Safety assessment of sodium zirconium cyclosilicate: A FAERS-based disproportionality analysis

Yongfei Yu; Kaiyu Zhang; Jinglin Gao; Guoshun Huang; Chen Yong; Yuan Wei; Enchao Zhou

doi:10.1371/journal.pone.0320585

Peer Review History

Original SubmissionNovember 12, 2024
12 Nov 2024 Author Response https://doi.org/10.1371/journal.pone.0320585.r001
7 Feb 2025 Decision Letter - Nik Hisamuddin Nik Ab. Rahman, Editor PONE-D-24-48785Safety assessment of sodium zirconium cyclosilicate: a FAERS-based disproportionality analysisPLOS ONE Dear Dr. Zhou, 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 Mar 24 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. 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. We look forward to receiving your revised manuscript. Kind regards, Nik Hisamuddin Nik Ab. 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Please review our guidelines at https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse. 3. Thank you for stating the following financial disclosure: “Our research was supported by the National Natural Science Foundation of China under grant 82474427 to EZ, Jiangsu Natural Science Foundation of China under grant BE2023791 to EZ, Jiangsu Province Leading Talents Cultivation Project for Traditional Chinese Medicine under grant SLJ0319 to EZ, Jiangsu Province Traditional Chinese Medicine Science and Technology Project under grant ZD202007 to EZ and Postgraduate Research & Practice Innovation Program of Jiangsu Province under grant SJCX_0724 to YY.” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 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. [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: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 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: The study investigates adverse events of SZC using FARES data base. The methodology and analysis are appropriate and the authors have recognised the limitations and potential biases. I have a few comments related to the methodology. 1) The authors may wish to expand on how they dealt with duplicate entries and verified each report related SCZ. 2) It is stated that 8,067,923 AE reports were collected from the FAERS database during the study period and after rigorous data cleaning, 1,154 SZC-related AEs were identified for analysis. The authors may wish to provide details of the so called data cleaning” process, especially with respect to reports related SZC. ( number of reports related to SCZ excluded, the reasons for exclusion etc.) Reviewer #2: In the manuscript “Safety Assessment of Sodium Zirconium Cyclosilicate: A FAERS-Based Disproportionality Analysis” Yu et al. describe a retrospective study analyzing adverse effects reported in patients who used sodium zirconium cyclosilicate (SZC), which since 2018 has been a therapeutic agent for the treatment of hyperkalemia. The study analyzes a large number of real-world reports recorded in the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2018 and 2023. Through statistical tests with disproportionality measures, the authors obtained relevant information quantifying the number of adverse event reports. This pharmacovigilance strategy is interesting because traditional qualitative analyzes of large databases are expensive and require long execution times. Thus, quantitative analysis (data mining) represents a faster and more efficient pharmacovigilance tool. Through this strategy, the authors confirmed the known adverse effects of SZC and identified new observations of side effects, covering 21 organ systems. They also highlighted the need for careful clinical monitoring and further studies to confirm associations of reported adverse effects with SZC, as disproportionality analysis does not prove causality. The authors have produced an interesting manuscript containing original and relevant data. There are minor issues that need to be addressed before it is accepted for publication on Plos One. Minor Issues References: The way references are cited needs to be revised to be presented in the same standard. Citations from periodicals are sometimes written in full and in capital letters, sometimes in abbreviated form and in lowercase letters. ****** 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: MAURICIO YOUNES-IBRAHIM ******** [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.0320585.r002
Revision 1
