Drug prescribing and dispensing practices in regional and national referral hospitals of Eritrea: Evaluation with WHO/INRUD core drug use indicators

Senai Mihreteab Siele; Nuru Abdu; Mismay Ghebrehiwet; M. Raouf Hamed; Eyasu H. Tesfamariam

doi:10.1371/journal.pone.0272936

Peer Review History

Original SubmissionApril 10, 2021
9 Nov 2021 Decision Letter - Ashish Kakkar, Editor PONE-D-21-11930 Drug Prescribing and Dispensing Practices in Regional and National Referral Hospitals of Eritrea: Evaluation with WHO/INRUD Core Drug Use Indicators PLOS ONE Dear Dr. Abdu, 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. In particular, the implications of the findings of the study need to be further explored and included in the discussion. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Few comments related to study methods/ discussion are 1. How was non-polypharmacy defined in the study? it is mentioned that two or less drugs were defined as non-polypharmacy. Usually polypharmacy is defined as five or more drugs in a prescription. "Index of non-polypharmacy was measured by dividing average number of drugs by 1.8." Why 1.8? and On page 7, line 136 the formula mentions observed value in the denominator. 2. What is the source of WHO standard as mentioned in the tables? The term optimal value is also used at several places in the text. What is the difference between - WHO standard and optimal values? It is worthwhile to give a table mentioning the optimal values used in the study and their references. 3. The naming of healthcare facilities needs to be uniform in the manuscript text especially tables. 4. The methods section doesn't mention about the country performance indicators. How was the value of 1 calculated for indices of non-polypharmacy and rational injection use? 5. The implications of the study findings need to be discussed in greater details for all stakeholders especially policy makers. 6. There are some language errors and some discrepancies in the numbers mentioned in the text and table. Please submit your revised manuscript by Dec 23 2021 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. 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, Ashish Kakkar, MD DM 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. Please update your Methods section to clarify if the participants gave verbal consent for the information to be used in the study -- did the trained data collectors specifically ask the patients if they consent? Also, please explain why written consent was not used. 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 5. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - http://pharmamedix.in/journals/IJPPR/article/download/107/pdf_28 - https://www.sciencedirect.com/science/article/pii/S1658361213000498?via%3Dihub - https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-017-2097-3 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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: 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: Good day Statistical Analysis: Kindly develop adjusted result Ethical Approval sound appropriate. Please detail ethical approval body with address. Add Reference number of approval letter. Please separate Conclusion and Recommendation. Your key message in a BOX. Please try to use recent reference add or replace more than 5 years old. Reviewer #2: Overall 1) Correction of grammar, spellings and punctuations to improve readability. 2) I notice that the term drug and medicine are used inter-changeably, suggest sticking to the term medicine. Of course you will have to use Drug when referring to INRUD. But in other place make it uniform. Abstract 1) Were the prescriptions collected from in-patients or out-patients or both? its not clear in the abstract 2) Which disciplines were included? coz prescribing patterns will be different. Was it all? Medicine, Surgery, Gyn & Obs, Paediatrics, etc. Again not clear in abstract. 3) In abstract SD is not reported for some parameters 4) Since most of these are likely to be skewed by outlier values, its best to report median and range as well. Introduction 1) Would benefit from a description regarding current practices in the country and a small introduction about its health care system (public vs. private, etc, etc) Methods 1) How big are these hospitals. An indicator about bed strength or an appropriate reference will be helpful for the reader. 2) I now see that this is mainly OPD prescriptions. However, is it all specialties? 3) How many data collectors were involved? Results 1) As mentioned above mean may not be the best way to report. At least mention median and range within brackets Discussion 1) The implications of the study findings are not sufficiently discussed with appropriate references. For example, use of antibiotics 2) Whats the impact of having a mixed group of patients from different specialities 3) Limitations of the study not described adequately. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Mainul Haque 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.0272936.r001
Revision 1
