PONE-D-25-43693

The Need for Patient-Centric Medicine Design: Investigating Key Physical Characteristics of Oral Solid Medications to Improve Acceptance of Elderly Patients in Addis Ababa, Ethiopia.

PLOS ONE

Dear Dr. Assefa,

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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Reviewers' comments:

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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

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

Reviewer #1: No

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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: No

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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

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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 research conducted by authors through analyzing questionnaire data from elderly outpatients attending outpatients clinics in 5 major hospitals in the capital of Ethiopia. The knowledge gap is the lack of data on medication characteristics preference of orals solid dosage forms. This aims to provide recommendation to pharmaceutical industry manufacturing especially generic drugs for those used commonly by this population. The main outcome was acceptance evaluated by a questionnaire score.

The authors conducted a thorough analyses of all the possible patient-related factors as well as drug-related factors that impacted the acceptance. However, the main independent variables include drug-related characteristics (e.g., size, shape), while patient-related factors (e.g., hypertension, polypharmacy) also showed significant associations with acceptance.

The analysis provides important, though largely expected, insights into factors influencing acceptance of oral solid dosage forms among elderly patients. However, patient-related characteristics such as hypertension and polypharmacy were also found to be significantly associated with acceptance and may act as confounders in the observed relationships between drug characteristics and acceptance. If the goal is to determine how drug characteristics influence acceptance, independent of patient characteristics, then adjustment for patient factors is essential.

Reanalyzing the data using a multivariable logistic regression model that adjusts for relevant patient-level covariates should be included presenting both unadjusted and adjusted results.

The results table #6 presents both Crude (COR) and Adjusted Odds Ratios (AOR). However, the Methods section does not describe how the adjusted model was constructed or which covariates were included in the adjustment. It is unclear what was adjusted for, what reported AORs represent or how potential confounding was handled. Which variables were entered into the multivariable logistic regression and the rationale for their inclusion (prior evidence, p-value threshold, or theoretical relevance?).

I recommend to clearly describe the modeling approach and adjustment procedure, and to ensure that the variables reported as “adjusted” in the table correspond to the specified model in the Methods.

Limit the use of abbreviations which are not frequently used or standardized. Explain Abbreviations and add statistical test in the footnote of tables. Remove “2025” from the title of tables..etc

Abstract

• Mention the knowledge gap in the.

• Clarify in the abstract the type of data analysed i.e. medication-related, patient-related, acceptance, questionnaire,..etc

• Mention the type of statistical tests applied

Methods:Details about sample size calculation and sampling technique could be moved to the suppl. Material.

Results:

Age distribution with min and max to present in the demographic table.

No supporting information is available. Provide the applied questionnaire as suppl. Material.

Discussion

The results are largely expected, could the authors discuss what their study add to the existing literature or which particular aspects were deduced regarding the setting in a low-middle income/resource country?

For the problematic dosage forms, were there other alternatives on the market that were easier to swallow e.g. smaller or dispersible, that the physician may prescribe?

Were there any results describing patient experience with powders? Soft gelatine capsules? To be discussed. How was the OSDF distribution?

The results of the study regarding the size and coating should also be discussed in light of the feasibility and limitations of the pharmaceutical manufacturing process. The authors should acknowledge in their discussion not only patient preferences but also constrains by manufacturing feasibility such as dose load, coating materials, compression strength ..etc.

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Reviewer #1: No

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PONE-D-25-43693R1

The Need for Patient-Centric Medicine Design: Investigating Key Physical Characteristics of Oral Solid Medications to Improve Acceptance of Elderly Patients in Addis Ababa, Ethiopia.

PLOS One

Dear Dr. Assefa,

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.

The revised manuscript has been further assessed and the comments from the reviewers can be found below. Please review their reports and make the appropriate revisions to address any concerns raised.

Please submit your revised manuscript by Feb 21 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.

We look forward to receiving your revised manuscript.

Kind regards,

Emma Campbell, Ph.D

Staff 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.

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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 #1: All comments have been addressed

Reviewer #2: (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 #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: No

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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

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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: Thanks for undertaking the changes to improve the content and address the issues observed. No further comments

Reviewer #2: Dear authors,

Thanks for conducting this questionnaire based study in Ethiopia to assess factors impacting the acceptability of solid oral dosage forms in older adults in your country.