11 Feb 2025 Author Response Dear Editor and Reviewers, Thank you for perspective on our work. Your comments have been extremely helpful for improving the quality of our manuscript. We have reviewed and revised the reference list. Now we ensure that it is complete and correct. Words shown in red are the changes we have made in the manuscript. We have also provided our point-by-point response to the comments from each reviewer, and we have highlighted the changes in the revised manuscript. The complete details of each file is listed. We sincerely hope that you find our responses and modifications satisfactory and consider the manuscript suitable for publication. Response to academic editor: [1)Thank you for stating the following financial disclosure: “Our research was supported by the National Natural Science Foundation of China under grant 82474427 to EZ, Jiangsu Natural Science Foundation of China under grant BE2023791 to EZ, Jiangsu Province Leading Talents Cultivation Project for Traditional Chinese Medicine under grant SLJ0319 to EZ, Jiangsu Province Traditional Chinese Medicine Science and Technology Project under grant ZD202007 to EZ and Postgraduate Research & Practice Innovation Program of Jiangsu Province under grant SJCX_0724 to YY.” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.] Response: Thank you for your reminder. We have confirmed that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The statement has been added in the manuscript and cover letter. [2)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.] Response: Thank you for your helpful guidance. The figures have been uploaded to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool. PACE generated figure files have been uploaded with the revised submission. Response to the reviewer#1’s comments: [1)The authors may wish to expand on how they dealt with duplicate entries and verified each report related SCZ.] Response: Thank you for your detailed review of our method. The drug name was standardized through the Medex_UIMA_1.8.3 system. Reports suspecting Sodium zirconium cyclosilicate as the primary drug associated with AEs were extracted. The FDA-recommended criteria were followed to remove duplicate entries[1, 2]. For identical CASEIDs, the latest FDA_DT was selected; for similar CASEID and FDA_DT, the record with the higher PRIMARYID was selected[3]. We have refined this part in the data source and data processing section of the manuscript. References: 1. Shu Y, He X, Liu Y, Wu P, Zhang Q. A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System. Clin Epidemiol. 2022;14:789-802. https://10.2147/CLEP.S365513 PMID: 35789689 2. Wang Y, Zhao B, Yang H, Wan Z. A real-world pharmacovigilance study of FDA adverse event reporting system events for sildenafil. Andrology. 2024;12(4):785-92. https://10.1111/andr.13533 PMID: 37724699 3. Cui Z, Cheng F, Wang L, Zou F, Pan R, Tian Y, et al. A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say? Front Pharmacol. 2023;14:1259908. https://10.3389/fphar.2023.1259908 PMID: 37954852 [2) It is stated that 8,067,923 AE reports were collected from the FAERS database during the study period and after rigorous data cleaning, 1,154 SZC-related AEs were identified for analysis. The authors may wish to provide details of the so called data cleaning” process, especially with respect to reports related SZC. ( number of reports related to SCZ excluded, the reasons for exclusion etc.)] Response: Thank you for reading the manuscript so carefully. Considering the drug approval timeline, the FAERS database's DEMO module initially contained 9,440,084 reports from the third quarter of 2018 to the fourth quarter of 2023. Following FDA-recommended deduplication protocols, we removed 1,372,161 duplicate entries, retaining 8,067,923 standardized DEMO records. Subsequently, we conducted systematic searches in the DRUG dataset using standardized medication nomenclature, establishing cross-database linkages through the primaryid field. This identifier enabled targeted extraction of 1,154 case records containing demographic and administrative information related to adverse events from the DEMO database. These validated primaryid entries were further utilized to retrieve 2,027 specific AE reports from the REAC database. The consolidated dataset was then subjected to integrative analysis and critical evaluation. The absence of granular clinical metadata precluded comprehensive identification and exclusion of data susceptible to potential bias, constituting a fundamental methodological constraint in FAERS-related investigation. Therefore, well-designed clinical studies are needed in the future to investigate causal associations. Response to the reviewer#2’s comments: [Minor Issues References: The way references are cited needs to be revised to be presented in the same standard. Citations from periodicals are sometimes written in full and in capital letters, sometimes in abbreviated form and in lowercase letters.] Response: Thank you very much for your detailed evaluation of our research. We have reviewed and revised the reference list. We have replaced the journal names in the references by substituting the original full journal titles with standardized abbreviated forms that meet the required guidelines, and have additionally supplemented each reference entry with its corresponding PMID number. We also replaced "doi:" with "https//" to enhance compliance with the journal's formatting guidelines. Now we ensure that it is complete and correct. The changes in references are as follows: 1. Kim MJ, Valerio C, Knobloch GK. Potassium Disorders: Hypokalemia and Hyperkalemia. AMERICAN FAMILY PHYSICIAN. 