1 Dec 2021 Author Response Author response to Reviewer’s comments We would like to thank our academic editor and reviewers for their invaluable inputs and constructive comments that are helpful to massively improve the quality of the manuscript. After careful consideration of the points raised by academic editor and reviewers, a point-by-point response are as follows: Academic editor 1. How was non-polypharmacy defined in the study? It is mentioned that two or less were defined as non-polypharmacy. Usually polypharmacy is defined as five or more drugs in a prescription. “Index of non-polypharmacy was measured by dividing average number of drugs by 1.8”. Why 1.8? And on page 7, line 136 the formula mentions observed value in the denominator. Response: It is well noted. The definition of polypharmacy in the manuscript was inappropriate and therefore omitted from the text. Besides, the statement “Index of non-polypharmacy was measured by dividing average number of drugs by 1.8” was a typing error and therefore removed from the text. Furthermore, in the result section of the study the concept of “Index of non-polypharmacy was measured by dividing the optimal value (taken as 1.8) by the average number of drugs”. The index of non-polypharmacy was expressed in terms of the average number of drugs per prescription. 2. What is the source of WHO standard as mentioned in the tables? The term optimal value is also used at several places in the text. What is the difference between- WHO standard and optimal values? It is worthwhile to give a table mentioning the optimal values in the study and their references. Response: The reference for the optimal values was cited. There is no difference between the WHO standard and optimal values (used interchangeably). Moreover, an additional table (1) that mentions the WHO standard (optimal values) for all the three indicators alongside their references is added in the method section. 3. The naming of healthcare facilities needs to be uniform in the manuscript especially tables. Response: Accepted 4. The methods section doesn’t mention about the country performance indicators. How was the value of 1 calculated for indices of non-polypharmacy and rational injection use? Response: The country performance indicators for indices of non-polypharmacy and rational injection use was calculated by the concept (optimal value/observed value). The optimal value for non-polypharmacy was taken as 1.8, whereas the optimal value for rational injection use was taken as 24.1. Moreover, the observed value was taken as the overall (average) of the hospitals in each item within the indicators. Optimal index that yielded more than one was taken as one as the maximum value of the optimal index is one. The above-mentioned calculation approach for the country performance indicators was included in the ‘method’ section within the revised manuscript. 5. The implications of the study findings need to be discussed in greater details for all stakeholders especially policy makers. Response: Accepted. The implications of the study findings are discussed in greater details for all stakeholders. The discussion section is modified in the revised manuscript. 6. There are some language errors and some discrepancies in the numbers mentioned in the text and tables. Response: Accepted. A massive editing is made on the manuscript. We have made 320 insertions, 236 deletions, 2 moves and 13 formatting in the revised section. Accordingly, the reference section is fully revised. Please refer the ‘revised manuscript with track changes’. Reviewer 1 -Statistical analysis: kindly develop adjusted result Response: Adjusted result could not be obtained as there is only one independent variable namely, hospital. All the other variable such as average number of medicines per prescription, average consultation and dispensing time and so on are assessed on their potential difference across the hospitals. -Ethical approval sound appropriate. Please detail ethical approval body with address. Add Reference number of approval letter. Response: Accepted -Please separate conclusion and recommendation. Response: Accepted. -Your key message in a box. Response: The key message is already included in the separated recommendation section. -Please try to use recent references add or replace more than 5 years old. Response: This is a very important comment. Our paper has been prepared before 2 years. Hence, your comment is valuable and we included recent available studies in the introduction and discussion sections, while removing too old references. Besides, for WHO and other guidelines that were prepared a long time ago and which were used as a source material for the methodology we preferred to keep them in the references. Reviewer 2 1. Correction of grammar, spellings and punctuations to improve readability. Response: Accepted. A massive editing is made on the manuscript. We have made 320 insertions, 236 deletions, 2 moves and 13 formatting in the revised section. Accordingly, the reference section is fully revised. Please refer the ‘revised manuscript with track changes’. 2. I notice that the term drug and medicine are used interchangeably, suggest sticking to the term medicine. Of course you will have to use Drug when referring to INRUD. But in other place make it uniform. Response: Accepted. Where appropriate, the term ‘drug’ is replaced with the term ‘medicine’. Abstract 1. Were the prescriptions collected from in-patients or out-patients or both? It’s not clear in the abstract. Response: It was from out-patients. 2. Which disciplines were included? Coz prescribing patterns will be different. Was it all? Medicine, Surgery, Gyn & Obs, Paediatrics, etc. Again not clear in the abstract. Response: All medical specialties (disciplines) were included. 