al. Saturation in qualitative research: exploring its conceptualization and operationalization. Qual Quant. 2018;52(4):1893-1907. Epub 2017 Sep 14. DOI: 10.1007/s11135-017-0574-8

� Tight, M. (2023). Saturation: An Overworked and Misunderstood Concept? Qualitative Inquiry, 0(0). https://doi.org/10.1177/10778004231183948

� Malterud K, et al: Sample Size in Qualitative Interview Studies: Guided by Information Power. Qual Health Res 2016, 26(13):1753-1760. DOI: 10.1177/1049732315617444

Reviewer #2: Thank you for the opportunity to review this manuscript which uses qualitative methods to examine clinician practices and behaviors related to diagnosis and reporting of potential complications of chlamydia infection including PID, EP, and TFI. The manuscript could benefit from a reframe as I had to read through a couple of times to piece together the information. Also somewhat related, better description of the current guidelines and health record systems in Netherlands would really help orient the non-Netherlands based reader.

Detailed suggestions/comments are listed below:

1. Abstract – the aims seem to be a bit misaligned with results/conclusion. Based on the results and discussion it seems that the purpose of the study is to use key informant interviews to understand ways to enhance a potential surveillance system for chlamydia complications. However, the objective seems to suggest a study that examines the impact of changes in chlamydia testing strategies. Please clarify.

2. Introduction –

a. The introduction would benefit from a more complete presentation of the debate around ‘test and treat’ for chlamydia. As it stands, the authors seem to suggest minimal benefit to chlamydia screening, whereas the literature suggests otherwise. In fact, the limitations in the literature are more specifically related to which screening strategies and intervals to use, which age to start and stop screening, and whether screening males is necessary.

b. Adding a brief overview of the current chlamydia testing guidelines and surveillance systems in the Netherlands would lend context to your study especially for readers outside of the Netherlands.

c. It seems the research question is whether there is a precedent or existing infrastructure that can be used to conduct surveillance for PID, EP, and TFI, the need for which may arise if widespread chlamydia screening was eliminated. If I’m correct, then perhaps inclusion of information on surveillance (in other settings) for PID/EP/TFI would be useful.

d. Paragraph on aims – as written this is unclear. Please rephrase.

3. Methods –

a. Sampling – could you clarify what you mean by stakeholders analysis. Do you mean a qualitative analysis?

b. Who conducted the interviews and were they all conducted by the same person?

4. Results/Discussion –

a. What is the added value of inclusion of the emergent themes related to diagnosis? Most of what is here is well established in the literature (e.g., difficulty in diagnosing PID).

b. Can you describe the standard practice/guidelines for registration of cases. What does registration mean? Presumably there currently is no surveillance system, but this is referring to medical record procedures and coding? Please clarify.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-23499R1Investigating possibilities for surveillance of long term chlamydia complications in the Netherlands: a qualitative studyPLOS ONE

Dear Dr. den Boogert,

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 address Reviewer 1's comments regarding additional description of your methods for qualitative analysis and sample size, and inclusion of the SRQR checklist. Please also complete a final check of the manuscript for grammar and spelling prior to resubmission.==============================

Please submit your revised manuscript by May 23 2024 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,

Jesse L Clark, MD, MSc

Academic Editor

PLOS ONE

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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.

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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: (No Response)

Reviewer #2: All comments have been addressed

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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

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

Reviewer #1: (No Response)

Reviewer #2: N/A

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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: (No Response)

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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

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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: Thank you for responding to the reviewer questions. I think the manuscript has significantly improved and may be published after the points below have been addressed:

Methods section

1. Line 121 – Thank you for adding the below in response to my previous comment regarding which qualitative approach/research paradigm you have used: “An interpretive qualitative research approach was used for data collection by developing a semi-structured interview guide…”. Would you mind elaborating on this approach and providing a reference for this? Also, you have added this to the ‘data collection’ section, but since a research paradigm usually does not only relate to data collection, but also to data analysis and interpretation, it would be good if you could elaborate how your overall research paradigm influenced also data analysis and interpretation.

2. The authors have indicated that they have checked the “manuscript according to the SRQR checklist and added the checklist to this letter (A Word file named SRQR Checklist)” – However, the checklist has not been included in the pdf file and I have not been able to find the SRQR checklist elsewhere in the system for some reason…

Discussion

3. Line 287 – First, thank you for partly addressing my previous question regarding sample size and saturation by making changes to the methods section and the discussion. This is now clearer, apart from line 287, where you say “Saturation for SHC doctors was reached after two interviews, a third interview was conducted to confirm saturation.” Instinctively, the reader might think that after only two interviews, there might still be a high chance of missing important themes or perspectives – although in a highly homogenous sample, such as SHC doctors, this might be less of an issue, if referring only to ‘main themes’, as you had done for GPs; there might also be sampling bias for the first few participants, especially if a ‘network/ snowball sampling’ approach has been used. I would therefore be careful with such statements, or justify them better with reference to the literature (including the literature I had referred to during my previous review).

Entire manuscript

4. I have spotted a number of grammar mistakes – for example:

- Abstract, line 33 – Instead of “the possibility to introducing” it should say “the possibility of introducing”

- Introduction, line 91 – Instead of “monitor trends in chlamydia.” it should say something like “monitor trends in chlamydia infections.”

- Line 96 – Instead of “More specific,, we aimed to understand...” it should read “More c, we aimed to understand…”

After the revision, the entire manuscript will therefore need to be cross-checked for typos/ grammar mistakes.

Reviewer #2: The reviewers have addressed all comments raised as part of the original review. I have just a few minor comments:

Line 81 - there is a word missing in this sentence

Line 84 - missing punctuation

Line 217-219 - this sentence is unclear; CAT should be defined on first use

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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

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Investigating possibilities for surveillance of long term chlamydia complications in the Netherlands: a qualitative study

PONE-D-23-23499R2

Dear Dr. den Boogert,

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.

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Kind regards,

Jesse L Clark, MD, MSc

Academic Editor

PLOS ONE