PONE-D-19-20413

Availability, prices and affordability of essential medicines for treatment of diabetes and hypertension in the private sector in Zambia.

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Khin Thet Wai, MBBS, MPH, MA (Population & Family Planning Resear

Academic Editor

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Additional Editor Comments (if provided):

This paper used the WHO standardized methodology and could be able to bring out the policy-related evidence to improve access to antidiabetics and antihypertensive in the private sector at Zambia.

The significant difference median price ratios for LPG between the study sites requires an appropriate statistical test.

Apart from that authors should respond thoroughly to the modest request of reviewers to deal with sampling issues, some results and the discussion part to improve the writeup.

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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?

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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: Line 31: "In line with its pledge to achieve Universal Health Coverage by 2030, the government..". The authors have to indicate the country as this is the first statement in the introduction.

Line 121-122: "To verify effectiveness of the data collection approach and accuracy of the tool, local pilot surveys were conducted at two pharmacies in Lusaka". Was this data included in the final analysis for this paper?

Line 197-199: "Of the 32 selected medicines, 12 had no OBP registered with ZAMRA. The survey drugs thus

198 comprised 14 OBPs (Diabetes: 6; Hypertension: 8) and 32 LPGs (Diabetes: 7; Hypertension:

199 25)." The number of OBP (12 + 14) does not match with LPG (32). Is there an explanation for this?

Line 240: "Table 3. Median price ratios (interquartile ranges) of surveyed drugs." Preference would be to include the results of Central province in the same table than text below it.

Line 259: "Affordability." The authors could have used the minimum wage for Zambia than the 'national absolute poverty line' as the study was conducted in major cities where majority of the individuals are employed in various sectors.

Reviewer #2: GENERAL COMMENTS:

The paper explored an important subject of availability, pricing and affordability of antidiabetic and antihypertensive medicines in the private sector in Zambia. Addressing treatment challenges for non-communicable diseases in low-middle income countries does require evidence to inform policy and practice interventions towards the universal goals of ensuring access to essential medicines. Though the paper was limited in scope and coverage in terms of study sites, a country-wide study would add value to the findings providing insight into the magnitude of the medicine availability for diabetes mellitus and hypertension treatment in Zambia’s private sector. Overall, the paper is relevant, well structured, has sufficient scholarly rigor, and has a logical flow of arguments, notwithstanding the limitations highlighted by authors.

SPECIFIC COMMENTS:

The title is a bit misleading. Reading through the paper, the scope of population coverage was rather limited. The paper only focussed on measuring availability, pricing and affordability in the private pharmacies in Zambia, which does not necessarily represent the entire scope of private sector providers of medicines. I note that the study did not cover the other private sector providers such as private hospitals and consulting room dispensaries. I assume these private players also do provide antidiabetic and antihypertensive medicines in the setting (Zambia)? Since the coverage of study sites was limited, I can suggest the authors revise and refocus their title to state “…availability, price and affordability in the private pharmacies in Zambia”

Line 4: It is good that the authors sampled the pharmacies from the list of registered (legal) outlets, however, among the 99 private pharmacies surveyed, the authors do not state the distribution of these pharmacies in the setting, whether and how many of these pharmacies were located in urban versus rural areas of Zambia? Did availability, pricing and affordability vary by location of the pharmacy in the setting?

Line 7: Regarding reasons why “international reference pricing” was used as a measure of affordability, did the authors consider difference in pricing considerations of originator brand products, local brands, versus ‘generic’ products, including cost variations between European versus Asian manufactured products on the market? Was there a local costing structure for medicines in Zambia? I will appreciate a comment on that.

Line 13: In the results section, a bit more clarity required when stating the findings. Some missing words and stylistic aspects in the opening sentence e.g. opening a sentence with a numeral?

Line 14: Authors state: “availability levels for the remainder …..”, but what is the remainder in this case? How many medicines were the remainder? The sentence is not clear. Consider using absolute measures.

Line 31: Which “government” are authors referring to? The opening paragraph (Line 31 to 35) needs to be recast and context provided.

Authors seem to be using the terms “drug” and “medicine” interchangeably? I highly doubt that the two terms are synonyms. I can suggest authors maintain to use one term consistently throughout the paper.

Line 38: Did the authors select the three provinces conveniently or purposively? This is not clear and if so, why? If not, a statement should be provided how authors ensured selection bias of provinces was avoided.

Line 98 – 100: Was a sample size formula applied to select the 99 pharmacies from the total population of private pharmacies? If so, what were the assumptions forwarded in the computation of sample size (notwithstanding the methods developed by Measure Evaluation)?

Moreover, how was the site selection (private pharmacy) done? Was due consideration given to systematically or randomly select the pharmacies or otherwise? A clear statement on this will be appreciated.

