Availability and Affordability of Medicines for Diabetes and Cardiovascular Disease across Countries: Information Learned from the Prospective Urban Rural Epidemiological Study
Round 1
Reviewer 1 Report
Nguyen et al. prepared a commentary based on the findings from a Prospective Urban Rural Epidemiological (PURE) study they published earlier. The conclusions are important (improving access to medicines for cardio-metabolic diseases should be a key part of the strategy to lower the burden of CVD globally), but the novelty seems to be compromised due to the findings being obvious (LICs and MICs have seen a low availability and affordability). The English usage of this manuscript is clear and professional, while some improvements could be made on the Figures:
(1) Keywords are missing.
(2) Figure 1: the data for Zimbabwe is an obvious outlier. Maybe the authors could consider briefly describing the situation of Zimbabwe in the main text or Figure 1 caption (what is the sample size for Zimbabwe and is the data reliable for Zimbabwe?).
(3) Figure 1: it would be nice to provide axis labels.
(4) Please spell out the abbreviation “OR” (odds ratio) to help readers who are less familiar with statistics better understand this manuscript.
(5) The authors may consider increasing the font size of the axis labels of Figures 1 and 2, as well as increasing the resolution of the Figures.
(6) Since the section “Availability, affordability, and consumption of fruits and vegetables” seems a bit off-topic (the commentary is primarily about medicines), it would be nice to add citations to the following sentences: “In addition to essential medicines, adequate consumption of fruits and vegetables are beneficial for cardiometabolic health. According to most nutritional guidelines, consumption of at least two servings of fruits and three servings of vegetables per day was recommended”.
Author Response
Nguyen et al. prepared a commentary based on the findings from a Prospective Urban Rural Epidemiological (PURE) study they published earlier. The conclusions are important (improving access to medicines for cardio-metabolic diseases should be a key part of the strategy to lower the burden of CVD globally), but the novelty seems to be compromised due to the findings being obvious (LICs and MICs have seen a low availability and affordability). The English usage of this manuscript is clear and professional, while some improvements could be made on the Figures:
(1) Keywords are missing.
Response: We have provided the keywords (cardio-metabolic health; diabetes; cardiovascular disease; essential medicines; availability; affordability; global health)
(2) Figure 1: the data for Zimbabwe is an obvious outlier. Maybe the authors could consider briefly describing the situation of Zimbabwe in the main text or Figure 1 caption (what is the sample size for Zimbabwe and is the data reliable for Zimbabwe?).
Response: Data from Zimbabwe is reliable. There were 808 participants with high cardiovascular risk from Zimbabwe.
(3) Figure 1: it would be nice to provide axis labels.
Response: We have added the y axis label.
(4) Please spell out the abbreviation “OR” (odds ratio) to help readers who are less familiar with statistics better understand this manuscript.
Response: We have changed “OR” to “odds ratio”.
(5) The authors may consider increasing the font size of the axis labels of Figures 1 and 2, as well as increasing the resolution of the Figures.
Response: We have edited the figures as suggested.
(6) Since the section “Availability, affordability, and consumption of fruits and vegetables” seems a bit off-topic (the commentary is primarily about medicines), it would be nice to add citations to the following sentences: “In addition to essential medicines, adequate consumption of fruits and vegetables are beneficial for cardiometabolic health. According to most nutritional guidelines, consumption of at least two servings of fruits and three servings of vegetables per day was recommended”.
Response: We have added references.
Reviewer 2 Report
The authors (Nguyen TN et al.) of the manuscript « Availability and affordability of medicines for diabetes and 2 cardiovascular disease across countries: learnings from the Prospective Urban Rural Epidemiological Study » produced a commentary on the PURE study. This epidemiological study used a prospective cohort of 202,072 people aged 35-70 years from 27 high, middle, and low income countries across 6 geographical regions. The article presents only 2 figures.
The new results could come from the two figures. The figure 1 presents the percentages of PURE participants with high cardiovascular risk from communities where three types of essential cardiovascular medicines are available and affordable. The figure 2 presents the availability of these three drug types was consistently lower in LICs compared with countries with higher income.
The conclusion is to recommend access to medicines for cardio-metabolic diseases for low income countries
The criteria for this epidemiological study have not been presented in a summary, as well the list of countries and the levels of high to low incomes. The criteria from urban to rural may be difficult to apply for country comparison. I would appreciated that a real discussion on all the biais that would affect the PURE study despite many medical reports and a table presenting the recults of similar design.
