-->PONE-D-25-52812-->-->Addressing the Disposal of Unused and Expired Medications in Saudi Households: Time to bridge the regulatory gaps-->-->PLOS One

Dear Dr. Abdulsalim,

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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Dawit Getachew Gebeyehu, MPH

Academic Editor

PLOS One

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The researchers would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support (APC-QU- (2025). The authors would also like to express their gratitude to all participants of this study.

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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?

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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-->3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: No

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-->4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: No

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: The manuscript is well written but still has some areas to be improved in the introduction and discussion section. The statistical results are not sure to me, hence i would recommend to confirm about them.

Reviewer #2: The topic is important and suitable for PLOS ONE because improper household storage and disposal of medicines can have public health and environmental implications, and the paper addresses a policy-relevant gap in Saudi Arabia. However, i have some comments:

1. The design is described inconsistently, and you should correct the study design label everywhere: the manuscript repeatedly calls this a “prospective cross-sectional survey,” which is internally contradictory terminology for a one-time questionnaire survey. Please revise to “cross-sectional survey” unless you truly followed respondents over time (which is not described).

2. The data collection period is unclear and inconsistent across sections, and this must be reconciled: the front matter/abstract describes a “three-month period,” while the Methods state data collection from 20 December 2022 to 28 February 2023 (about ~2–2.5 months). Please make the period consistent across Abstract, Methods, and Results.

3. The sampling approach is not transparent enough to evaluate bias: you state “proportional sampling was adopted,” but data were collected via an online questionnaire without describing any sampling frame, recruitment channels, strata, or allocation procedure. Please specify exactly how proportional sampling was implemented (what strata, how proportions were determined, how participants were reached, and how duplicates were prevented).

4. The sample profile strongly suggests selection bias and limited generalisability, and you should address this explicitly and (if possible) analytically: 81% female, 98% urban, and 77% graduates is unlikely to reflect the region’s adult population distribution, especially if the stated target population is all Al-Qassim residents. At minimum, acknowledge that the online recruitment likely over-represented educated urban women; ideally, compare key demographics to official population distributions and discuss implications for inference.

5. The eligibility criteria need tightening and justification: the requirement “psychologically stable” is vague, ethically sensitive, and not operationalised in an online survey context. Please remove it or define how it was assessed (and why it was necessary).

6. The questionnaire reliability reporting appears incorrect and must be corrected because it affects confidence in all results: you report Cronbach’s alpha as 0.08 and state it is acceptable, which would normally indicate extremely poor internal consistency. This is likely a typo (e.g., 0.80) or a misapplied statistic (alpha is not meaningful for mixed-domain checklists). Please (a) confirm the correct alpha value, (b) specify which items formed the scale used for alpha, and (c) report reliability separately for subscales if applicable.

7. The instrument description is incomplete for reproducibility: you describe a 64-item tool and cite appendices (Appendix B, Appendix D), but the manuscript should ensure the full questionnaire (Arabic and/or English) is provided in Supporting Information, with scoring rules and skip logic.

8. Several key percentages are hard to interpret because denominators are not always explicit, especially where responses are conditional or “select all that apply”: for example, storage location percentages appear to be among those reporting unused medicines, while other outcomes appear to be among all respondents. Please state denominators clearly in each table and in the text (e.g., “among those with unused medicines, n=612…”).

9. There is a major internal contradiction about who respondents think is responsible for public education: the Abstract states that 60% “denied that the responsible sector… should be pharmacies,” yet Table 3 lists pharmacies as a responsible sector selected by 60%, and the text under Figure 1 also states 60% consider pharmacies primary. This must be resolved by checking the exact wording/coding of the question and rewriting the Results and Abstract accordingly (e.g., was the item “pharmacies are responsible—yes/no,” or “which sectors are responsible—select all”?)

10. The statistical analysis plan needs improvement in three specific ways: (a) you rely heavily on chi-square tests with a large sample where small differences become “significant,” (b) you report weak effect sizes (e.g., ϕc≈0.1) but do not interpret them properly, and (c) you run many tests across many demographics without addressing multiple comparisons. Please focus interpretation on effect sizes and pre-specified hypotheses, and consider adjusting for multiple testing (or explicitly justify not doing so).