2023;107(1):59-70. We have replaced "AMERICAN FAMILY PHYSICIAN" with "Am Fam Physician" and have added "PMID: 36689973" to complete the information of this reference. 2.Nilsson E, Gasparini A, Arnlov J, Xu H, Henriksson KM, Coresh J, et al. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. International Journal of Cardiology. 2017;245:277-84. doi: 10.1016/j.ijcard.2017.07.035. We have replaced "International Journal of Cardiology" with "Int J Cardiol" and have added "PMID: 28735756" to complete the information of this reference. 3.Weiss JN, Qu Z, Shivkumar K. Electrophysiology of Hypokalemia and Hyperkalemia. Circulation-Arrhythmia and Electrophysiology. 2017;10(3). doi: 10.1161/circep.116.004667. We have replaced "Circulation-Arrhythmia and Electrophysiology" with "Circ Arrhythm Electrophysiol" and have added "PMID: 28314851" and "e004667" to complete the information of this reference. 4.Llubani R, Vukadinovic D, Werner C, Marx N, Zewinger S, Bohm M. Hyperkalaemia in Heart Failure-Pathophysiology, Implications and Therapeutic Perspectives. Current heart failure reports. 2018;15(6):390-7. doi: 10.1007/s11897-018-0413-9. We have replaced "Current heart failure reports" with "Curr Heart Fail Rep" and have added "PMID: 30421355" to complete the information of this reference. 5.Hoy SM. Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia. DRUGS. 2018;78(15):1605-13. doi: 10.1007/s40265-018-0991-6. We have replaced "DRUGS" with "Drugs" and have added "PMID: 30306338" to complete the information of this reference. 6.Spinowitz BS, Fishbane S, Pergola PE, Roger SD, Lerma EV, Butler J, et al. Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia A 12-Month Phase 3 Study. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. 2019;14(6):798-809. doi: 10.2215/CJN.12651018. We have replaced "CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY" with "Clin J Am Soc Nephrol" and have added "PMID: 31110051" to complete the information of this reference. 7.Jiang Y, Zhou L, Shen Y, Zhou Q, Ji Y, Zhu H. Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database. JOURNAL OF AFFECTIVE DISORDERS. 2024;346:223-9. doi: 10.1016/j.jad.2023.11.025. We have replaced "JOURNAL OF AFFECTIVE DISORDERS" with "J Affect Disord" and have added "PMID: 37956832" to complete the information of this reference. 8.Shu Y, Ding Y, Liu Y, Wu P, He X, Zhang Q. Post-Marketing Safety Concerns With Secukinumab: A Disproportionality Analysis of the FDA Adverse Event Reporting System. FRONTIERS IN PHARMACOLOGY. 2022;13. doi: 10.3389/fphar.2022.862508. We have replaced "FRONTIERS IN PHARMACOLOGY" with "Front Pharmacol" and have added "PMID: 35754494" and "2022;13:862508"to complete the information of this reference. 9.Wang F, Zhou B, Sun H, Wu X. Proarrhythmia associated with antiarrhythmic drugs: a comprehensive disproportionality analysis of the FDA adverse event reporting system. FRONTIERS IN PHARMACOLOGY. 2023;14. doi: 10.3389/fphar.2023.1170039. We have replaced "FRONTIERS IN PHARMACOLOGY" with "Front Pharmacol" and have added "PMID: 37251345" and "2023;14:1170039" to complete the information of this reference. 10.Sakaeda T, Tamon A, Kadoyama K, Okuno Y. Data Mining of the Public Version of the FDA Adverse Event Reporting System. International Journal of Medical Sciences. 2013;10(7):796-803. doi: 10.7150/ijms.6048. We have replaced "International Journal of Medical Sciences" with "Int J Med Sci" and have added "PMID: 23794943" to complete the information of this reference. 11.Shu Y, He X, Liu Y, Wu P, Zhang Q. A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System. CLINICAL EPIDEMIOLOGY. 2022;14:789-802. doi: 10.2147/CLEP.S365513. We have replaced "CLINICAL EPIDEMIOLOGY" with "Clin Epidemiol" and have added "PMID: 35789689" to complete the information of this reference. 12.Wang Y, Zhao B, Yang H, Wan Z. A real-world pharmacovigilance study of FDA adverse event reporting system events for sildenafil. ANDROLOGY. 2024;12(4):785-92. doi: 10.1111/andr.13533. We have replaced "ANDROLOGY" with "Andrology" and have added "PMID: 37724699" to complete the information of this reference. 13.Cui Z, Cheng F, Wang L, Zou F, Pan R, Tian Y, et al. A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say? FRONTIERS IN PHARMACOLOGY. 2023;14. doi: 10.3389/fphar.2023.1259908. We have replaced "FRONTIERS IN PHARMACOLOGY" with "Front Pharmacol" and have added "PMID:37954852" and "2023;14:1259908" to complete the information of this reference. 14.Singh J. International conference on harmonization of technical requirements for registration of pharmaceuticals for human use. Journal of pharmacology & pharmacotherapeutics. 2015;6(3):185-7. doi: 10.4103/0976-500x.162004. We have replaced "Journal of pharmacology & pharmacotherapeutics" with "J Pharmacol Pharmacother" and have added "PMID: 26312010" to complete the information of this reference. 