Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: A prospective cohort study

Charlotte M. Page; Saduma Ibrahim; Lawrence P. Park; Megan J. Huchko

doi:10.1371/journal.pone.0222750

Peer Review History

Original SubmissionJune 26, 2019
1 Aug 2019 Decision Letter - Violet Naanyu, Editor PONE-D-19-17741 Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study PLOS ONE Dear Dr. Page, 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. We would appreciate receiving your revised manuscript by Sep 15 2019 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable 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. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. 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. We look forward to receiving your revised manuscript. Kind regards, Violet Naanyu Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. In your Methods section, please provide additional information about the participant recruitment method, including a statement as to whether your sample can be considered representative of a larger population, and a description of how participants were recruited. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] 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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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 ****** 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 ****** 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: Line 102- Women with cervical lesions not amenable to cryotherapy or 103 suspicious for cancer were referred to a gynecologist. What was the distance women had to travel to see a gynecologist and what was the waiting time? Line 112- The study population for the main trial were women in Migori County who were eligible 113 for cervical cancer screening based on the Kenya Ministry of Health’s guidelines: 25-65 years old with an intact uterus and cervix. – add reference Reviewer #2: Reviewer Comments “Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study” General comment • The manuscript is well written however there are some comments in each of the section that could improve the manuscript. Abstract • In the results section provide direction of association for the significant variables whether positive or negative Introduction More background need to be provided on the linkage rate after screening in the region and in the whole country in general. This is not clear before assessing factors what is the burden. Methodology Were the participants counseled prior or after testing? In the methods it is stated that this current manuscript focuses on the group that was exposed to enhanced linkage strategy that included transport facilitation for a limited number of participants. How many among the one studied had facilitated transportation? How was this handled in the analysis. Results • The variable Missed work to come to the CHC for screening was this for women who were employed or for all women • How were the variables “Told by partner, family member, or someone else important to come to the CHC” and “Told by partner, family member, or someone else important not to come to the CHC” phrased since one is the negative of the other. • “Women with a college education or beyond were not significantly more likely to present for treatment than women in the least educated category (OR 2.17, 95% CI 0.65-7.26), with a wide confidence interval in the setting of very few women having a college education or more”. Why not consider collapsing the groups? • Was multicollinearity before the adjusted odds ratio were obtained. Data Availability Indicated that the data is available but no link to the data ****** 6. 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: Yes: Elkanah Omenge Orang'o Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (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. Registration is free. 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 figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0222750.r001
Revision 1
9 Aug 2019 Author Response Response: We thank the editor and reviewers for your careful reading of our manuscript and for your thoughtful comments. We have incorporated your suggestions into the updated version of our manuscript as detailed below. Please note that line numbers in our responses below refer to the tracked version of the revised manuscript. Responses to comments from the editor: 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf andhttp://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response: We have reviewed PLOS ONE’s style requirements to ensure that our manuscript is compliant. We made changes in the punctuation around the in-text citations. 2. In your Methods section, please provide additional information about the participant recruitment method, including a statement as to whether your sample can be considered representative of a larger population, and a description of how participants were recruited. Response: Thank you for this suggestion. We have added the requested information to the Methods section (lines 103-8). 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Response: There are no ethical restrictions to sharing a de-identified dataset. We now include this dataset as Supporting Information file “S2 Dataset.” Responses to comments from the reviewers: Reviewer #1: Line 102- Women with cervical lesions not amenable to cryotherapy or 103 suspicious for cancer were referred to a gynecologist. What was the distance women had to travel to see a gynecologist and what was the waiting time? Response: These are excellent questions. Women were referred to a gynecologist at Migori County Referral Hospital, which is in the capital of Migori County. We have added this information to our Methods section (lines 122-3). The geodetic distance to this site from the homes of women in the study population ranges from 4 to 40 km, with a median of 29 km. We do not have information on the waiting time; however, the supervising gynecologist was a consultant on the study and worked to facilitate care for all referred women in a timely fashion. Line 112- The study population for the main trial were women in Migori County who were eligible 113 for cervical cancer screening based on the Kenya Ministry of Health’s guidelines: 25-65 years old with an intact uterus and cervix. – add reference Response: We have added a reference and removed the statement about “an intact uterus and cervix” after clarifying against the reference (lines 136-7). Reviewer #2: Reviewer Comments “Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study” General comment • The manuscript is well written however there are some comments in each of the section that could improve the manuscript. Abstract • In the results section provide direction of association for the significant variables whether positive or negative Response: This is a good suggestion. We have updated the abstract accordingly (lines 39-42). Introduction More background need to be provided on the linkage rate after screening in the region and in the whole country in general. This is not clear before assessing factors what is the burden. Response: Since this is the first protocol in Kenya to incorporate hrHPV testing as part of screening through government health facilities, there is no linkage to treatment rate to which to compare outside of this study. However, in Phase 1 of this study, which employed standard linkage to treatment, less than 50% of women were successfully linked. We have included this data in the Methods section (lines 89-90). Methodology Were the participants counseled prior or after testing? Response: The participants were counseled prior to testing. We have provided clarification about this counseling in lines 108-9. In the methods it is stated that this current manuscript focuses on the group that was exposed to enhanced linkage strategy that included transport facilitation for a limited number of participants. How many among the one studied had facilitated transportation? How was this handled in the analysis. Response: We clarified with the study coordinator, and there actually was no transport facilitation for women in Phase 2 of the study, which is the phase of interest for this research. We apologize for this error and have removed this statement from the manuscript (line 94). Results • The variable Missed work to come to the CHC for screening was this for women who were employed or for all women Response: This variable applied to all women. We think there is something about the decision and ability to miss work that separates women who missed work from those who either work inside the home or work outside the home and didn’t miss work. In preparing our response to this question, we realized that the frequencies in Table 1 for this variable were incorrect; they are now accurate. • How were the variables “Told by partner, family member, or someone else important to come to the CHC” and “Told by partner, family member, or someone else important not to come to the CHC” phrased since one is the negative of the other. Response: The questions were worded to participants at the CHCs as follows: “Did your partner, family member, or anyone else important to you tell you to come?” and “Did your partner, family member, or anyone else important to you tell you not to come?” During training and piloting of the surveys, we had the research assistants stress the difference between the two questions. • “Women with a college education or beyond were not significantly more likely to present for treatment than women in the least educated category (OR 2.17, 95% CI 0.65-7.26), with a wide confidence interval in the setting of very few women having a college education or more”. Why not consider collapsing the groups? Response: It would certainly be reasonable to combine the groups “at least some secondary” and “college or beyond”; however, we chose to keep them separate to provide more detailed data on the distribution of education levels in the study population. • Was multicollinearity before the adjusted odds ratio were obtained. Response: Yes, we did test for multicollinearity among the variables that we used in the multivariable logistic regression models. The variance inflation factor (VIN) for all variables was <2, indicating that collinearity is not a concern. Data Availability Indicated that the data is available but no link to the data Response: We now attach the de-identified data as a Supporting Information file. Attachments Attachment Submitted filename: CP Kenya PLOS ONE response to reviewers.docx https://doi.org/10.1371/journal.pone.0222750.r002
22 Aug 2019 Decision Letter - Violet Naanyu, Editor PONE-D-19-17741R1 Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study PLOS ONE Dear Charlotte M Page, 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 minor points raised during the second review process. We would appreciate receiving your revised manuscript by August 30, 2019. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable 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. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. 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. We look forward to receiving your revised manuscript. Kind regards, Violet Naanyu Academic Editor PLOS ONE Additional Editor Comments (if provided): Dear Authors, Thank you for a thorough review and editing of the manuscript. The reader gets a full picture of the study activities, associated analyses, and conclusions reached. [Note: HTML markup is below. Please do not edit.] 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: (No Response) ******** 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: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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: Yes Reviewer #2: 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: Yes ****** 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: This is a well written paper with interesting findings that may inform similar settings in as far as cervical cancer screening and treatment is concerned. Reviewer #2: (No Response) ****** 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: Yes: Orang'o Elkanah Omenge Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (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. Registration is free. 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 figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Reviewer_comments_1.docx https://doi.org/10.1371/journal.pone.0222750.r003
Revision 2
28 Aug 2019 Author Response Manuscript: PONE-D-19-17741 Response: We thank the editor and reviewers for your careful reading of our manuscript and for your thoughtful comments. We have incorporated your suggestions into the updated version of our manuscript as detailed below. Please note that line numbers in our responses below refer to the tracked version of the revised manuscript. Responses to comments from Reviewer 2: 1. The variable Missed work to come to the CHC for screening was this for women who were employed or for all women Response: This variable applied to all women. We think there is something about the decision and ability to miss work that separates women who missed work from those who either work inside the home or work outside the home and didn’t miss work. In preparing our response to this question, we realized that the frequencies in Table 1 for this variable were incorrect; they are now accurate. Comment: How many among those working outside home missed work to come to CCC. Since the ones at home might not have considered themselves to have missed work. This all depends on how the questions was phrased and from the frequencies the number missing work is lower than the number working outside home. Response: The questions were phrased as, “Are you currently working outside of the home?” and “Did you have to miss work to come to this campaign?” Six percent of women who do not work outside the home reported missing work to come to the CHC, and 57% of women who work outside the home reported doing so. We have added this data to the text of the manuscript (lines 177-9). The 2x2 table is below. Missed work Did NOT miss work Work outside the home 165 126 Do NOT work outside the home 12 202 When the analysis was limited to the 291 women who work outside the home, the association between missing work to come to the CHC and presenting for treatment remained significantly significant (2.01, 95% confidence interval 1.26-3.22). 2. “Women with a college education or beyond were not significantly more likely to present for treatment than women in the least educated category (OR 2.17, 95% CI 0.65-7.26), with a wide confidence interval in the setting of very few women having a college education or more”. Why not consider collapsing the groups? Response: It would certainly be reasonable to combine the groups “at least some secondary” and “college or beyond”; however, we chose to keep them separate to provide more detailed data on the distribution of education levels in the study population. Comment: Due to the small numbers in the College group why not combine them with the secondary to gain more power. Then we can be able to make the conclusion that education is a factor currently its only between secondary and primary. Response: We have combined the college group with the secondary education group and updated the statistical analysis to reflect this change. Attachments Attachment Submitted filename: CP Kenya PLOS ONE response to reviewers v.2.docx https://doi.org/10.1371/journal.pone.0222750.r004
9 Sep 2019 Decision Letter - Violet Naanyu, Editor Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study PONE-D-19-17741R2 Dear Charlotte Page, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. With kind regards, Violet Naanyu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0222750.r005
Formally Accepted
11 Sep 2019 Acceptance Letter - Violet Naanyu, Editor PONE-D-19-17741R2 Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: a prospective cohort study Dear Dr. Page: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Violet Naanyu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0222750.r006

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