The figure 1 is not understandable : no legend is found as well as the percentage is not indicated and the histogram legends not defined.
The figure 2 did not mention how is calculated the all 3 types as the histograms in function of income are similar to statin graph whereas a full access (>90 %) to hypertensive drugs is presented on the left of the panel. These figures add little to the previous results of the PURE study.Access to Western medicines seems to me to be a reductive way of thinking. How can we consider that traditional medicines such as Ayurveda (India) or specific Chinese medicines exist in India or China for example? Are the causes of Western cardiometabolic diseases the same from one country to another? The translation of evidence-based medicine to low-income countries was not discussed in this commentary.
Why did you choose a panel of 35- to 70-year-olds? Is there a gender influence?
The evidence was based on disease-associated mortality and hospitalizations, primarily through randomized controlled trials for antihypertensive drugs and statins. Many questions remain unanswered, such as nutrition (obesity in Western countries and overeating) or environmental factors (physical exercise). One of them is the distance to the hospital for heart attacks and strokes. Hospital density and proximity could be a criterion for high versus low income. What are the limitations of the PURE study?
Author Response
The authors (Nguyen TN et al.) of the manuscript « Availability and affordability of medicines for diabetes and 2 cardiovascular disease across countries: learnings from the Prospective Urban Rural Epidemiological Study » produced a commentary on the PURE study. This epidemiological study used a prospective cohort of 202,072 people aged 35-70 years from 27 high, middle, and low income countries across 6 geographical regions. The article presents only 2 figures.
The new results could come from the two figures. The figure 1 presents the percentages of PURE participants with high cardiovascular risk from communities where three types of essential cardiovascular medicines are available and affordable. The figure 2 presents the availability of these three drug types was consistently lower in LICs compared with countries with higher income.
The conclusion is to recommend access to medicines for cardio-metabolic diseases for low income countries
The criteria for this epidemiological study have not been presented in a summary, as well the list of countries and the levels of high to low incomes. The criteria from urban to rural may be difficult to apply for country comparison. I would appreciate that a real discussion on all the bias that would affect the PURE study despite many medical reports and a table presenting the results of similar design.
Response: We have provided more details on Page 4.
The figure 1 is not understandable : no legend is found as well as the percentage is not indicated and the histogram legends not defined.
Response: We have edited Figure 1.
The figure 2 did not mention how is calculated the all 3 types as the histograms in function of income are similar to statin graph whereas a full access (>90 %) to hypertensive drugs is presented on the left of the panel. These figures add little to the previous results of the PURE study.Access to Western medicines seems to me to be a reductive way of thinking. How can we consider that traditional medicines such as Ayurveda (India) or specific Chinese medicines exist in India or China for example? Are the causes of Western cardiometabolic diseases the same from one country to another? The translation of evidence-based medicine to low-income countries was not discussed in this commentary.
Response: We have added the axis label for Figure 2. The discussion about traditional medicines is out of the scope of this article.
Why did you choose a panel of 35- to 70-year-olds? Is there a gender influence?
Response: This was in the original study which was focused on examining populations for the determinants of cardiovascular disease. The age group was similar to other large scale surveillance studies looking at cardiovascular risk, eg. NHANES https://www.cdc.gov/nchs/nhanes/index.htm
There is much research on gender differences in cardiovascular health, for example one paper directly from PURE https://doi.org/10.1016/S0140-6736(20)30543-2 We were uncertain what the specific question about gender was here, but gender was not a main focus of this paper.
The evidence was based on disease-associated mortality and hospitalizations, primarily through randomized controlled trials for antihypertensive drugs and statins. Many questions remain unanswered, such as nutrition (obesity in Western countries and overeating) or environmental factors (physical exercise). One of them is the distance to the hospital for heart attacks and strokes. Hospital density and proximity could be a criterion for high versus low income. What are the limitations of the PURE study?
Response:
The limitations of the PURE study has been discussed in many previous publications. The relationship between contextual variables such as access to medicines and access to health care and health outcomes is complex. PURE has captured some data with respect to availability and affordability of medications and some data on available health services and types, but the data collection was limited by resources. As such a detailed examination of the health system, e.g. systematic examination of all health care providers and hospitals, all sites that dispense medications was not able to be done.