11. The tables reporting p-values and effect sizes are difficult to read and in places appear misformatted (e.g., split ϕc values across lines), and should be cleaned for readability and accuracy. Please ensure each cell clearly shows p-value and effect size, or separate them into two clean columns, and ensure the same effect size metric is used consistently (Cramér’s V is typical for r×c).

12. Several variable labels and text contain errors that affect clarity and should be corrected before review can focus on substance (examples include income band text “More than 5000 SR-1000SR,” repeated/duplicated sentences, and multiple grammar issues such as “which smoothing similar”). A thorough language edit is needed.

13. The Results presentation would be stronger if you add one consolidated summary table (or figure) that shows, at a minimum: prevalence of unused medicines, top storage locations, top disposal methods for unused/near-expiry/expired medicines, and awareness indicators, each with clear denominators and 95% confidence intervals. Right now results are scattered across multiple tables and narrative.

14. The interpretation of “refrigerator storage” needs more nuance: you report that 62% store unused medicines in the refrigerator, but you do not assess whether those medicines actually require refrigeration or whether refrigeration is appropriate (many medicines should not be refrigerated, and temperature control in domestic fridges varies). If you did not collect medicine type/formulation, acknowledge that you cannot judge appropriateness; if you did, stratify by “requires refrigeration” vs “does not.”

15. Several environmental/AMR claims are phrased too strongly relative to what this study can support: for example, the Introduction suggests improper disposal may “increase medication resistance,” and the Discussion expands to wide claims about worldwide harm and flushing guidance. Please keep causal language proportionate—this study measures knowledge and self-reported practices, not environmental contamination or AMR outcomes—and ensure all such claims are tightly referenced and accurately worded (e.g., “may contribute to antimicrobial selection pressure” rather than asserting it does).

16. The ethical procedures need slightly more detail for an online survey: you state ethics approval and informed consent, but please explain how consent was obtained online (checkbox, information sheet, ability to withdraw) and whether any personal identifiers were collected.

17. The manuscript should report missing data handling and data cleaning steps (e.g., whether incomplete questionnaires were excluded, how “Not sure” responses were handled in denominators, and whether any logic checks were applied), because this affects the validity of the reported percentages.

18. The conclusion and recommendations should be made more specific and actionable: you recommend “regulatory guidelines” and “awareness,” but the paper can do better by translating the findings into concrete interventions (e.g., pharmacy-based take-back pilots in Qassim, standardized patient-facing disposal instructions at dispensing, national guidance on what should/should not be flushed, and evaluation plans). This can be tied directly to the large proportion reporting disposal in household bins and low formal education exposure.

19 The limitations section is on the right track but should explicitly list the biggest threats to validity in this study: convenience online sampling, non-representative demographics, self-report and social desirability bias, inability to establish temporality/causality, and inability to verify actual disposal behaviors.

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Reviewer #1: No

Reviewer #2: Yes: Yusuff Adebayo Adebisi

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-->PONE-D-25-52812R1-->-->Addressing the Disposal of Unused and Expired Medications in Saudi Households: Time to bridge the regulatory gaps-->-->PLOS One

Dear Dr. Abdulsalim,

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.-->--> -->-->1. Please respond to the journal requirement comment, particularly figure copyright issue raised during the first round revision-->-->2. Provide line number in to your manuscript. -->-->3. In your point-by-point response, add page number and line number to indicate where the change was made in the revised manuscript.

Please submit your revised manuscript by May 12 2026 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 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.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only  the individual author can complete the verification step; PLOS staff cannot  verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Dawit Getachew Gebeyehu, MPH

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

Dear Authors, thank you for your efforts to address the reviewer's concern; however, please include the page and line number where this change was made. Also, please address journal requirements, ensure that they are included in your point-by-point response, and upload them separately as pdfs.

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To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

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Addressing the Disposal of Unused and Expired Medications in Saudi Households: Time to bridge the regulatory gaps

PONE-D-25-52812R2

Dear Dr. Abdusalim,

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,

Dawit Getachew Gebeyehu

Academic Editor

PLOS One