15.Brown EG. Methods and pitfalls in searching drug safety databases utilising the Medical Dictionary for Regulatory Activities (MedDRA). Drug Safety. 2003;26(3):145-58. doi: 10.2165/00002018-200326030-00002. We have replaced "Drug Safety" with "Drug Saf" and have added "PMID: 12580645" to complete the information of this reference. 16.Zhou Q, Du Z, Qu K, Shen Y, Jiang Y, Zhu H, et al. Adverse events of epidiolex: A real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database. ASIAN JOURNAL OF PSYCHIATRY. 2023;90. doi: 10.1016/j.ajp.2023.103828. We have replaced "ASIAN JOURNAL OF PSYCHIATRY" with "Asian J Psychiatr" and have added "PMID: 37949044" and "2023;90:103828"to complete the information of this reference. 17.Steinhart AH, Hemphill D, Greenberg GR. Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysis. The American journal of gastroenterology. 1994;89(12):2116-24. We have replaced "The American journal of gastroenterology" with "Am J Gastroenterol" and have added "PMID: 7977225" to complete the information of this reference. 18.van Puijenbroek EP, Bate A, Leufkens HGM, Lindquist M, Orre R, Egberts ACG. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiology and Drug Safety. 2002;11(1):3-10. doi: 10.1002/pds.668. We have replaced "Pharmacoepidemiology and Drug Safety" with "Pharmacoepidemiol Drug Saf" and have added "PMID: 11998548" to complete the information of this reference. 19.Song Y, Xu Y-l, Lin Y, Zhao B, Sun Q. Fractures due to Aromatase Inhibitor Therapy for Breast Cancer: A Real-World Analysis of FAERS Data in the Past 15 Years. Oncology Research and Treatment. 2020;43(3):96-102. doi: 10.1159/000505376. We have replaced "Oncology Research and Treatment" with "Oncol Res Treat" and have added "PMID: 31945768" to complete the information of this reference. 20.Cornelius VR, Sauzet O, Evans SJW. A Signal Detection Method to Detect Adverse Drug Reactions Using a Parametric Time-to-Event Model in Simulated Cohort Data. Drug Safety. 2012;35(7):599-610. We have replaced "Drug Safety" with "Drug Saf" and have added "PMID: 22702641" to complete the information of this reference. 21.Kinoshita S, Hosomi K, Yokoyama S, Takada M. Time-to-onset analysis of amiodarone-associated thyroid dysfunction. Journal of Clinical Pharmacy and Therapeutics. 2020;45(1):65-71. doi: 10.1111/jcpt.13024. We have replaced "Journal of Clinical Pharmacy and Therapeutics" with "J Clin Pharm Ther" and have added "PMID: 31400296" to complete the information of this reference. 22.Mazhar F, Battini V, Gringeri M, Pozzi M, Mosini G, Marran AMN, et al. The impact of anti-TNFα agents on weight-related changes: new insights from a real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS) database. Expert Opinion on Biological Therapy. 2021;21(9):1281-90. doi: 10.1080/14712598.2021.1948529. We have replaced "Expert Opinion on Biological Therapy" with "Expert Opin Biol Ther" and have added "PMID: 34191656" to complete the information of this reference. 23.Aldahl M, Jensen A-SC, Davidsen L, Eriksen MA, Hansen SM, Nielsen BJ, et al. Associations of serum potassium levels with mortality in chronic heart failure patients. European Heart Journal. 2017;38(38):2890-6. doi: 10.1093/eurheartj/ehx460. We have replaced "European Heart Journal" with "Eur Heart J" and have added "PMID: 29019614" to complete the information of this reference. 24.Desai NR, Kammerer J, Budden J, Olopoenia A, Tysseling A, Gordon A. The Association of Heart Failure and Edema Events between Patients Initiating SZC or Patiromer. Kidney360. 2024;10.34067/kid.0000000586. doi: 10.34067/kid.0000000586. We have replaced "2024;10.34067/kid.0000000586" with "2024;5(12):1835-43" to complete the information of this reference. 25.Thu Kyaw M, Maung ZM. Hypokalemia-Induced Arrhythmia: A Case Series and Literature Review. Cureus. 2022;14(3):e22940-e. doi: 10.7759/cureus.22940. We have added "PMID: 35411269" to complete the information of this reference. 26.Chan YH, Tsai WC, Ko JS, Yin DC, Chang PC, Rubart M, et al. Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing. Circulation. 2 Attachments Attachment Submitted filename: Response to the academic editor and reviewers.docx https://doi.org/10.1371/journal.pone.0320585.r003
21 Feb 2025 Decision Letter - Nik Hisamuddin Nik Ab. Rahman, Editor Safety assessment of sodium zirconium cyclosilicate: a FAERS-based disproportionality analysis PONE-D-24-48785R1 Dear En-chao Zhou , 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, Nik Hisamuddin Nik Ab. Rahman Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0320585.r004
Formally Accepted
Acceptance Letter - Nik Hisamuddin Nik Ab. Rahman, Editor PONE-D-24-48785R1 PLOS ONE Dear Dr. Zhou, 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 Professor Dr Nik Hisamuddin Nik Ab. Rahman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0320585.r005

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