Line 103 – 104: How did the authors arrive at 10% for adjusting sample size? Any explanation or justification for this? Why 10% and not say 15% or 20%? What was the considered assumption for non-response rate?

Line 108: Among the medicines that consisted the 7 antidiabetic and 25 antihypertensive medicines, it is not clear whether authors were only interested in the single formulation medicines, or even co-formulated products?

It is a shame that if indeed the medicine was not available (perhaps stocked out) at the respective pharmacies on spot survey at time of data collection, the data collection tool would have also done well to collect data on whether the medicine was ever stocked, the number of stock-out days in a period specified, and so on. This finding could potentially inform whether there were underlying issues with medicine demand or supply challenges in Zambia. I feel readers of this paper would also be interested to know this information.

Line 145 - 147: The measure of availability that was used by Authors was rather unreliable, despite the method being widely applied by previous studies. There is a difference in ‘on the spot availability’ and ‘consistent availability’. It appears to me the authors measured ‘on the spot availability or presence’ of the medicines on spot survey. Assessing availability of medicines, in the context of pharmaceutical supply chain management principles, requires measuring commodity security i.e. consistency of availability to maintain steady flow of the product to majority consumers at all times. A medicine must be in stock in sufficient quantities to meet demand for a specified period of time consistently to date (without stock out) for it to be deemed available. Was commodity security of supply a consideration or on the spot availability of the product on the shelf?

Line 167: “STC” should be written in full when first used, then abbreviated thereafter.

Line 177: The subheading sounds repetitive of the two previous subheadings used. I feel this section from line 177 to 182 is not adding any value to the paper. If the information is needed, authors can take move the sentences to other sections.

Line 223: Am wondering if private pharmacies in the setting not having available some of the medicines surveyed is a surprising finding. Am not surprised by this finding since ideally, most if not all these antidiabetic and antihypertensive medicines are supplied on prescription-only basis to clients accessing private healthcare. In the private (for-profit) sector, commodity availability is often driven by demand (from prescriptions being received at the private pharmacy). Therefore, we wouldn’t expect a particular medicine that is not frequently prescribed to be so available in all the private pharmacies, more especially if that medicine is not on the EML or national standard treatment guideline (STG) for diabetes or hypertension. In actual fact, to be prescribed that often the medicine has to be at least the choice specified by the national treatment guidelines thereof. Did the authors consider this possible cause negatively impacting on availability in the pharmacies? So to avoid distorting the availability picture, Authors would do well to focus on those medicines that actually have marketing authorisation and feature on the National Formulary and/or STG rather than the WHO lists as reference of what is actually recommended to be prescribed for diabetes and hypertension treatment in Zambia. A discussion point perhaps?

The findings show that even some medicines without official marketing authorisation were actually selling at a price in the private pharmacies in Zambia. If some of the pharmacies were actually stocking and selling antidiabetic and antihypertensive medicines that had no official marketing authorisation from the regulator, did that imply there was illegal sale and distribution of some antidiabetic and antihypertensive medicines in private pharmacies in Zambia? Was that a weakness in the regulatory aspects? Do you want to comment on that?

Line 270: Regarding pricing affordability for generic brands, I feel the findings in table 4 would be better interpreted when the actual average price paid per unit of sale is shown (whether per pack, number of tablets, or monthly supply quoted either in local or US dollar currency equivalent) and also the affordability index (using mean per capita income) indicated in the table 4.

Line 335, 427 and elsewhere: In the discussion, Authors bring out what appears to be some qualitative findings from informant responses (e.g. from Pharmacy managers about “varying delivery times” and so on). If at all there was a qualitative component in the study, why were the qualitative findings/results? Did the data collection also involve qualitative data? Were there any qualitative findings in the study? This needs to be clarified from the onset.

Line 447 – 460: Authors bring out a number of important limitations of the study. They can also do well to mention how these limitations were addressed or can be mitigated in future studies.

Line 462 – 471: The conclusion needs to be recast. Line 462 to 464 are not adding value to the section. Rather than general statements, authors will do well to address the research objective(s) by mentioning the overarching findings of the study.

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Reviewer #1: Yes: Felix Khuluza, PhD

Reviewer #2: Yes: Aubrey Chichonyi Kalungia

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Availability, prices and affordability of essential medicines for treatment of diabetes and hypertension in private pharmacies in Zambia.

PONE-D-19-20413R1

Dear Dr. Forsberg,

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With kind regards,

Khin Thet Wai, MBBS, MPH, MA (Population & Family Planning Resear

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All comments of reviewers are fully addressed.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #1: 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

**********

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

Reviewer #1: Yes

**********

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

**********

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

**********

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 comments. In addition, the authors have provided explanations where changes to my suggestions could not be taken on board.

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Reviewer #1: Yes: Dr. Felix Khuluza