Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data

Habib Hasan Farooqui; Aashna Mehta; Sakthivel Selvaraj

doi:10.1371/journal.pone.0224848

Peer Review History

Original SubmissionMay 24, 2019
21 Jun 2019 Decision Letter - Italo Francesco Angelillo, Editor PONE-D-19-14711 Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data PLOS ONE Dear Dr. Farooqui, 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 July 23, 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. 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In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. 3. We noticed your Discussion has some minor occurrence of overlapping text with the following previous publication, which needs to be addressed: Farooqui, Habib Hasan, et al. "Community level antibiotic utilization in India and its comparison vis-à-vis European countries: Evidence from pharmaceutical sales data." PloS one 13.10 (2018): e0204805. In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. [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: I Don't Know 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: Dr. Farooqui and colleagues present a descriptive analysis of private-sector antibiotic prescribing in India using IQVIA medical audit data from May 2013-May 2014. The study presents descriptive findings that might be of interest to clinicians and public health practitioners. I felt the analysis did not go very deep into the data, although the discussion nicely highlighted key findings. The manuscript could benefit from a deeper analysis of the data, if possible given the dataset. A few comments for consideration: • As the diagnoses in your dataset are not in ICD10 codes, how did you categorize them according to ICD10 codes? It would be helpful to include more on this methodology, perhaps consider including a crosswalk in your supplementary materials. • Why are there no variance estimates? Is this due to the dataset projection methodology? If possible, variance estimates should be included. • It would make your manuscript stronger if you dug deeper into the descriptive data with a few additional analyses. For example, what diagnoses are responsible for the most antibiotic prescriptions by age group? Is there a statistically significant difference between agents and diagnoses in different age groups. • Is there any information on region/geographic area in the dataset. Or provider type (more specifically than general practitioner)? That could be interesting to include and might make the analyses more robust. • What does the ICD code column in Table 1 show? • In the discussion, it makes sense that you discuss over the counter antibiotic sales as that is a contributor to inappropriate antibiotic use. However, I feel you could trim this section down a little since it is not the focus of your analysis. • Please review for grammar and punctuation and ensure all abbreviations are defined at their first use. • I think it would be fine to say IQVIA instead of IMS Health since that is the current company name. Reviewer #2: Although this approach is meriting, the issues of the paper are not meaningful enough and convincing. I do not agree with the conclusion of the authors: data results could not lead to the conclusion “We observed an inappropriate and high antibiotic prescription rates for upper respiratory infections in children age less than 5 years”. Indeed, you used a dataset to estimate the rates and the motif of prescription; to prescribe an antibiotic is associated with a lot of arguments and to estimate if appropriate or not you must read the entire medical report, with biological results (you did not include) the symptoms, the X-rays and so on. To use retrospective medical and clinical data to estimate the rate of AB prescription is a tool we have to develop nowadays, but you can’t conclude on pertinence with this kind of methods. There are different potential methodological reasons for that, the main being that very different clinical presentations could lead to quote a upper respiratory infections; but if the person has comorbidities or other medical condition, maybe an antibiotic could be necessary. You did not adjust your results on the conditions of the patients. The study could be more relevant in presenting the results without this kind of interpretation that can’t be done. ****** 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: 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: Outpatient antibiotic prescription rate_PLOSOne_review.doc Attachment Submitted filename: Plos review v1.pdf https://doi.org/10.1371/journal.pone.0224848.r001
Revision 1
16 Sep 2019 Author Response Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data Response to Reviewers The authors would like to express their gratitude to the reviewers for their insightful comments that have been extremely useful for us in improving the manuscript. Reviewer #1: Dr. Farooqui and colleagues present a descriptive analysis of private-sector antibiotic prescribing in India using IQVIA medical audit data from May 2013-May 2014. The study presents descriptive findings that might be of interest to clinicians and public health practitioners. I felt the analysis did not go very deep into the data, although the discussion nicely highlighted key findings. The manuscript could benefit from a deeper analysis of the data, if possible given the dataset. A few comments for consideration: As the diagnoses in your dataset are not in ICD10 codes, how did you categorize them according to ICD10 codes? It would be helpful to include more on this methodology, perhaps consider including a crosswalk in your supplementary materials. Response: The following has been included in the section ‘Material and Methods’ sub-section ‘Statistical Analysis’ Para 1, page 6 of the manuscript to explain the coding process better: “The diagnosis was categorized into ICD 10 codes through a search on the online index using specific key words in the diagnosis provided in the dataset which was taken directly from the prescriptions. The idea was to code the ICD 10 codes up to the narrowest (most detailed) level possible depending on the extent of details provided in the diagnosis.” Reviewer: Why are there no variance estimates? Is this due to the dataset projection methodology? If possible, variance estimates should be included. Response: We worked with data that was already projected and shared with us by IQVIA (formerly IMS Health). We did not carry out the projection ourselves. We are therefore unable to provide variance estimates. Reviewer: It would make your manuscript stronger if you dug deeper into the descriptive data with a few additional analyses. For example, what diagnoses are responsible for the most antibiotic prescriptions by age group? Is there a statistically significant difference between agents and diagnoses in different age groups. Response: Thank you for the valuable suggestion. We have now included the table with the top 10 diagnosis for antibiotic prescriptions by age groups in the supplementary material. Please see S2 Table in supplementary materials. This has been referred to in the ‘results’ sections, sub-section ‘Antibiotic prescribing across clinical diagnoses’ para 1, page 10-11. Reviewer : Is there any information on region/geographic area in the dataset. Or provider type (more specifically than general practitioner)? That could be interesting to include and might make the analyses more robust. Response: Unfortunately, this information is not available with us. It must be noted that while the data is from private practitioners, it is not only from GPs but also representative of other specializations. We do not however, have information on how the prescription patterns vary across prescriber specializations. Reviewer : What does the ICD code column in Table 1 show? Response: The ICD code indicates each of the 21 chapters. This has been re-labeled in table 1 in the manuscript. Reviewer : In the discussion, it makes sense that you discuss over the counter antibiotic sales as that is a contributor to inappropriate antibiotic use. However, I feel you could trim this section down a little since it is not the focus of your analysis. Response : As suggested the section on over the counter antibiotic sales has been trimmed. Reviewer : Please review for grammar and punctuation and ensure all abbreviations are defined at their first use. Response: The manuscript has been reviewed and revised to address this comment. Reviewer : I think it would be fine to say IQVIA instead of IMS Health since that is the current company name. Response: The manuscript has been reviewed and revised to address this comment. Reviewer #2: Reviewer: This study proposed to estimate outpatient antibiotic prescription rate and patterns in the private sector in India during one year using one medical audit dataset from IMS Health (now IQVIA). The relevance of this study is the increasing room taken by the big data in healthcare sciences and the switch of paradigm that will be linked to this evolution. This manuscript exposed their automated method to estimate antibiotic prescription rates and patterns of prescription according to coding practice in a sample of medical reports from the outpatient private sector in India. To conclude the study reported high antibiotic prescription level overall, by antibiotic classes, age groups, and ICD-10 mapped disease conditions. The topic is highly relevant because antibiotic consumption remains a major public health problem worldwide, promoting the spread of antimicrobial-resistant organisms. Moreover, to measure and survey the antibiotic prescription rate could represent an added value in combination with infection control strategies, for both achieving successful outcomes in patients and impacting the rate of prescriptions. Although this approach is meriting, the issues of the paper are not meaningful enough and convincing. I do not agree with the conclusion of the authors: data results could not lead to the conclusion “We observed an inappropriate and high antibiotic prescription rates for upper respiratory infections in children age less than 5 years”. Indeed, you used a dataset to estimate the rates and the motif of prescription; to prescribe an antibiotic is associated with a lot of arguments and to estimate if appropriate or not you must read the entire medical report, with biological results (you did not include) the symptoms, the X-rays and so on. To use retrospective medical and clinical data to estimate the rate of AB prescription is a tool we have to develop nowadays, but you can’t conclude on pertinence with this kind of methods. There are different potential methodological reasons for that, the main being that very different clinical presentations could lead to quote a upper respiratory infections; but if the person has comorbidities or other medical condition, maybe an antibiotic could be necessary. You did not adjust your results on the conditions of the patients. The study could be more relevant in presenting the results without this kind of interpretation that can’t be done. Response: Thank you for your detailed and useful comments. I agree, the argument around inappropriate use of antibiotics in any clinical diagnosis has to be based not only on symptoms reported by the patient and captured on the prescription but also on sign of fever, laboratory diagnosis and x-rays. However, in India, majority of patients seek care at primary care physicians in the private sector, where they are prescribed empirical antibiotic therapy without any laboratory investigations, microbiologic testing and culture sensitivity. Multiple studies have highlighted these issues and given the epidemiological and microbiological trends and patterns of acute respiratory infections in India, more often, viral aetiology has been identified in community based studies, which do not usually require empirical antibiotic therapy, hence the argument around inappropriate prescription. However, as per your suggestion, the statement has been removed. Specific comments Reviewer: The introduction is in my opinion too focused on India, comparisons with outpatient antibiotic prescription in other countries (Western countries but more similar Eastern countries). Response: Thank you for your valuable comments. Your suggestion has been incorporated in the manuscript in the introduction section. The following has been included in the introduction section (paragraph 2, page 3-4) “Although clinical guidelines on judicious antibiotic…….. does help in reducing the frequency of injudicious antibiotic prescribing” Method section: Reviewer: it is well written even if some typos remain (cf. manuscript) Concerning the representativity of your study population, this sample of GP in the private sector in India. how are recruited the GPs? Volontary? At random? Request? Please explain how could you be sure they are representative of the entire country? Response: Details of the sampling strategy have been added in the section ‘Material and Methods’ sub-section ‘Data Source and Setting’ para 1, page 5 of the manuscript. Please see “This data is collected from a panel comprising of 4600 doctors selected through a multi-stage stratified random sampling, which include… » Further clarification on representativeness has been added in the section ‘Material and Methods’ sub-section ‘Data Source and Setting’ para 1, page 5-6 of the manuscript. Please see « The data is then extrapolated to reflect the prescription pattern of doctors having private practices in towns with population more than a hundred thousand across the country.” Reviewer: You use the population census as the denominator; however aren’t you afraid of the part of this population going to the public sector of healthcare? And so you used a higher number of persons than the targeted population, giving a misinterpretation of the ab prescription rates? What do you think? Response: The proportion of patient visiting the public sector is generally very small in India, especially for outpatient care and therefore the private sector provides a good enough representation of the country in general. We have explained this in the discussion section, para 8 page 15-16 of the manuscript « Therefore, the study is not representative of the prescriptions generated in public sector facilities. This may have resulted in an underestimation of antibiotic prescription rates albeit only marginally, since more than 80% of the population seeks care in private sector and approximately 90% of medicine expenditure occurs in private sector » We have also added the following as a limitation to the discussions section para 8, page 15. “Since we did not have information on the number of the patients accessing general practices in metros and class 1 and 1a towns, we had to rely on the total population to arrive at the prescription rates. This is another limitation of our study.” Reviewer: The dataset did not have the motif of the visit and you coded yourself in ICD -10 codes? From what kind of database? Who did choose the motif of consultation? The pattern of the visit? This is a little surprising as you went to specific data to structured but less specific ones??? Explain the initial data before the transcription in ICD-10 codes. Response: We used the information provided in the IQVIA medical audit dataset on the doctor’s diagnosis on the prescription as the basis for ICD 10 classification. The following has been included in the section ‘Material and Methods’ sub-section ‘Statistical Analysis’ Para 1, page 6-7 of the manuscript to explain the coding process better: “The diagnosis was categorized into ICD 10 codes through a search on the online index using specific key words in the diagnosis provided in the dataset which was taken directly from the prescriptions. The idea was to code the ICD 10 codes up to the narrowest (most detailed) level possible depending on the extent of details provided in the diagnosis.” Reviewer: How did you take into account the fact that the person could come twice in the same week for the same event and first not have Ab than as still ill, has finally been prescribed one treatment. Response: We were unfortunately not able to take this into account due to the nature of our data, which was not individual level. This is a limitation of our study. Discussion section: cf manuscript A bit too long even if interesting. Some extra subject paragraphs that could be taken out in my opinion or shortened. Response: The manuscript has been reviewed and revised to address this comment. References: Some typos and lack of recent literature on that topic. Authors should better screened references databases. Response: The manuscript has been reviewed and revised to address this comment. Some suggestions to help: Antibiotic Prescribing in Outpatient Children: A Cohort From a Clinical Data Warehouse. Grammatico-Guillon L, Shea K, Jafarzadeh SR, Camelo I, Maakaroun-Vermesse Z, Figueira M, Adams WG, Pelton S. Clin Pediatr (Phila). 2019 Jun;58(6):681-690. Durkin MJ, Jafarzadeh SR, Hsueh K, Sallah YH, Munshi KD, Henderson RR, et al. Outpatient Antibiotic Prescription Trends in the United States: A National Cohort Study. Infect Control Hosp Epidemiol. 2018 Feb 27;1–6. Hersh AL, Jackson MA, Hicks LA, the COMMITTEE ON INFECTIOUS DISEASES. Principles of Judicious Antibiotic Prescribing for Upper Respiratory Tract Infections in Pediatrics. PEDIATRICS. 2013 Dec 1;132(6):1146–54. Attachments Attachment Submitted filename: Response to the reviewers.doc https://doi.org/10.1371/journal.pone.0224848.r002
7 Oct 2019 Decision Letter - Italo Francesco Angelillo, Editor PONE-D-19-14711R1 Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data PLOS ONE Dear Dr. Farooqui, 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 October 31, 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, Italo Francesco Angelillo, DDS, MPH Academic Editor PLOS ONE [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 #2: All comments have been addressed Reviewer #3: (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 #2: Partly Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: Yes ****** 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 #2: No Reviewer #3: 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 #2: Yes Reviewer #3: 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 #2: The authors took into account the comments of both reviewers and modified the manuscript accordingly. This improved the response to the objectives of the study and make the article suitable for publication in my opinion. Reviewer #3: Many thanks for allowing me to review this revised manuscript. The authors tried to adequately address the reviewer comments raised in the previous round of review, although they were not able to overcome some shortcomings (e.g. variance estimates, comorbidities and follow-up visits for the same diagnosis were not explored) due to the nature of the study data. However, I believe that inappropriate use of antibiotics is a serious threat to global health, and exploring the pattern of antibiotic prescription among primary care providers represents one of the best tool to promote the appropriateness of use and to control antimicrobial resistance. The revised manuscript could be approved for publication in PLOS ONE journal, after other minor revision. I suggest to add in the limitations section that since the dataset did not include the ICD-10 code, the authors coded themselves the ICD-10 starting from the reason of the visit. It may lead to an inaccurate evaluation. Both the reviewers highlighted lack of recent literature on that topic. All these papers have to be cited and commented: Bianco et al. Infect Drug Resist. 2018;11:2199-2205, Lindberg et al. Scand J Prim Health Care. 2017 Jun;35(2):178-185 (the study findings showed that more than half of the antibiotic prescriptions were dispensed for the diseases of the respiratory system); Davis et al. Antibiotics 2017; 6,4 23, Bert et al. Eur J Public Health. 2017 Jun 1;27(3):506-512 and Napolitano F et al. PLoS One. 2013 Dec 23;8(12):e84177 to emphasize the pivotal role of patients in reducing the inappropriate and excessive utilization of antibiotics. ****** 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 #2: Yes: Dr l Grammatico-Guillon, MD, PhD Reviewer #3: 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.0224848.r003
Revision 2
20 Oct 2019 Author Response Reviewer #2: The authors took into account the comments of both reviewers and modified the manuscript accordingly. This improved the response to the objectives of the study and make the article suitable for publication in my opinion. Response: Many thanks for the positive decision on the manuscript. Reviewer #3: Many thanks for allowing me to review this revised manuscript. The authors tried to adequately address the reviewer comments raised in the previous round of review, although they were not able to overcome some shortcomings (e.g. variance estimates, comorbidities and follow-up visits for the same diagnosis were not explored) due to the nature of the study data. However, I believe that inappropriate use of antibiotics is a serious threat to global health, and exploring the pattern of antibiotic prescription among primary care providers represents one of the best tool to promote the appropriateness of use and to control antimicrobial resistance. The revised manuscript could be approved for publication in PLOS ONE journal, after other minor revision. Response: Many thanks for your encouraging comments and suggestions. We have incorporated them into our manuscript. Comment 1: I suggest to add in the limitations section that since the dataset did not include the ICD-10 code, the authors coded themselves the ICD-10 starting from the reason of the visit. It may lead to an inaccurate evaluation. Response: The suggested limitation has been included in the manuscript in the Discussion section. Comment 2: Both the reviewers highlighted lack of recent literature on that topic. All these papers have to be cited and commented: Bianco et al. Infect Drug Resist. 2018;11:2199-2205, Lindberg et al. Scand J Prim Health Care. 2017 Jun;35(2):178-185 (the study findings showed that more than half of the antibiotic prescriptions were dispensed for the diseases of the respiratory system); Davis et al. Antibiotics 2017; 6,4 23, Bert et al. Eur J Public Health. 2017 Jun 1;27(3):506-512 and Napolitano F et al. PLoS One. 2013 Dec 23;8(12):e84177 to emphasize the pivotal role of patients in reducing the inappropriate and excessive utilization of antibiotics. Response: The suggested literature has been incorporated into the discussion section of the manuscript. Attachments Attachment Submitted filename: Response to the reviewers.doc https://doi.org/10.1371/journal.pone.0224848.r004
23 Oct 2019 Decision Letter - Italo Francesco Angelillo, Editor Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data PONE-D-19-14711R2 Dear Dr. Farooqui, 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, Italo Francesco Angelillo, DDS, MPH Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0224848.r005
Formally Accepted
5 Nov 2019 Acceptance Letter - Italo Francesco Angelillo, Editor PONE-D-19-14711R2 Outpatient antibiotic prescription rate and pattern in the private sector in India: Evidence from medical audit data Dear Dr. Farooqui: 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 Professor Italo Francesco Angelillo Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0224848.r006

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