PONE-D-19-30086

Factors Affecting National Medicines Regulatory Authorities Financial Sustainability –The East African Community Case Study

PLOS ONE

Dear Professor Kaale,

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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: N/A

Reviewer #2: I Don't Know

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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

Reviewer #2: Yes

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

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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: The article covers an important component of the regulatory systems and the conceptual approach to the topic is sound and holds practical relevance to not only African States but to many LMICs. However, few points are identified here which need attention to improve the understanding of the study findings and increase clarity.

Overall Gaps:

Inconsistent use of terms like TFDA and TMDA being used interchangeably throughout the document.

Methodology: The method being mixed method approach has a quantitative and qualitative component of data. However, the number of respondents for each country and their general demographic detail (age, gender, qualification, experience of working, level of engagement with NMRA etc.), an interview or meeting guide need to be shared to support study methodology. The source of primary data collection (e.g, official notifications, reports, webpage of the NMRA etc) is missing (see Page 5, line 105-106). It seems that the review of NMP was a component of methodology as discussed latter in results (subheading 1) but needs to be mentioned here with the sources accessed for retrieving data on funds and policies. The exchange rate applied needs to be mentioned properly “prevailing average annual USD currency exchange rate” is insufficient to serve the purpose.

Results:

Subheading 1

Page 6, line 127-128: Is the financial autonomy laid down in the NMP (please mention clearly)

Subheading 2

Page 7, line 129-131: Needs clear representation of data to support this. It will be nice to adda table with description of each country’s information under financiall autonomy status (Y/N), if Y since (year), under law or rule (State the rule/act or law reference), year of passing and enactment of law.

Subheading 3

Page 7, line 142-144: The figure represents the annual trend only so it can be described in a separately.

Subheading 4

Page 8, line 166: PPA (Please expand abbreviation on first use)

Page 8, line 167-170: Please rephrase to more concise .... 73.20% and 98.25%, respectively over the reported duration

Page 9, line 178-182: It will be nicer to mention the funding agencies contributing up to a certain amount limit or above it for each country to make it more quantifiable to relate to the figure 4.

Subheading 5

Page 9, line 192: PPB ??

Page, line 194-195. Addition of a figure on annual trend need will make the results more clear nd understandable.

Page 9, line 196-200: The point can be shifted to limitations of the study. Moreover, what could have been easily added is the population size and the year wise and/or country wise HR strength of the technical and nontechnical personnel in the NMRA as something that can explain the expenditure.

Discussion

Reference 6 is closely related to the objective and design of the study and is recommended to be discussed the results of the study.

Page 10, line 218: Reference 7 is unpublished, Authors should try to used published references for the details discussed here (references for improved regulatory systems in the countries under study for the study period)

Conclusion:

Lapses in timely release of funds is not mentioned in the results nor data extraction from the interviews or meetings was disclosed in the article which could support this conclusion. Results need to be more explicit to support qualitative segment.

References:

Reference formatting needs attention for uniform style.

Reviewer #2: 1. Insufficient detail on methods – how was data analyzed?

E.g. NMPs- was there a document analysis?

2. Are the NMP stipulations legally binding? The discussion indicates this, but it is not clear.

3. Line 146- 148 says each budget approx. doubled, but it is difficult to discern this about the ZFDA in Fig. 1. Suggest editing figure to include smaller intervals on Y axis.

4. Throughout the paper, “N” is used to denote a USD amount. Please double check whether the use is correct, as I am not familiar with the use of N for a dollar amount (rather only for total population or sample).

5. It should be noted why there is no data for Kenya and Rwanda for Fig. 2.

6. Can the scale for Fig. 3 also be changed to capture the low amounts better?

7. While donor contributions to NMRAs may vary, it would be interesting to know which of the donors provided the most funding, per country and perhaps overall.

8. Fig. 4- It looks as though the SDs are negative. I am not a statistician, but I do not think that’s possible? Suggest a basic statistical review and/or make this more clear in the figure.

9. Line 217- Please spell out QMS and IMS.

10. Please review the grammar in the discussion.

11. Line 242- use of the word “dispose” seems awkward, consider alternative such as “use the revenue”.

12. In lieu of pharmaceutical market size data, one could possibly show, as some kind of possible indication of market size perhaps, the number of medicines listed on the national essential medicines lists. This data is available here: https://global.essentialmeds.org/dashboard/countries

If used, this publication can be cited for the source:

Persaud, N., Jiang, M., Shaikh, R., Bali, A., Oronsaye, E., Woods, H., & al., e. (2019). Similarities and Differences in Essential Medicines Lists of 137 Countries: a quantitative analysis. . Bull World Health Organ.

