Clinical practice for migraine treatment and characteristics of medical facilities and physicians treating migraine: Insights from a retrospective cohort study using a Japanese claims database

Tsubasa Takizawa; Takahiro Kitano; Kanae Togo; Reiko Yoshikawa; Masahiro Iijima

doi:10.1371/journal.pone.0315610

Peer Review History

Original SubmissionOctober 10, 2024
15 Nov 2024 Decision Letter - Sercan Ergün, Editor PONE-D-24-43022Clinical practice for migraine treatment and characteristics of medical facilities and physicians treating migraine: insights from a retrospective cohort study using a Japanese claims databasePLOS ONE Dear Dr. Kitano, 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. ============================== ACADEMIC EDITOR: The manuscript has some minor concerns to deal with. ============================== Please submit your revised manuscript by Dec 30 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. 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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: The funder, Pfizer Japan Inc., provided support in the form of salaries for authors [TK, KT, RY, and MI]. The medical writing support and data analytics support was also funded by Pfizer Japan Inc. (Tokyo, Japan). The funders had no additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. 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If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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. Additional Editor Comments : The manuscript has some minor concerns to deal with. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: Dear authors, This retrospective cohort study aimed to describe real-world clinical practices and treatment patterns in Japanese patients with migraine based on medical facilities and physicians’ specialties. Given that migraine is a major contributor to the global burden of neurological disorders, understanding the relationship between physicians' specialties and the medical environment for migraine, as well as the patterns of migraine treatment across different specialties, would help clarify where the unmet medical needs of migraine patients lie. Please find my comments for a better presentation of this study. Comment 1: Abstract: In the results section, please mention the F/M ratio and the mean age (SD) of patients. Comment 2: Introduction: This section is well-written and clearly outlines the objective of the study. However, it is better to mention the diagnostic strategy and different types of migraine. Comment 3: Results: The results section aligns with the study's aim; however, it would be beneficial to categorize patients based on migraine type, particularly in the characteristics section. How many patients experienced aura during their first presentation? Comment 4: Discussion: You mentioned that preventive treatments were more commonly used in facilities with specialists. It is important to discuss the significance of this finding and the potential side effects of relying solely on acute treatments. Without access to specialists, patients may resort to using more NSAIDs, which can lead to drug-overuse headaches and other side effects which you have mentioned but please discuss more about the importance of preventive strategy. Reviewer #2: This study provides basic information on migraine diagnosis and treatment in Japan's healthcare system by analyzing a comprehensive claims database covering more than 230,000 patients. The authors provide a balanced perspective by highlighting the study's limitations, such as missing data on migraine attack frequency and medication use frequency. Despite these limitations, this well-structured study contributes valuable guidance to advance migraine care and treatment. ****** 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: No Reviewer #2: Yes: Murat POLAT ******** [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.] 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Comments.docx https://doi.org/10.1371/journal.pone.0315610.r001
Revision 1
22 Nov 2024 Author Response Response to Editor's comments: 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 https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response: We have checked and revised the format of the manuscript according to PLOS ONE style requirements. ----------------------------------------------------------------- 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: “Medical writing support was provided by Niraj Vyas, PhD and Sonali Dalwadi, PhD, CMPP™ of MedPro Clinical Research, which was funded by Pfizer Japan Inc. The authors sincerely thank Takumi Tajima and Yoshimitsu Takamatsu from JMDC Inc. for conducting the analysis, which was also funded by Pfizer Japan Inc.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The funder, Pfizer Japan Inc., provided support in the form of salaries for authors [TK, KT, RY, and MI]. The medical writing support and data analytics support was also funded by Pfizer Japan Inc. (Tokyo, Japan). The funders had no additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response Thank you for your suggestion. We have removed funding information from the ‘Acknowledgement section’ and revised it as below: “Medical writing support was provided by Niraj Vyas, PhD and Sonali Dalwadi, PhD, CMPP™ of MedPro Clinical Research. The authors sincerely thank Takumi Tajima and Yoshimitsu Takamatsu from JMDC Inc. for conducting the analysis.” (Page 23 of the tracked version of the revised manuscript file) Funding for the medical writing support and the data analytics support is already mentioned in the current funding statement: “The funder, Pfizer Japan Inc., provided support in the form of salaries for authors [TK, KT, RY, and MI]. The medical writing support and data analytics support was also funded by Pfizer Japan Inc. (Tokyo, Japan). The funders had no additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” Therefore, we confirm that no amendment is required in the current ‘Funding statement’. We have also included theses information in the revision cover letter. ----------------------------------------------------------------- 3. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions Before we proceed with your manuscript, 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, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). 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 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 recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. Response Thank you for your suggestion. We have already added that the datasets used in this study are available to JMDC Claims Database. The access to this dataset, qualified researcher can contact JMDC Claims Database. We have now updated the ‘Data availability’ statement as below: “Restrictions apply to the availability of the data that supports the findings of this study due to contractual agreements between JMDC and hospitals. These data are available for purchase from JMDC/JMDC Claims Database (a third-party organization who owns the datasets) and qualified researchers can get access to these datasets by contacting JMDC Claims Database (website: (JP) https://www.jmdc.co.jp/jmdc-claims-database/ (ENG) https://www.jmdc.co.jp/en/jmdc-claims-database/).” (Page 23 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- 4. 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. Response We have updated the reference citation numbers throughout the manuscript and, updated the reference list. We have checked and we confirm that the revised reference list is complete and correct. ----------------------------------------------------------------- Additional Editor Comments: The manuscript has some minor concerns to deal with. [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: Yes Response Thank you for your appreciating feedback. ----------------------------------------------------------------- 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Response Thank you for your encouraging feedback. ----------------------------------------------------------------- 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 Response Thank you for your comment. We have included a revised ‘Data availability statement’ in the manuscript as below. “Restrictions apply to the availability of the data that supports the findings of this study due to contractual agreements between JMDC and hospitals. These data are available for purchase from JMDC/JMDC Claims Database (a third-party organization who owns the datasets) and qualified researchers can get access to these datasets by contacting JMDC Claims Database (website: (JP) https://www.jmdc.co.jp/jmdc-claims-database/ (ENG) https://www.jmdc.co.jp/en/jmdc-claims-database/).” (Page 23 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- 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 Response Thank you for your confirmation. ----------------------------------------------------------------- 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: Dear authors, This retrospective cohort study aimed to describe real-world clinical practices and treatment patterns in Japanese patients with migraine based on medical facilities and physicians’ specialties. Given that migraine is a major contributor to the global burden of neurological disorders, understanding the relationship between physicians' specialties and the medical environment for migraine, as well as the patterns of migraine treatment across different specialties, would help clarify where the unmet medical needs of migraine patients lie. Please find my comments for a better presentation of this study. Response Thank you for your review comments. We have provided point by point responses to all reviewers’ comments below. Comment 1: Abstract: In the results section, please mention the F/M ratio and the mean age (SD) of patients. Response We appreciate your comment. We have added female/male ratio and mentioned mean (SD) age of patients in the abstract as below: “Of 231,156 patients with migraine (mean age [SD], 38.8 [11.8] years; females, 65.3%), 81.8% had the first prescription at clinics (CPs), 42.5% underwent imaging tests, 44.4% visited general internal medicine, and 25.9% consulted neurosurgery at initial diagnosis. Imaging tests were carried out at CPs with specialists (59.4%), hospitals (HPs) with specialists (59.1%), HPs (32.9%), and CPs (26.9%) without specialists.” (Page 2 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- Comment 2: Introduction: This section is well-written and clearly outlines the objective of the study. However, it is better to mention the diagnostic strategy and different types of migraine. Response Thank you for your thoughtful comment. We have added the types of migraine and its diagnosis strategy in the ‘Introduction’ section with description as below: “Migraine is a high-ranking contributor to the global burden of neurological disorders [1]. It is characterized by a relapsing-remitting pattern of headache of variable frequencies and more common in women than men [2, 3]. There are two major types of migraine: migraine with aura and migraine without aura. The diagnosis is based on the International Classification of Headache Disorders 3rd edition according to the patient’s symptoms and characteristics [4]. Globally, migraine prevalence has been estimated to be 14–15%, and to account for 4.9% of population ill health in terms of years lived with disability [5].” (Page 3 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- Comment 3: Results: The results section aligns with the study's aim; however, it would be beneficial to categorize patients based on migraine type, particularly in the characteristics section. How many patients experienced aura during their first presentation? Response Thank you for your valuable suggestion. We agree that it is critically important to describe patient characteristics by the type of migraine. In this study, we also examined the type of migraine diagnosed at the index date (the first date of migraine treatment prescription). However, we found that the diagnosis of “migraine, unspecified” accounted for 96.6% of all migraine patients, and only 2.3% and 1.1% were with “migraine without aura,” and “migraine with aura,” respectively. Therefore, we decided to focus our study on the characteristics and treatment patterns of migraine patients, regardless of the type of migraine. We believe that investigating patients’ characteristics by the type of migraine diagnosed will be a part of future research. We have added this and revised the ‘Discussion’ section as below: “This study did not present treatment patterns for migraine stratified by severity and type of migraine. Hence, further studies that incorporate the severity of migraine as reported by patients and migraine type, and that examine the association between initial prescriptions and patients’ prognoses are necessary.” (Page 23 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- Comment 4: Discussion: You mentioned that preventive treatments were more commonly used in facilities with specialists. It is important to discuss the significance of this finding and the potential side effects of relying solely on acute treatments. Without access to specialists, patients may resort to using more NSAIDs, which can lead to drug-overuse headaches and other side effects which you have mentioned but please discuss more about the importance of preventive strategy. Response Thank you for your valuable advice. Based on the suggestion, we have revised the ‘Discussion’ section as below: “Prescription of preventive drugs was higher for specialists, especially CPs with specialists, followed by HPs with specialists. These characteristics suggest the possibility that patients with more severe migraine are seeing specialists, and that the understanding of preventive treatment is low among nonspecialists: this in turn may affect the quality of life of patients who are not prescribed preventive drugs. In addition, without access to specialists, patients may be more likely to rely on acute treatment drugs, and these patients may be at increased risk of medication-overuse headache since it has been reported that preventive medications can reduce the risk of medication-overuse headache. Therefore, there is a need to raise patients’ awareness of the importance of consulting specialists, and to strengthen medical collaboration between specialists and nonspecialists.” (Page 22 of the tracked version of the revised manuscript file) ----------------------------------------------------------------- Reviewer #2: This study provides basic information on migraine diagnosis and treatment in Japan's healthcare system by analyzing a comprehensive claims database covering more tha Attachments Attachment Submitted filename: 4. Response to Reviewers_22Nov2024.docx https://doi.org/10.1371/journal.pone.0315610.r002
28 Nov 2024 Decision Letter - Sercan Ergün, Editor Clinical practice for migraine treatment and characteristics of medical facilities and physicians treating migraine: insights from a retrospective cohort study using a Japanese claims database PONE-D-24-43022R1 Dear Dr. Kitano, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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 help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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. Kind regards, Sercan Ergün Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0315610.r003
Formally Accepted
2 Dec 2024 Acceptance Letter - Sercan Ergün, Editor PONE-D-24-43022R1 PLOS ONE Dear Dr. Kitano, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Sercan Ergün Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315610.r004

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