In terms of affordability of medicines, the PURE results capture only part of the costs of treatment, other costs such as professional fees or travel or time taken of work to visit a doctor were not taken into account and hence, affordability could have been overestimated. In addition, there are policies and other activities of non-governmental organisations in various regions of the world that may provide free medications to some participants in some countries, which may influence medication use and access to variable degrees. We do not have information about how household incomes might have changed during follow up, which may be important given the economic impact of illness. Also, availability and affordability were only assessed at baseline (but this is inevitable in such a large study in which we aimed to relate these to long-term outcomes) and may have changed over time. Moreover, during the study time, several countries transitioned to other income categories, for example, India: LIC – LMIC (2009), China: LMIC – UMIC (2013), Colombia: LMIC – UMIC (2008), Iran: LMIC – UMIC (2010). Along with these transitions, their health systems may have changed as well. The availability and affordability of medicines were assessed at the community pharmacy level, therefore it may not necessarily reflect the availability and affordability at different points of care such as pharmacies at public health facilities or private health facilities. While our method attempted to identify the most available medicine in the pharmacy and its cost, there is variation in availability and price particularly between generic and brand drugs across pharmacies. Availability of a particular CVD medicine may also depend whether the country Essential Medicine Lists include the medicines in the first place. In addition, there may be other aspects of access to health care that may have changed, such as number of health workers, availability of diagnostic and therapeutic interventions, etc. and we do not have data on these. The criteria used to define high risk patients resulted in having a mixed group of patients that are not at the same level of risk. For the various reasons described above, the hazard ratios calculated in these analyses could be underestimated compared to if availability and affordability could be more accurately measured.
Reviewer 3 Report
Please find comments attached.
Diabetology-1576802-peer-review-v1_02.01.2022
I am thankful for being given the opportunity to review this commentary titled “Availability and affordability of medicines for diabetes and cardiovascular disease across countries: learnings from the Prospective Urban Rural Epidemiological Study” by Nguyen et al. The authors are highly respected physician-scientists in the field. This commentary offers to consolidate the findings on the availability and the affordability of medicines for diabetes and CVD, extracted from several informative studies as part of the PURE trial. There are, however, some comments that I would like the authors to consider.
- Much of the information presented in this article seems to have been written from the perspective of a review rather than a “commentary”. All subsections are more-or-less the summary statistics from previously analyzed data of the PURE trial. The current article lacks the critical insightful thoughts/learning that mandates from a commentary. For example, most of these insights/commentaries are limited to lines 100-107 for section 1, lines 130-132 for section 2, lines 167-171 for section 3, lines 198-201 for section 4, with some unique critique limited to lines 242-257.
- It seems like the take home message from the four subsections is that - the low-income countries are the ones suffering the most when it comes to either the availability or the affordability of medications related to diabetes and CVD. This may not be as surprising as one would assume that a country’s economic status (income level) intrinsically links to an individual’s/community’s health condition, however, the PURE trial emphatically provides the statistics for it. It would be insightful if the authors could include their own perspectives, and those from their physician colleagues who have been involved in these studies (the multi-enter, multi-nation PURE trial), and how their experiences in handling such patients (stratified based on economic/income conditions) rope into this current “commentary” article. A more nuanced discussion/commentary focusing on multi-factorial aspects on the outcomes of the PURE trial in context of the current article is required.
- It has been a little more than 15 years since the PURE trial was initiated based on the World Bank’s stratification of a country’s economic status. Has this economic stratification changed in the current years, and are there any new studies that have altered the findings of the PURE trial as to what was observed from its data generated 15-17 years back?
- A table summarizing the key statistics for each section (including the associated references) would be helpful for the readers to refer to critical papers related to the PURE trial. Detailing the statistics for each section (based on specific studies) seem redundant as this is already published information and may not add to the novelty of the commentary.
- Figures 1 and 2 can be better formatted, the legends and the figure details are incredibly hard to read.
Author Response
I am thankful for being given the opportunity to review this commentary titled “Availability and affordability of medicines for diabetes and cardiovascular disease across countries: learnings from the Prospective Urban Rural Epidemiological Study” by Nguyen et al. The authors are highly respected physician-scientists in the field. This commentary offers to consolidate the findings on the availability and the affordability of medicines for diabetes and CVD, extracted from several informative studies as part of the PURE trial. There are, however, some comments that I would like the authors to consider.