3. In abstract SD is not reported for some parameters. Response: Accepted. Standard deviation is reported for all parameters expressed as M (SD). 4. Since most of these are likely to be skewed by outlier values, its best to report median and range as well. Response: Accepted. We reported it as mean for ease of comparison of the values with that of the WHO standard. Besides, at times median value is important we reported it. For instance, average consultation and dispensing time. Introduction 1. Would benefit from a description regarding current practices in the country and a small introduction about its healthcare system (public vs. private, etc, etc) Response: Accepted. The current practices in the country is included in the introduction. Moreover, a small introduction about the Eritrean healthcare system is given in the method section (study design and setting sub-section). Methods 1. How big are these hospitals? An indicator about bed strength or an appropriate reference will be helpful for the reader. Response: All the study sites (hospitals) are one of the biggest hospitals in the country. Orotta and Halibet hospitals are national referral hospitals that serves patients from all around the country. They are situated in the capital city of Eritrea (Asmara) and considered as a tertiary level services that provides lots of services such as out-patient, in-patient, maternity, paediatrics, and surgery and so on. Furthermore, the rest six hospitals are regional referral hospitals that serves patients referred or self-referred within the region they locate. They are considered as secondary level of service and are bigger in nature. 2. I now see that this is mainly OPD prescriptions. However, is it all specialties? Response: Yes, it was from all specialties. 3. How many data collectors were involved? Response: A total of 20 data collectors were involved in the study. Results 1. As mentioned above mean may not be the best way to report. At least mention median and range within brackets. Response: Accepted. At times Md (IQR) is important we reported it in some parameters like average number of medicines per prescription, average consultation and dispensing time. Discussion 1. The implications of the study findings are not sufficiently discussed with appropriate references. For example, use of antibiotics. Response: Accepted. The implications of the study findings are expressed in detail in the revised manuscript. 2. What is the impact of having a mixed group of patients from different specialties? Response: It helps to get a complete picture of the rational use of medicines within a hospital. 3. Limitations of the study not described adequately. Response: Accepted. We explored the possible limitations we have in the study and added in the revised manuscript. Kind regards Nuru Abdu (BPharm) On behalf of the authors Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0272936.r002
22 Jun 2022 Decision Letter - Ashish Kakkar, Editor PONE-D-21-11930R1Drug Prescribing and Dispensing Practices in Regional and National Referral Hospitals of Eritrea: Evaluation with WHO/INRUD Core Drug Use IndicatorsPLOS ONE Dear Dr. Abdu, 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 Aug 06 2022 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. 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, Ashish Kakkar, MD DM 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 (if provided): The authors have addressed majority of the reviewers' and editor's comments. Few minor comments: 1. The tables should include SD wherever mean is mentioned. Either of them (Mean SD/ Median IQR) be reported for each variable depending upon distribution of data values. 2. Table 1 has typo. Percent of drugs adequately labelled! 3. There is discrepancy in the average number of drugs per encounter mentioned in abstract, main results, discussion and the table 2. Needs to be rechecked 4. Several statements in the discussion lack appropriate references viz. irrational and overuse of antibiotics...... , injectable preparations.... 5. Limitations need to include implications of having a mixed group of patients from various specialties. 6. Discussion needs to be rechecked for consistency and appropriate references. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 #1: Yes 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 #1: Yes Reviewer #3: No ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Accept. As Comments are addressed I would to recommend the should be accepted and published in Plos One Reviewer #3: The study addresses an important health care issue of the developing nations which can be controlled with appropriate measures. Prescription, patient care and facility indicators are good source of information about the rational use of medicines in a particular region which is the primary objective of the study. Keeping WHO indices as optimum values for comparison of the rational medicine use parameters is appreciable, though these values are described differently in several published papers. Though several similar studies have been reported earlier, region specific knowledge would be useful to plan further interventions in improving the deficient indices in Eritrea. The calculation of indices for the indicators and ranking the facilities based on the indices is a good initiative which only a few papers have reported earlier. The authors have answered and followed the editor and reviewer comments to a large extent. However a few more corrections are required in the language and grammar to make it easy for the readers to understand in the first read. Some of these corrections are listed below: Introduction: Line 72 must be 'ensuring' Methods: Line 80- ' September 1 to January 31, 2018' year for September to be mentioned Tables 2, 5 : The abbreviations M, Md, IQR to be expanded in foot note. Column headings could be made appropriate for all the values described in the table. Values in Table 4 represent time, but the column heading does not mention time. References: Many are incomplete, example - Ref 1 is incomplete. Web pages are without a url. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Mainul Haque Reviewer #3: Yes: Jayanthi M ******** [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.0272936.r003
