Understanding the combined symptom medication score in the light of contexts and mechanisms

Anne Møller Lohmann; Anne Poder Petersen; Johannes Martin Schmid; Hans Jürgen Hoffmann; Jeanette Finderup

doi:10.1371/journal.pone.0326143

Peer Review History

Original SubmissionDecember 11, 2024
11 Dec 2024 Author Response https://doi.org/10.1371/journal.pone.0326143.r001
Decision Letter - Davor Plavec, Editor Dear Dr. Lohmann, 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: please make the corrections according to reviewer's comments or write a detailed rebuttal on a point by point basis. ============================== Please submit your revised manuscript by Mar 28 2025 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. 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, Davor Plavec, MD, MSc, PhD, Prof. 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 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 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The ILIT.NU trial, including this realist evaluation, is financed by Innovation Fund Denmark, Aarhus University, and Aarhus University Hospital.” 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 author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. In the online submission form, you indicated that [The data that support the findings of this study are available on request from the sponsor, Hans Jürgen Hoffmann. The data are not publicly available due to privacy or ethical restrictions.]. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Additional Editor Comments: Dear Authors, please make the corrections according to reviewer's comments or write a detailed rebuttal on a point by point basis. [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? 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 Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: Comments The method of processing information and monitoring the outcome of treatment through questionnaires in patients with chronic disease is an established method, but your review and analysis are important because of the connection of all the information you have collected. Reviewer #2: Dear Author, This paper presents a very interesting perspective on CSMS and the validity of the questionnaire. Could you clarify how you decided on the five preliminary themes? This is not clearly explained in the methods section. The results section could be written in a more concise manner. Tables 1 and 4 are somewhat repetitive. Additionally, the refinement of the CMO should be described in the methods section. There are many descriptive statistics that could be presented in a table format. In the discussion section, it would be helpful to include a comparison with similar research to better understand the impact of these CMOs on the final study results. Overall, I believe this paper could be written in a more engaging way. ****** 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 ******** [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. https://doi.org/10.1371/journal.pone.0326143.r002
Revision 1
3 Apr 2025 Author Response Journal 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 Answer: We have thoroughly reviewed the templates to confirm that everything adheres to PLOS ONE’s style requirements. 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The ILIT.NU trial, including this realist evaluation, is financed by Innovation Fund Denmark, Aarhus University, and Aarhus University Hospital.” 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 author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Answer: Thank you for bringing it to our attention. We have now deleted the Acknowledgement section and updated the Funding Statement. The data used for this realist evaluation were collected as part of the ILIT.NU trial. The ILIT.NU trial received funding from Innovation Fund Denmark, Aarhus University and Aarhus University Hospital. However, this specific realist evaluation did not receive any funding. 3. In the online submission form, you indicated that [The data that support the findings of this study are available on request from the sponsor, Hans Jürgen Hoffmann. The data are not publicly available due to privacy or ethical restrictions.]. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Answer: The data supporting the findings of this study contain potentially sensitive information, including health-related data and personally identifiable comments from free text boxes that cannot be fully anonymized. As a result, data sharing is subject to ethical and legal restrictions. The authors do not have sole authority over data access decisions. Our ethical approval requires that data sharing complies with the European Parliament and Council Regulation No. 2016/679 of 27 April 2016 (General Data Protection Regulation, GDPR). Making the data publicly available would conflict with GDPR requirements, which mandate the protection of personal and sensitive information. Therefore, data access is restricted in accordance with these regulations and the guidelines set by The Scientific Ethical Committees for Region Midtjylland, which has imposed these restrictions to protect participant confidentiality. Requests for access to the data can be submitted to: The Scientific Ethical Committees for Region Midtjylland Skottenborg 26 DK-8800 Viborg Tel: +45 7841 0183 Email: komite@rm.dk Website: www.komite.rm.dk Reviewer #1: The method of processing information and monitoring the outcome of treatment through questionnaires in patients with chronic disease is an established method, but your review and analysis are important because of the connection of all the information you have collected. Answer: Thank you for your positive feedback and for recognizing the significance of this approach. While questionnaire-based outcome monitoring is well established, we appreciate your recognition of our study’s value in integrating qualitative data to provide a comprehensive perspective on the Combined Symptoms Medication Score. Reviewer #2: Dear Author, This paper presents a very interesting perspective on CSMS and the validity of the questionnaire. Answer: Thank you. Could you clarify how you decided on the five preliminary themes? This is not clearly explained in the methods section. Answer: The five preliminary themes was developed using an inductive approach. This has been elaborated in the methods section to ensure greater transparency. The results section could be written in a more concise manner. Tables 1 and 4 are somewhat repetitive. Additionally, the refinement of the CMO should be described in the methods section. There are many descriptive statistics that could be presented in a table format. Answer: We have revised the results section to make it more concise and precise. Additionally, we have moved Table 4 up before Table 3 and incorporated the descriptive statistics into the former Table 4 (now Table 3), removing them from the text to improve readability. You are right that Tables 1 and 4 (now Table 3) are somewhat similar; however, we believe it is important to include both to maintain transparency regarding the differences between the preliminary and final CMOs. We appreciate your insightful suggestions. In the discussion section, it would be helpful to include a comparison with similar research to better understand the impact of these CMOs on the final study results. Answer: To compare our findings with similar research, we have addressed this in the discussion section titled "The Realist Evaluation Approach." Here, we compare our results with the systematic review by Malengreaux et al. (2022), which examines the use of realist evaluation in health research. This comparison helps contextualize the impact of our identified CMOs and highlights how contextual influences shape outcome measures in realist evaluations. Overall, I believe this paper could be written in a more engaging way. Answer: We have carefully revised the manuscript, making it more engaging and your suggestion above about including the descriptive statistics moving it from the text, has improved Best regards, Anne Møller Lohmann Department of Public Health – Respiratory Diseases and Allergy, Aarhus University and Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark Email: anneml@clin.au.dk Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0326143.r003