13. In the discussion, the need for government investment is noted, but I think the opportunities to collect revenue from industry should also be stated as a key source again. Given the projections in market expansion, it seems only fair that industry should not only profit but also be contributing to NMRA activities from which they will ultimately benefit.

14. State opportunities with the African Medicines Regulatory Authority?

15. It seems that paragraph lines 277-284 should be in the discussion rather than conclusion (see comment above on industry funding in discussion). This is too much detail for the conclusion.

16. References require proper formatting.

17. Are there more references to cite on effectiveness of regulatory harmonization?

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Reviewer #1: No

Reviewer #2: No

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PONE-D-19-30086R1

National Medicines Regulatory Authorities Financial Sustainability –The East African Community Case Study

PLOS ONE

Dear Dr Kaale,

Thank you for re-submitting your manuscript to PLOS ONE. This has now been reviewed and we have received advice from both reviewers. Both reviewers have indicated that you have made good progress with the amended version of your manuscript. One of the reviewers have raised a number of issues - we feel if you can address these  the paper should be able to be published by PLOS ONE. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the latest review process.

We would appreciate receiving your revised manuscript by Jun 28 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Eduard J Beck, PhD, FAFPHM, FFPH, FRCP

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 #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: 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: No

**********

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: Overall the quality has improved, although it still requires more detail to properly understand steps taken to conduct this study and therefore to evaluate the validity of the findings. I think the discussion is very interesting now!

1. While the title indicates that a case study methodology was used, the methods section does not. In my view the study did not take a case study approach (which is a methodology to intensively study a case for the purpose of understanding a larger population). I suggest to remove case study from the title as it may be misleading and replace it with something like “National Medicines Regulatory Authorities Financial Sustainability in The East African Community”.

2. Abstract Methodology: incorrect use of semi-colon, replace with commas. This is also the case on lines 62-64, 116-119 and a few more throughout the manuscript.

3. Line 99: Reconsider case study use here, consider alternative wording (as per my comment 1).

4. Whether semi-structured interviews were done and how is unclear, as there is no detailed information on participants or data collection in this regard. S1 indicates that respondents completed the questionnaire form on their own or perhaps it was administered by the study team? It appears that a descriptive analysis was done from a questionnaire, but it’s hard to tell. If interviews were done, this requires a lot more detail, such as:

- Was a topic guide used for the semi-structured interviews or was it based directly on the questionnaire (and thus perhaps not really semi-structured)?

- How were participants selected, how many participants responded, what was the length and format of the interviews?

- Were these audio-recorded and transcribed? How was data analyzed (more information so I could reproduce this)?

- How was sampling conducted?

5. In any case, it would help to have more participant information. Were participants all the heads of NMRAs participants and M&E experts (i.e. did all agree in each of the countries?), how many respondents were there total? Why were these specifically selected?

6. Lines 108-109: In the follow-up visits, who provided the missing data at the agencies and who validated the data? How exactly was the data validated (e.g. official records)? Or how do you know it is reliable? Were these different respondents than the initial interviews?

7. Related, where was the budget data obtained from specifically (official records, or did you rely on responses from individuals) and how was it validated if it was through responses?

8. How was the questionnaire/ data collection tool developed? Detail is needed to understand what it is based on (any previously used standardized tools?) and its validity.

9. Line 230-232: Why is this the assumption? Can you be more explicit?

10. Line 234 (and throughout the manuscript): Check capitalizations, as these are inconsistent in some parts of the paper. I also think there is a typo here with “multi-county” instead of “multi-country”.

11. Line 240: pluralize sound government policies and legal frameworks?

12. Line 247: typo with t before government?

13. Line 271: “chronic lifestyle diseases” implies the conditions are a result solely of individual behaviours which is shown to be generally not true, suggest changing to non-communicable diseases or simply chronic conditions

14. Line 314: “in particular” isn’t necessary here

15. PREVIOUS COMMENT

Reviewer 2 Comment

Throughout the paper, “N” is used to denote a USD amount. Please double check whether the use is correct, as I am not familiar with the use of N for a dollar amount (rather only for total population or sample).

Author’s response

Deleted ‘N’ associated with $ sign and replaced the dollar sign with USD throughout the text Throughout the text

REVIEWER REPLY: One ‘N’ was not deleted/missed on page 9.

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Reviewer #1: No

Reviewer #2: No

[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 to be viewed.]

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National Medicines Regulatory Authorities Financial Sustainability –The East African Community Case Study

PONE-D-19-30086R2

Dear Dr Eliangiringa A. Kaale

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,

Helen Schneider, MBChB, MMed, PhD

Academic Editor

PLOS ONE

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