Trends in opioid prescribing practices in South Korea, 2009–2019: Are we safe from an opioid epidemic?

Noo Ree Cho; Young Jin Chang; Dongchul Lee; Ji Ro Kim; Dai Sik Ko; Jung Ju Choi

doi:10.1371/journal.pone.0250972

Peer Review History

Original SubmissionJanuary 16, 2021
18 Mar 2021 Decision Letter - Vijayaprakash Suppiah, Editor PONE-D-21-01681 Trends in opioid prescribing practices in South Korea, 2009-2019: are we safe from an opioid epidemic? PLOS ONE Dear Dr. Ko, 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 Apr 24 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. 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The following resources for replacing copyrighted map figures may be helpful: USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/ The Gateway to Astronaut Photography of Earth (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/ Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/ Landsat: http://landsat.visibleearth.nasa.gov/ USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/# Natural Earth (public domain): http://www.naturalearthdata.com/ 3. In the Methods section, please provide further details on how opioid drugs were stratified for analysis. [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: Partly 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: Manuscript Number: PONE-D-21-01681 Title: Trends in opioid prescribing practices in South Korea, 2009-2019: are we safe from an opioid epidemic? Summary I appreciate the opportunity to review this interesting report. This is a nationwide cross-sectional study in Korea that have shown opioids outpatient prescriptions from 2009 through 2019 to ensure that Korea are indeed free from an opioid epidemic. Major Strengths This is an interesting article that first describe an 11-year trend of opioids prescription in South Korea using nationwide data. Major Weakness 1. Please more specify the objectives of the study in the introduction 2.Please describe more specific information of opioids. In addition, I wonder why the fentanyl patch was not included. 3.The authors indicate that over half of South Korean residents (53%) were prescribed opioids at least once in 2019. I think it is overrated. 4. In my opinion, there need some flow chart that represents inclusion and exclusion of the samples. 5. There was no information on the definition of chronic opioids use. Reviewer #2: 63 “no issue” clarify statement. references? 71 “free from epidemic; how is this defined 91 state definition of “strong” here, explain how this relates to MME/day and limits of not using MME/day 124 “each year” - actually the mean value, clarify this. Is this meaningful? 126 “The number of total opioid prescriptions in 2019 was equal to 53% of the population of South Korea.” 128 In 2012 to 2013 there is a large change. This is the most important issue that needs to be addressed in the revision: why did this occur? Was there a change in data used? Was there a change in governmental regulation of opioids? Was there a change of opioid availability? Were new opioid products being introduced into the market? Were some drugs reclassified as opioids? Was there a change in how much could be dispensed by pharmacies, hence more prescriptions for the same amount of opioid? And so forth… The issue is that the paper rests on the tenuous data on the number of prescriptions and there is a significant change at this time. This may not correlate with increasing MME/day or with abuse, misuse, or overdose deaths. A thorough explanation of the reasons for this change must be explored to justify any conclusions drawn. 130 Was Sejong-si an outlier in terms of opioid prescription that could account for per capita changes? 255 greatest “percentage” increase 264 access must be addressed. Were pharmacies and specialist prescribers distributed equally in all districts? Did, for example, high prescription districts have major cancer treatment centers that others did not, etc. 265-269 simply incorrect. ER/LA opioids in the USA are problematic because the MME/day is much higher in these preparations. It is not known if this is the case in South Korea or if the ER/LA prescriptions written in South Korea correlate with higher MME/day prescribed. Without knowing this, no conclusion can be drawn about the need for regulation 276 “addiction to illicit opioids” 278-279 Possibly true but this conclusion cannot be drawn from the data presented. Revise “is needed” to “should be considered” 280-298 The main driving issue for regulatory change in the USA was overdose deaths - morbidity and mortality are not addressed in this data, and it is suggested that a national database of such data be established if it does not exist. ****** 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:** ADRIAN BARTOLI MD [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. 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Revision 1
