PONE-D-25-27267Development of explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in people with type 2 diabetes: a Delphi survey and consensus meeting.PLOS ONE

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Additional Editor Comments:

Kindly rectify all grammatical errors.

[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

Reviewer #3: Yes

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

Reviewer #1: N/A

Reviewer #2: N/A

Reviewer #3: 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

Reviewer #3: 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: No

Reviewer #3: 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: The paper was generally well written.

Background: Captures the essentials of what the survey is about and the general aim of the paper.

Methodology:Sound

Results and Discussion: Presented in a logical and simplified manner.

Conclusion:It is a reflection of the aims and objectives that the authors sought to obtain.

Authors should declare if they received funding or not for this work.

Reviewer #2: Thank you for submitting this article in an important area. Overall, your work was well reported and provided an interesting read. However, I have a few comments/ suggestions that can improve clarity.

Introduction. You have set the scene well, but I think that there is the opportunity to acknowledge that neither an implicit nor explicit approach to reducing potentially inappropriate medicines is a "fix all". I would also liked to have seen some reference to personalisation of treatment (inferred but not explicit in your description of implicit interpretation on guidelines).

Line 57- "physicians and pharmacists face barriers to implementing guidelines..." - be explicit that you are referring to national and international guidance on prescribing of ADs.

Method

Lines 86-87 Please also include that the explicit definitions were identified by literature as described in the study protocol.

Lines 106-107 "Participants were recruited via email". How were these participants identified in the first instance? Were they from existing relationships within the steering group or did you reach out to special interest groups, etc.

Line 117-"the participants had to complete a questionnaire and indicate" refine to "participants completed a questionnaire and indicated.."

lines 122-132 Were participants provided with an individual report and the start of round 2 to inform them how their responses compared to others participating in the survey? Did you apply analyses e.g. a mixed effects regression model to the data. If not, why not?

Line 155-6 "In other cases, the explicit definitions were considered to be indeterminate (neither validated

156 nor rejected have been neither e in an state"... this sentence does not make sense.

Table 1

Median years since qualification [range] 2008 [1982; 2022]. The median years from qualification is not reported; this is the median YEAR OF qualification.

Figure 1. Whilst this is interesting to see which areas of France were represented in the Delphi study, it would also be interesting to see which healthcare professionals from these regions also participated. you report that you have one Swiss and one Belgian participant, but it would have been interesting to see what type of healthcare professional this was, e.g. GP, community pharmacist, etc.

Line 175 I would open this paragraph describing figure 2 and then outline the timeframe. Currently the reference style made me think the figure also contained dates and not the flow of participants and the evolution of the definitions.

Line 183 "2024.Of " Space required between the end of one sentence and start of another

Discussion

Line 217 "Polypharmacy is very prevalent"- do not need "very"

Line 225 "Explicit tools for use with populations of older adults have been studied extensively"- give examples

Lines 232-250 It feels more organic to lead with existing PIP tools then your tool, highlighting the differences.

Lines 259-262- how can this limitation be adapted for an international audience?

Line 273 Acknowledgments. These seems rather extensive. Other Delhi publications have thanked the participants collectively.

Thank you again for submitting your work for publication.

Reviewer #3: Manuscript Title: Development of explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in people with type 2 diabetes: a Delphi survey and consensus meeting.

General Assessment:

This study presents a well-structured Delphi consensus approach to developing explicit definitions for potentially inappropriate prescriptions (PIPs) of antidiabetic drugs (ADs) in type 2 diabetes mellitus (T2DM). The topic is clinically relevant, given the increasing complexity of T2DM management and the risks associated with inappropriate prescribing. The methodology is robust, and the results are clearly presented. However, some aspects require clarification or improvement before publication. My comments are enumerated below.

Point-by-Point Comments

1. Title and Abstract

• Title: Appropriate and clear.

• Abstract: The abstract succinctly summarizes the study’s objectives, methods, and key findings.

2. Introduction

• Strengths:

o Clearly outlines the need for explicit PIP definitions in T2DM management.

o Justifies the study by highlighting gaps in existing tools (e.g., lack of AD-specific criteria).

• Suggestions:

o Briefly mention the clinical consequences of PIP-ADs (e.g., hypoglycemia, ketoacidosis) earlier to strengthen rationale.

o Clarify why insulin was excluded from the scope (is it due to different prescribing dynamics?).

3. Methods

• Overall: Well-described and methodologically sound.

• Specific Comments:

o Participant Recruitment:

� The target distribution (25% GPs, 25% diabetologists, etc.) is appropriate, but the final sample slightly deviates (e.g., 18.4% GPs). A brief discussion on whether this affected results would be helpful.

� Geographic distribution (mostly France) may limit generalizability. Acknowledging this as a limitation is sufficient.

o Delphi Process:

� The two-round Delphi approach with consensus meetings is rigorous.

� The 75% agreement threshold is standard, but was there any consideration of weighting responses by expertise (e.g., diabetologists vs. pharmacists)?

4. Results

• Participant Demographics:

o Table 1 is clear, but the female percentage for GPs (14%) seems unusually low. Is this representative of the GP population in the region?

• Consensus Definitions:

o The 41 definitions are well-organized into four clinically relevant categories.

o Minor issue: Some definitions (e.g., #35 on metformin and dehydration) are highly specific. Were these derived from real-world cases or guidelines? A brief rationale for inclusion would help.

5. Discussion

• Strengths:

o Compares findings to existing PIP tools (e.g., Beers, STOPP/START).

o Highlights potential applications in clinical decision support systems (CDSS).

• Suggestions for Improvement:

o Clinical Relevance: Discuss how frequently these PIP scenarios occur in practice (e.g., are some rare?).

o Implementation Challenges:

� How feasible are these definitions for automated CDSS use? Some may require complex data (e.g., HbA1c trends, patient-reported symptoms).

o Limitations:

� Acknowledge that the list may not cover all ADs (e.g., thiazolidinediones, as noted).

� The study focused on non-insulin ADs—could future work include insulin?

6. Conclusion

• Succinct and aligned with the study’s goals.

• Consider adding a sentence on next steps (e.g., validation in real-world settings).

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Reviewer #1: Yes:  Dr. Thelma Alalbila Aku

Reviewer #2: No

Reviewer #3: No

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Development of explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in people with type 2 diabetes: a Delphi survey and consensus meeting.

PONE-D-25-27267R1

Dear Dr. Gerard,

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,

Sairah Hafeez Kamran, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: 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 #1: Yes

Reviewer #2: Yes

Reviewer #3: 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 #1: The authors have addressed all the outstanding issues.I identified typographical errors and they have addressed them.

Reviewer #2: Thank you for responding to and actioning comments from the reviewers. Your manuscript is more robust and better explains your processes and details of your research. However, there are a few minor typographical errors that have appeared in the manuscript when it was edited.

Line 127 "period" at the start of the sentence

Lines 309-311 -different font and size.

Reviewer #3: The authors have answered all my questions and concerns. I recommend that the manuscript be accepted.

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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 #1: No

Reviewer #2: No

Reviewer #3: No

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