- Much of the information presented in this article seems to have been written from the perspective of a review rather than a “commentary”. All subsections are more-or-less the summary statistics from previously analyzed data of the PURE trial. The current article lacks the critical insightful thoughts/learning that mandates from a commentary. For example, most of these insights/commentaries are limited to lines 100-107 for section 1, lines 130-132 for section 2, lines 167-171 for section 3, lines 198-201 for section 4, with some unique critique limited to lines 242-257.
Response: Thank you! We have provided further insightful comments in the manuscript.
- It seems like the take home message from the four subsections is that - the low-income countries are the ones suffering the most when it comes to either the availability or the affordability of medications related to diabetes and CVD. This may not be as surprising as one would assume that a country’s economic status (income level) intrinsically links to an individual’s/community’s health condition, however, the PURE trial emphatically provides the statistics for it. It would be insightful if the authors could include their own perspectives, and those from their physician colleagues who have been involved in these studies (the multi-enter, multi-nation PURE trial), and how their experiences in handling such patients (stratified based on economic/income conditions) rope into this current “commentary” article. A more nuanced discussion/commentary focusing on multi-factorial aspects on the outcomes of the PURE trial in context of the current article is required.
Response: We have provided further insightful comments in the manuscript.
- It has been a little more than 15 years since the PURE trial was initiated based on the World Bank’s stratification of a country’s economic status. Has this economic stratification changed in the current years, and are there any new studies that have altered the findings of the PURE trial as to what was observed from its data generated 15-17 years back?
Response: During the study time, several countries transitioned to other income categories, for example, India: LIC – LMIC (2009), China: LMIC – UMIC (2013), Colombia: LMIC – UMIC (2008), Iran: LMIC – UMIC (2010). Along with these transitions, their health systems may have changed as well. There are several more recent global surveillance studies, but they will all not be as comprehensive as PURE with respect to the contextual determinants, individual determinants and cardiovascular outcomes.
- A table summarizing the key statistics for each section (including the associated references) would be helpful for the readers to refer to critical papers related to the PURE trial. Detailing the statistics for each section (based on specific studies) seem redundant as this is already published information and may not add to the novelty of the commentary.
Response: Thank you for your suggestion but we would like to keep the current format.
- Figures 1 and 2 can be better formatted, the legends and the figure details are incredibly hard to read.
Response: We have revised the figures.
Round 2
Reviewer 2 Report
The authors have improved their manuscript by responding to our remarks. However, the conclusion currently presented (p15) integrating the limitations of this epidemiological study should be better structured with a clear and precise discussion, limitation and conclusion sections.
Author Response
Thank you for your time reviewing our manuscript. Please see our response to your suggestion as follows.
The authors have improved their manuscript by responding to our remarks. However, the conclusion currently presented (p15) integrating the limitations of this epidemiological study should be better structured with a clear and precise discussion, limitation and conclusion sections.
Response: We have restructured the current “Conclusion” part into “Discussion” and “Conclusion”, and adding the limitations within the “Discussion” part.
Reviewer 3 Report
The revised manuscript will be accepted for publication after the two minor changes are made-
1) Please include the following statement (response to one of the comments) within the conclusion section
During the study time, several countries transitioned to other income categories, for example, India: LIC – LMIC (2009), China: LMIC – UMIC (2013), Colombia: LMIC – UMIC (2008), Iran: LMIC – UMIC (2010). Along with these transitions, their health systems may have changed as well. There are several more recent global surveillance studies, but they will all not be as comprehensive as PURE with respect to the contextual determinants, individual determinants and cardiovascular outcomes.
2) The figure legends may have been revised but the figures are still of poor quality (none of the X or Y-axis labeling/the percentage numbers/color key can be clearly seen). Please revise.
Author Response
Thank you for your time reviewing our manuscript. Please see our responses to your suggestions as follows:
The revised manuscript will be accepted for publication after the two minor changes are made-
1) Please include the following statement (response to one of the comments) within the conclusion section
During the study time, several countries transitioned to other income categories, for example, India: LIC – LMIC (2009), China: LMIC – UMIC (2013), Colombia: LMIC – UMIC (2008), Iran: LMIC – UMIC (2010). Along with these transitions, their health systems may have changed as well. There are several more recent global surveillance studies, but they will all not be as comprehensive as PURE with respect to the contextual determinants, individual determinants and cardiovascular outcomes.
Response: We have added this in the new “Discussion” part.
2) The figure legends may have been revised but the figures are still of poor quality (none of the X or Y-axis labelling/the percentage numbers/color key can be clearly seen). Please revise.
Response: We have revised the figures.