Revision 2
25 Jun 2022 Author Response Author response to editor’s and reviewer’s comments We would like to thank our academic editor and reviewers for their invaluable inputs and constructive comments that are helpful to massively improve the quality of the manuscript. After careful consideration of the points raised by academic editor and reviewers, a point-by-point response are as follows: Academic editor 1. The tables should include SD wherever mean is mentioned. Either of them (Mean SD/Median IQR) be reported for each variable depending upon distribution of data values. Response: Thank you for this comment. SD is included wherever mean is mentioned. Besides, the authors preferred to report both the mean (SD) and median (IQR). Mean (SD) is used for ease of comparison with the WHO standard values and median (IQR) is included as some variables have outliers. 2. Table 1 has typo. Percent of drugs adequately labelled! Response: Thank you for pointing out this issue. The typos error in table 1 is corrected in the revised manuscript. 3. There is discrepancy in the average number of drugs per encounter mentioned in the abstract, main results, discussion and the table 2. Needs to be rechecked. Response: Comment is addressed in the revised manuscript. 4. Several statements in the discussion lack appropriate references viz. irrational and overuse of antibiotics……., injectable preparations……….. Response: Thank you for the great comment. The discussion section is revised and where necessary citations are added. Besides, some statements used as implications are the authors’ own ideas. 5. Limitations need to include implications of having a mixed group of patients from various specialties. Response: Thank you for this comment. The study sites are regional and national referral hospitals having various specialties (disciplines). Thus, the study involved a mixed group of patients. So, the authors do not see the importance of adding it in the limitation section. 6. Discussion needs to be rechecked for consistency and appropriate references. Response: Comment well noted. Necessary changes are made in the revised manuscript. Reviewer 1 -Accept. As comments are addressed, I would like to recommend they should be accepted and published in PLOS ONE. Response: Thank you for your review. Reviewer 2 -Introduction: Line 72 must be ‘ensuring’ Response: Thank you for your comment. It was corrected in the revised manuscript. -Methods: Line 80- ‘September 1 to January 31, 2018’ year for September to be mentioned. Response: Comment well taken. Addressed in the revised manuscript. -Tables 2, 5: The abbreviations M, Md, IQR to be expanded in foot note. Response: Comment well taken. Addressed in the revised manuscript. -Column headings could be made appropriate for all the values described in table. Values in Table 4 represent time, but the column heading does not mention time. Response: Thank you for your suggestion. For ease of understanding, the authors added ‘minute’ and ‘second’ alongside the values for the consultation and dispensing time, respectively. -Many are incomplete, example – Ref 1 is incomplete. Web pages are without a URL. Response: Thank you for pointing out this issue. References are updated in the revised version. Kind regards Nuru Abdu (BPharm) On behalf of the authors Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0272936.r004
1 Aug 2022 Decision Letter - Ashish Kakkar, Editor Drug Prescribing and Dispensing Practices in Regional and National Referral Hospitals of Eritrea: Evaluation with WHO/INRUD Core Drug Use Indicators PONE-D-21-11930R2 Dear Dr. Abdu, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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 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, Ashish Kakkar, MD DM Academic Editor PLOS ONE Additional Editor Comments (optional): The authors need to correct a minor typo in Table 1 that was mentioned in the comments - "Percent of drugs "actually" labelled. - It should be "adequately" labelled. Reviewers' comments: https://doi.org/10.1371/journal.pone.0272936.r005
Formally Accepted
10 Aug 2022 Acceptance Letter - Ashish Kakkar, Editor PONE-D-21-11930R2 Drug Prescribing and Dispensing Practices in Regional and National Referral Hospitals of Eritrea: Evaluation with WHO/INRUD Core Drug Use Indicators Dear Dr. Abdu: I'm 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 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 plosone@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. Ashish Kakkar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0272936.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .