PONE-D-24-00988Anesthetics drug wastage and preventive strategies: systematic reviewPLOS ONE

Dear Dr. Habte,

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.

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Thank you for submitting your review on this important topic of wastage and financial burden of anesthesia medications. While anesthesia wastage is not limited to medications it forms a sizable portion of the economic burden.I laud the author for choosing a topic of significance even though it has been discussed and studied extensively before. The author has enclosed a review of practices and possible causes of drug wastage across the world. While the review is extensive some concerns include:The manuscript requires thorough grammatical revision as the language currently has many errors.​A more detailed environmental impact of inhalation agents and narcotics waste  if included in the studies  could be mentioned.​A mention of billing challenges in multi dose vials and sterility concerns for drugs like propofol would be pertinent.Some concerns raised by reviewers are attached.==============================

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We look forward to receiving your revised manuscript.

Kind regards,

Shweta Rahul Yemul Golhar, MD

Academic Editor

PLOS ONE

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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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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

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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: Well done manuscript on a topic that is critical especially in developing countries. I appreciate their critical appraisal of all papers. I do request they double check their grammar and typos as there are several throughout the paper.

Reviewer #2: This is a systematic review paper summarized the anesthetics drug wastage in the hospitals based on the public data bases, including google scholar, PubMed and Cochrane library and embase. The authors were able to identify 504 articles related to the topic and found only 16 publications can be selected and used for further analysis after going through the PRISMA. Finally, the author concluded that anesthetic medication waste is a common occurrence worldwide, especially propofol, and suggests some preventive measures to lower drug waste. Overall, although lacking potential novelty, the paper is sound and easy to read, the topic is interesting. However, there are some minors should be addressed before publication.

(1) In the title, the authors proposed the preventive strategies to avoid anesthetic drug wastage, like split dose, is there any limitations using this approach? Like splitting dose could also cause wastage?

(2) Propofol and inhalational anesthetics were suggested to be the most waste drugs in OR. However, is there any difference between inhalational drugs? Like isoflurane or sevoflurane?

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Reviewer #1: No

Reviewer #2: No

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PONE-D-24-00988R1Anesthetics drug wastage and preventive strategies: systematic reviewPLOS ONE

Dear Dr. Habte,

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.

 After obtaining further recommendations, I encourage you to address the comments raised by Reviewer 4. A concern raised previously by myself as well is the practice of multiple use vials and possibility of contamination and billing issues. A more balanced approach would be to suggest practice changes that would not raise concerns raised by reviewer 4 and myself. Since there is not much evidence available to support these practices it can be included as limitations of the study. 

Please submit your revised manuscript by Jul 25 2024 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,

Shweta Rahul Yemul Golhar, MD

Academic Editor

PLOS ONE

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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)

Reviewer #4: All comments have been addressed

Reviewer #5: (No Response)

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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: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: No

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: N/A

Reviewer #5: I Don't Know

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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: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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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

Reviewer #4: Yes

Reviewer #5: Yes

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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: All the comments have been answered by the author and i am satisfied with the author responses. The manuscript is improved by revision.

Reviewer #3: Anesthetic drug wastage may not be the major, or even a minor contributor to drug shortages. Other items such as financial considerations, politics, patents, and even religion may predominate.

In some countries the environmental impact of desflurane and nitrous oxide have removed them from the market.....should more countries adopt that strategy?

Users' education is probably the most important consideration, although anesthesia care providers may be non-plussed by the enormous waste of suture material by surgeons, which far exceeds the $3.90/case quoted by Atcheson. Perhaps the authors might like to highlight anesthesiologists as torch bearers for improved OR efficiency (40% of total hospital expenditure)....less drapes, decreased discarding of full or almost full IV bags, large numbers of surgical instruments and solutions that are not used etc.

The analyses represent 16 studies from 11 countries, including Europe, India, Africa (mostly single studies) and 2 from the US. I see this as a little restricted to label it worldwide...rather a selection of countries.

In some countries like the US, rules, dictated by malpractice suits often, mandate single use vials and discarding of open ampoules or solutions after a certain time even though science has not borne out contamination issues. Reviewing these data and reintroducing them to hospital policy and procedures may also help to revise some current situations (especially before drawn up sugammadex is mandated)

Reviewer #4: In this systematic review, the authors performed a systematic review of the literature to define the financial implication of the anesthetic drugs wastage, and suggest strategies to reduce drug wastage.

Comments:

In my opinion, there are a few points that could be addressed.

1. Although I do appreciate the systematic review performed by the authors, there isn't a lot of literature on the topic. I am not convinced the existing literature is actually helping the authors address the topic other than by highlighting the gaps in the literature.

2. Drug wastage and shortage are important topics, even Moore so since the COVID-19 pandemic. Reductinbg drug wastage is an important point to help reduce drug shortage. The idea of monitoring drug usage and wastage at the institution level, and implementing surveys to monitor it. One aspect that we cannot comprise is safety. Sharing vials between patients etc. should not be promoted as it increases the risk of adverse events.

3. Financial aspects are important, but it is an event more complex topic. We could argue that cost conscious care should be promoted. For example, in many countries sugammadex has become the NMB reversal of choice despite the massive cost of the drug. The same is true for the routine use of dexmedetomidine, fibrinogen concentrate, etc. One should promote cost conscious care in order to reduce cost associated with the use of expansive drugs while cheaper and comparable drugs are available. Is there any data available out there in term of cost-effectiveness for anesthetic drugs? I would suggest the authors to address that.

4. I don't know that the conclusion is truly supported by the results of the systematic review. It is true, but there is an important gap in the literature.

5. As one of my colleagues would argue, the cost of anesthetic drugs only accounts for a small proportion of the overall cost when taking into account surgery, surgical tools, operating room time, ICU costs, etc.

6. I don't think it's been published, but several institutions have saved millions by monitoring drug usage and wastage.

7. The discussion is interesting but they are a lot of other aspects not discussed here.

8. It would be good if the authors could add a central figure or infographic summarizing the topic, their findings, and their suggestions.

Reviewer #5: I do not think that this manuscript meets the standards of Plos One journal. Although I am only reviewing the revised version of this manuscript, but I do not think this is a unique piece of Science. In my opinion, this article is not suitable for publication in Plos. It might be transferred to another journal related to anesthesia/clinical work.

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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: No

Reviewer #3: Yes: Elizabeth Frost

Reviewer #4: Yes: DAVID FARAONI, MD, PhD

Reviewer #5: No

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[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.

Anesthetics drug wastage and preventive strategies: systematic review

PONE-D-24-00988R2

Dear Dr. Meseret Firde Habte,

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.

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Kind regards,

Shweta Rahul Yemul Golhar, MD

Academic Editor

PLOS ONE

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