First of all I would like to comment on the term “elderly patients”. People working in the field strongly recommend avoiding to use the term “elderly” see Murphy, E., Fallon, A., Dukelow, T. et al. Don’t call me elderly: a review of medical journals’ use of ageist literature. Eur Geriatr Med 13, 1007–1009 (2022). https://doi.org/10.1007/s41999-022-00650-4 as reference. Instead you might want to use the term older adult consequently in your manuscript.

Introduction

Acceptability is an overarching term used to describe a patient's ability and willingness to take the medication as intended, and/or the willingness of a lay care giver to administer the medication. It covers a range of aspects such as palatability, swallowability, handling,...Please be more specific in the introduction which aspects were assessed in the questionnaire and summarized under the term acceptability. Please also explain more clearly why you expect that the results in Ethiopia differ from those reported for Europe.

Method and Materials

Your patient population is not clearly enough described. As a reader you don't know if the public hospitals included in the study are specialized in certain indications or offer the full range of services. From my perspective this is important to understand the results obtained.

Furthermore, the term “chronically” should have been more clearly defined, e.g. taking the medication for at least X months.

Equations presented. Please check and align the use of capital letters (d and D). The second equation is not well described. Personally I already understood the sentence “The total sample size (n = 422) was proportionally allocated to each hospital…”

What exactly do you mean by “Eligible participants …, based on patient discharge order.”?

I assume the senior academic staff translating the questionnaire back to English “were not aware of the original questionnaire” (typo).

It is also unclear what you mean by “...those who held some of his/her medicine, and those who

were volunteers,...”?

What do you mean by “A maximum of 5 oral solid medications were taken from the elderly patients, which can cover more than 90 percent of their medications.”?

Variables of the study

Have you checked that those variables, which you call independent, are not correlated to each other? For instance, education, income and residence or certain symptoms and diseases.

Operational definition of terms

The terminology used in the text here, e.g. palatability is not used in the questionnaire itself. Did you use taste and other aspects to come up with a palatability score? If yes, how was this done?

Results and discussions

Avoid use of abbreviations in titles (OSM)

Figure 1: How representative is your study population compared to the population in Ethiopia in the same age range?

Table 1: I assume you mean “ Waaqeffannaa” and not “wake feta”.

The terms in the questionnaire are often not clearly defined, such as swallowability difficulties, visual impairment, …Furthermore, looking at the questionnaire and the results I wonder how you managed in multimorbid patients using polypharmacy to distinguish if the amount of medications are attributed purely to the disease. Please explain how you did this, e.g. “Among the disease conditions affecting elderly patients, hypertension emerged as the most common (43.1%) with 50.2% of oral solid medication usage, followed by other cardiac-related disorders and diabetes mellitus.”

Table 4 looks incomplete in the last column.

How was the taste assessed? How reliable is the result communicated based on that?

Table 5 mentioned “bitter color” as taste and “partial score line”. What is meant here?

How was the judgement on the labelling performed? Was language taken into account?

From a methodological point of view I have some issues understanding based on the questionnaire, how the column acceptance of medication in table 6 was derived. It seems like “acceptance” yes or no is a value related to the patient and not the medicine he/she takes.

This makes it difficult to understand the conclusions made such as the score lines are better accepted than tablets without. Might be an effect of reimbursement (prescribing a higher dose strengths) and asking the patient to split medication. In this context you should discuss dosing errors etc.

In the discussion you mention limitations of medications in Ethiopia, e,g. Not available in a different format (dispersible, with score line, …). Are those medications available in a different format in other countries / elsewhere?

Looking at the questionnaire itself it would have offered other important insights into dosing frequency, easy to take (with/without food),...Unfortunately those aspects are not mentioned in the article.

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Reviewer #1: No

Reviewer #2: No

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The Need for Patient-Centric Medicine Design: Investigating Key Physical Characteristics of Oral Solid Medications to Improve Acceptance of Elderly Patients in Addis Ababa, Ethiopia.

PONE-D-25-43693R2

Dear Dr. Assefa,

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.

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Kind regards,

James Mockridge

Staff Editor

PLOS One

Additional Editor Comments (optional):

Title and abstract in the submission system: Although you have updated the manuscript to change ‘elderly’ to ‘older’ in response to the reviewer's comments, please ensure that you have also updated the title and abstract in the submission system accordingly. Currently 'elderly' is still being used and this needs to be changed to 'older'.

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

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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

**********

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

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

**********

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

**********

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)

Reviewer #2: Dear authors,

thanks for up-dating the manuscript and also taking care for avoiding the term "elderly". It would be nice of this term could be replaced in the title as well.

Thanks

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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.

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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

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