Decision Letter - Davor Plavec, Editor Dear Dr. Lohmann, 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 submit your revised manuscript by Jun 12 2025 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. 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 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, Davor Plavec, MD, MSc, PhD, Prof. Academic Editor PLOS ONE Journal Requirements: 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. Additional Editor Comments: Dear Authors, please revise your manuscript in accordance with the reviewer's comments or write a detailed rebuttal on a point-by-point basis. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes ****** Reviewer #2: Dear Authors, Overall, this is a significant improvement. The revised manuscript offers a valuable contribution to understanding the Combined Symptom Medication Score (CSMS) through a realist evaluation framework. The manuscript now more clearly explains the inductive approach used for deriving preliminary themes. However, here are some additional comments to improve: 1. including a brief example or quote in the methods section illustrating the transition from qualitative data to theme could further support transparency. 2. The comparison with prior realist evaluations (e.g., Malengreaux et al., 2022) is appreciated. The discussion could benefit from a more explicit statement on how this study uniquely contributes to the ongoing refinement of CSMS in clinical research beyond confirming prior concerns. 3. While the study highlights threats to internal validity (e.g., preventive medication use, pollen exposure variability), more direct recommendations for mitigating these issues in future CSMS-based trials would strengthen the conclusion. 4. Consider also providing more visual clarity in the CMO tables—perhaps bolding key terms or restructuring to facilitate readability. 5. A few sections of the discussion—particularly those addressing additional symptoms—might be more concise for improved flow. 6. If available, additional details on the development or piloting of the updated CSMS (with ad hoc questions) could help contextualize its use and interpretation. With these minor revisions the manuscript will be well suited for publication. ****** 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 #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.] 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 https://doi.org/10.1371/journal.pone.0326143.r004
Revision 2
25 May 2025 Author Response Reviewer #2: Dear Author, Overall, this is a significant improvement. The revised manuscript offers a valuable contribution to understanding the Combined Symptom Medication Score (CSMS) through a realist evaluation framework. The manuscript now more clearly explains the inductive approach used for deriving preliminary themes. However, here are some additional comments to improve: Answer: Thank you for your kind and constructive feedback. We’re pleased that the revisions have clarified our approach, and that the contribution is valuable. We address your additional comments below. 1. including a brief example or quote in the methods section illustrating the transition from qualitative data to theme could further support transparency. Answer: Thank you for this helpful suggestion. We have now included a participant quote in the Methods section (Step 1) to illustrate how reflections from the focus groups contributed to the development of a theme. This addition aims to enhance transparency around the transition from qualitative data to theme generation. 2. The comparison with prior realist evaluations (e.g., Malengreaux et al., 2022) is appreciated. The discussion could benefit from a more explicit statement on how this study uniquely contributes to the ongoing refinement of CSMS in clinical research beyond confirming prior concerns. Answer: Thank you for this valuable feedback. We have revised the discussion to more clearly state how the study uniquely contributes to the refinement of the CSMS. Specifically, we now highlight how the findings reveal concrete contextual mechanisms—based on the experiences and reflections of individuals with ARC—that may affect the CSMS’s accuracy and applicability. This aligns with COSMIN recommendations and offers a framework for guiding future validation and refinement efforts. 3. While the study highlights threats to internal validity (e.g., preventive medication use, pollen exposure variability), more direct recommendations for mitigating these issues in future CSMS-based trials would strengthen the conclusion. Answer: We have revised the conclusion to more clearly reflect how future studies may explore ways to address the identified contextual factors that can affect the CSMS—such as variability in pollen exposure, use of preventive medication, foreign travel, and the reporting of unrelated or additional symptoms. We now outline how such findings may inform potential future adjustments to the CSMS. However, we have taken care not to propose direct modifications to the instrument itself, as any such changes would require a new psychometric validation study. 4. Consider also providing more visual clarity in the CMO tables—perhaps bolding key terms or restructuring to facilitate readability. Answer: Thank you for this helpful suggestion. As recommended, we have improved the visual clarity of the CMO tables by bolding the most important elements to facilitate easier reading and navigation of key information. 5. A few sections of the discussion—particularly those addressing additional symptoms—might be more concise for improved flow. Answer: Thank you for the suggestion. We have revised the section on additional symptoms to make it more concise and improve the overall flow of the discussion. 6. If available, additional details on the development or piloting of the updated CSMS (with ad hoc questions) could help contextualize its use and interpretation. Answer: Thank you for the comment. We have added a brief description of how the updated CSMS was developed based on input from focus groups with participants in the ILIT.NU trial. We hope this contextualizes its use and interpretation. Best regards, Anne Møller Lohmann Department of Public Health – Respiratory Diseases and Allergy, Aarhus University and Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark Email: anneml@clin.au.dk Attachments Attachment Submitted filename: Response to Reviewer.docx https://doi.org/10.1371/journal.pone.0326143.r005
Decision Letter - Davor Plavec, Editor Understanding the Combined Symptom Medication Score in the light of contexts and mechanisms PONE-D-24-49594R2 Dear Dr. Lohmann, 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, Davor Plavec, MD, MSc, PhD, Prof. Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Authors, your manuscript is now ready for publication in it's current form. Reviewers' comments: https://doi.org/10.1371/journal.pone.0326143.r006
Formally Accepted
Acceptance Letter - Davor Plavec, Editor PONE-D-24-49594R2 PLOS ONE Dear Dr. Lohmann, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. Davor Plavec Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0326143.r007

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