3 Apr 2021 Author Response Editor's Comments Comment 1: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response: Thank you for your observation and feedback. We have thoroughly reviewed your style requirements and have formatted the manuscript accordingly. If there are any further issues, please let us know. Comment 2: We note that Figure 2 in your submission contains map images, which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software (Google Maps, Street View, and Earth). For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: (1) You may seek permission from the original copyright holder of Figure 2 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” (2) If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. The following resources for replacing copyrighted map figures may be helpful: USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/ The Gateway to Astronaut Photography of Earth (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/ Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/ Landsat: http://landsat.visibleearth.nasa.gov/ USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/# Natural Earth (public domain): http://www.naturalearthdata.com/ Response: Thank you for your advice. We used the R package “Kormap” to download a map of South Korea that shows all the administrative districts. The “Kormap” R package is a transformation of the shape file of the South Korea's map from the Statistical Geographic Information Service for utilization in R. Its license is Korea Open Government License Type 1. It allows the document to be copied, redistributed, remixed, and transformed for any purpose, even commercially, which is very similar to CC-BY 4.0. We received permissions from both the Statistical Geographic Information Service and Kormap’s creator to it use in our work under CC-BY 4.0 license. We have attached these permissions and updated the method. Line 124: “We used the R package, “Kormap,” to download South Korea's map that shows all the administrative districts. The “Kormap” package is a transformation of the shape file of South Korea's map from the Statistical Geographic Information Service for utilization in R. The “Tmap” R package was used to visualize the administrative districts' disparity in opioid prescriptions in South Korea.” Comment 3: In the Methods section, please provide further details on how opioid drugs were stratified for analysis. Response: Thank you for your kind comment. We have updated the manuscript as advised. Reviewers' Comments: Reviewer #1: Manuscript Number: PONE-D-21-01681 Title: Trends in opioid prescribing practices in South Korea, 2009-2019: are we safe from an opioid epidemic? Summary I appreciate the opportunity to review this interesting report. This is a nationwide cross-sectional study in Korea that has shown opioids outpatient prescriptions from 2009 through 2019 to ensure that Korea is indeed free from an opioid epidemic. Major Strengths This is an interesting article that first describe an 11-year trend of opioids prescription in South Korea using nationwide data. Major Weakness Comment 4: Please more specify the objectives of the study in the introduction Response: Thank you for your kind comment. We have specified the objectives in the introduction based on your feedback. Please see the inclusion below: Line 68: "Accordingly, we aimed to examine the opioid outpatient prescription trends from 2009 through 2019 using the following strategies: (1) classification of opioids by potency and formula; (2) changes in the opioid outpatient prescriptions nationally each year; (3) geographical differences in the opioid outpatient prescriptions." Comment 5: Please describe more specific information of opioids. In addition, I wonder why the fentanyl patch was not included. Response: Thank you for your valuable feedback. We apologize for not explaining the meaning sufficiently. We have updated the manuscript by specifying the classification of opioids. The fentanyl patch has also been included in the revised manuscript. Line 93: “We defined strong opioids as those which are equivalent to or higher than morphine’s potency—the morphine milligram equivalents (MME) conversion factor is equal to or higher than 1 and is available in South Korea. The strong opioids were morphine, hydrocodone, fentanyl (including transdermal patches), hydromorphone, and oxycodone. The weak opioids were codeine, dihydrocodeine, tapentadol, and tramadol.” Comment 6: The authors indicate that over half of South Korean residents (53%) were prescribed opioids at least once in 2019. I think it is overrated. Response: Thank you for your comment. We agree with your statement that it is overrated and have, therefore, corrected it. Please see correction below: Line 132: "The total opioid prescriptions in 2019 was equal to 53% of the South Korean population." Comment 7: In my opinion, there need some flow chart that represents inclusion and exclusion of the samples. Response: Thank you for your kind comment. We added the flowchart as Figure 1. Furthermore, based on your comment, we have improved its readability. Comment 8: There was no information on the definition of chronic opioids use. Response: Thank you for your feedback. We have updated the definition of chronic opioid use from reference 9 (Oh TK, Jeon Y-T, Choi JW. Trends in chronic opioid use and association with five-year survival in South Korea: a population-based cohort study. Br J Anaesth. 2019;123(5):655-63.) Line 64: " A recent study reported that patients with chronic use (over 90 days of continuous supply) of weak and strong opioids increased between 2002 and 2015." Reviewer #2: Comment 9: Line 63 “no issue” clarify statement. References? Response: Thank you for your advice. We have corrected it and added a reference. Line 61: "The misuse of prescription opioids and related mortality have not been an issue in Korea [9]." Comment 10: Line 71 “free from epidemic”; how is this defined. Response: Thank you for your kind comment. We agreed that "free from epidemic" is subjective and hard to define. In addition, in the last paragraph of the introduction, it is unwise to not specify the objectives of our study. Therefore, we have corrected the last sentence of the introduction as follows: Line 68: "Accordingly, we aimed to examine opioid outpatient prescription trends from 2009 through 2019 using the following strategies: (1) classification of opioids by potency and formula; (2) changes in the opioid outpatient prescriptions nationally each year; (3) geographical differences in the opioid outpatient prescriptions Comment 11: Line 91 state definition of “strong” here, explain how this relates to MME/day and limits of not using MME/day Response: Thank you for your advice. We had originally requested the Health Insurance Review and Assessment Service Database in South Korea for the number of prescriptions of individual drugs. The prescribing information of an individual drug is essential to calculate the MME/day. However, their policy prohibits them from sharing individual drug prescribing information. The policy indicates that prescribing data can be shared when more than four commercial companies provide the same drug with the same dose. In South Korea, many opioids are provided by individual companies, such as Pfizer and Janssen. Therefore, the only option to retrieve the opioid prescribing information is to categorize opioids into groups, so that there are over four companies. To overcome this limitation, we classified opioids as strong and weak. We defined strong opioids as those which were equivalent to or higher than morphine’s potency, for which the MME conversion factor is equal to or higher than 1. We think we can identify the trends and changes in the opioid outpatients prescribing patterns using this strategy. Please consider our feedback in this regard. Comment 12: Line 124 “each year” - actually the mean value, clarify this. Is this meaningful? Response: We thank you for the feedback. We have adjusted the sentence based on your comments. We think this sentence can guide the readers to Table 1 and make it easier for them to understand our study. Line 131: "From 2009 to 2019, an average of 23.2 million opioid prescriptions were issued from outpatient departments in South Korea." Comment 13: Line 126 “The number of total opioid prescriptions in 2019 was equal to 53% of the population of South Korea.” Response: Thank you for your kind correction. We agreed that it is overrated and have, therefore, corrected it accordingly. Comment 14: Line 128 In 2012 to 2013 there is a large change. This is the most important issue that needs to be addressed in the revision: why did this occur? Was there a change in data used? Was there a change in governmental regulation of opioids? Was there a change of opioid availability? Were new opioid products being introduced into the market? Were some drugs reclassified as opioids? Was there a change in how much could be dispensed by pharmacies, hence more prescriptions for the same amount of opioid? And so forth… The issue is that the paper rests on the tenuous data on the number of prescriptions and there is a significant change at this time. This may not correlate with increasing MME/day or with abuse, misuse, or overdose deaths. A thorough explanation of the reasons for this change must be explored to justify any conclusions drawn. Response: Thank you for your kind comment. We have updated the discussion, substantially. Line 262: “Opioid outpatient prescriptions’ growth was steep until 2013, both nationally and in most administrative districts, however, this growth declined between 2013 and 2019. Since propofol related mortality and misuse became an issue in South Korea, it was classified as a psychotropic agent and regulated from 2011. In 2012, the Ministry of Health and Welfare and the Ministry of Food and Drug Safety in South Korea announced a regulation to strengthen the management of all stages of manufacturing, distribution, and prescription to prevent the misuse of opioids and psychotropic drugs [21]. Due to Drug Utilization Review’s (DUR) improvement, drugs in the same efficacy group and those with the same ingredients can be confirmed in the DUR, so that drugs are not prescribed excessively or duplicated. These strict government regulations seem to have caused the decrease in the opioid outpatient prescriptions’ growth rate in 2013.” Comment 15: Line 130 Was Sejong-si an outlier in terms of opioid prescription that could account for per capita changes? Response: We appreciate your feedback regarding this. The opioid outpatient prescription trends in Sejong-si are different from other administrative districts. It decreases by years (APC -7 from 2012 to 2019). However, the rate of total opioid prescription per 1000 persons in 2019 was 300.4, which is lower than other regions. We had originally omitted the data from Sejong-si. However, the trends (decrease in the growth rate of total, strong, and ER/LA opioids from 2013) were not different nationally when the analysis was performed without the data from Sejong-si. Since this study's primary purpose is to help the government create regulations related to opioids, we decided not to omit the data from Sejong-si. Comment 16: Line 255 greatest “percentage” increase Response: Thank you for your kind comment. We have corrected the sentence. Line 259: “The prescriptions for strong opioids had the greatest percentage increase; however, it accounts for a small proportion of total opioid prescriptions.” Comment 17: Line 264 access must be addressed. Were pharmacies and specialist prescribers distributed equally in all districts? Did, for example, high prescription districts have major cancer treatment centers that others did not, etc. Response: Thank you for this observation. We agreed with your comment and have addressed the effect of discrete distribution of tertiary hospitals related to our results. Line 280: “Tertiary hospitals including cancer treatment centers located in densely populated metropolitan cities, especially Seoul in South Korea. However, the common administrative district with a high prescription rate per 1000 persons of total, strong, and ER/LA opioids was Jeollabuk-do. This may indicate that this area requires opioid education for both prescribers and pharmacists, and enhanced regulations.” Comment 18: Line 265-269 simply incorrect. ER/LA opioids in the USA are problematic because the MME/day is much higher in these preparations. It is not known if this is the case in South Korea or if the ER/LA prescriptions written in South Korea correlate with higher MME/day prescribed. Without knowing this, no conclusion can be drawn about the need for regulation Response: Thank you for your feedback. We agree with you and have significantly revised the section as follows: Line 286: “By comparing our findings with data from the US, we found that strong opioids occupy a larger portion of the total opioids in the US than in South Korea. The rate of prescription per 1000 persons of total opioids and strong opioids were 588.5 in 2017 and 206.7 in 2009 in the USA. Whereas in South Korea, they were 499.7 in 2017 and 15.2 in 2019. Therefore, it can be safely postulated that our government regulations regarding opioid prescriptions has effectively prevented the excessive prescription of strong opioids. The rate of ER/LA prescriptions in South Korea was higher than that in the US. However, due to the level of our data, we were not able to calculate ER/LA prescriptions’ MME/day. Thus, the higher ER/LA prescription rate in South Korea, than that in USA, was not sufficient to provoke the policymakers to create regulations on ER/LA opioid prescriptions in South Korea. Further studies are required to access the individual drug data level to calculate ER/LA opioids’ MME/day.” Comment 19: Line 276 “addiction to illicit opioids” Response: Thank you for pointing this out. We have corrected per your suggestion. Comment 20: Lines 278-279 Possibly true but this conclusion cannot be drawn from the data presented. Revise “is needed” to “should be considered” Response: Thank you for your kind suggestion. We have corrected it accordingly. Comment 21: Lines 280-298 The main driving issue for regulatory change in the USA was overdose deaths - morbidity and mortality are not addressed in this data, and it is suggested that a national database of such data be established if it does not exist. Response: Thank you and we agreed with your comments. We have updated the last paragraph of the discussion section, as follows: Line 314: "In addition, this data contained no clinical information, including the reason opioids were prescribed, demographic information, or longitudinal data linking patients to clinical outcomes, such as opioid overdose morbidity and mortality." Attachments Attachment Submitted filename: Response_to_Reviewers.docx https://doi.org/10.1371/journal.pone.0250972.r002
19 Apr 2021 Decision Letter - Vijayaprakash Suppiah, Editor Trends in opioid prescribing practices in South Korea, 2009-2019: Are we safe from an opioid epidemic? PONE-D-21-01681R1 Dear Dr. Ko, 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, Vijayaprakash Suppiah, PhD Academic Editor PLOS ONE 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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: (No Response) ****** 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: (No Response) ****** 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: (No Response) ****** 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: No https://doi.org/10.1371/journal.pone.0250972.r003
Formally Accepted
3 May 2021 Acceptance Letter - Vijayaprakash Suppiah, Editor PONE-D-21-01681R1 Trends in opioid prescribing practices in South Korea, 2009-2019: Are we safe from an opioid epidemic? Dear Dr. Ko: 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. Vijayaprakash Suppiah Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0250972.r004

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