Retail pharmacy prescription medicines’ availability, prices and affordability in Eswatini

Background Limited availability of medicines in public facilities and unaffordable prices in the private sector act as barriers to medicines’ access. Patients in Eswatini may be forced to buy medicine from the private sector resulting from chronic medicines’ shortages in public health facilities. The extent to which they can afford to do so is unknown. Aim To determine the availability, price and affordability of medicines in the retail pharmacies in Eswatini, and to compare the results regionally and internationally. Setting Retail pharmacy sector in the four administrative regions of Eswatini. Methods Data on availability, price and affordability to patients for 50 medicines in the originator brand (OB) and the lowest priced generic (LPG) equivalent, were collated using the standardised World Health Organization/Health Action International methodology from 32 retail pharmacies in the four regions of Eswatini. Prices were then compared with selected countries. Results The overall mean availability of all medicines in selected retail pharmacies was 38.5%; standard deviation [s.d.] = 20.4% for OBs and 80.9%; s.d. = 19.0% for LPGs. The overall median price ratio (MPR) in the surveyed pharmacies was 18.61 for the OBs and 4.67 for LPGs. Most standard treatments with LPGs cost less than a day’s wages whilst for OBs cost more than a day’s wages. The differences between Eswatini and South African prices were statistically significant. Conclusion Drug pricing policies and price monitoring tools are needed for the whole pharmaceutical chain in Eswatini to monitor availability, affordability and accessibility of medicines to the general populace.


Introduction
Although medicines are crucial in the healthcare system, they are generally not affordable to people globally. It is well documented in literature that prohibitive pricing is one of the major barriers to essential medicines' access. 1,2,3 There is significant underuse of costly medicines in populations that do not have any medical insurance, and thus, even the smallest price changes in drugs will impact adherence significantly amongst the poor. 4 More than 30% of the world population does not have reliable access to essential medicines. 5 In some of the poorest countries in Asia and Africa, the proportion is as high as 50%. Unavailability and/or low availability of essential medicines in the public health outlets may become a major barrier to medicines' access, especially when coupled with high unaffordable prices in the private sector. 6 It is thus imperative that prices in the private sector be affordable to ensure equitable access. 7,8 Medicines' expenditure constitutes between 20% and 60% of health expenditure in low-and middle-income nations compared to just 18% in the European nations. In developing countries, only a mere 10% have health insurance and the rest buy medication through out-of-pocket payments, which makes medication the biggest family expenditure item after food. 9 France and Italy utilise drug price controls to directly manage the drug prices. In Germany and Japan, prices are indirectly controlled via reimbursement under social insurance schemes. The National Pharmaceutical Price Authority in the United Kingdom (UK) monitors price by regulating the profits that companies make on branded prescription medicines' sales. 11 It is widely believed that the drug prices are generally higher in countries with less stringent price regulation (like the UK) or no regulation at all (the United States [US]) as compared to countries with strict price regulation. 12 The market share of originator brands (OBs) reduces significantly after the introduction of generics after the expiration of patent protection, and the competition between the generic options lowers the prices of the branded products further. 12 Free-pricing systems may lower the medicines' prices when optimum conditions are created, and as much as regulation in price-controlled systems may reduce the prices of both generics and brands, it may become a barrier to incentives to lowering prices below the listed ones. 10 Studies in the US in price variability with other commodities besides pharmaceuticals found that the poorer individuals usually find themselves paying more for similar goods and services as compared to their richer counterparts. 13 The grocery stores in poorer locations are usually smaller and more expensive than in the wealthier suburbs, mainly because of the existence of large chain stores in the more affluent areas and mainly independents in the poorer  areas. 13,14 Not much is known about price regulation or affordability in low-and middle-income countries, especially across the African region.
Eswatini is classified as a lower-middle-income country with the majority of the population living below the upper poverty line. 15 Although Mhlanga et al. 16 recommended implementation of a pharmaceutical pricing policy in 2016, there is still no price regulation of pharmaceuticals in Eswatini. 17 Mhlanga et al. 16 highlighted the importance of reliable evidence on medicines' prices in ascertaining the type of challenges in a system, before deciding on solutions to ensure availability of essential medicines at the lowest possible price to the consumer.
Prices for prescription medicines are a significant obstacle to appropriate medicine use. 18 It is not easy to find reliable medicines' prices' information in developing countries, 19 including Eswatini. The World Health Organization/Health Action International (WHO/HAI) has set a benchmark of 80% medicine availability as high to ensure the supply of essential medicines. 20 Although generic medicines are way cheaper than the OBs, they are still relatively unaffordable in many parts of developing countries. 21 The Medicines Regulatory Unit in the Ministry of Health is currently responsible for medicines' registration; however, a medicines' regulatory authority and pharmacy council are still to be established in Eswatini. 22 All prescription medicines (defined as any medicine on a valid doctor's prescription) attract value added tax (VAT) at 0%, and where there is no prescription, VAT is levied at 15%. 17 Cross-national differences in pharmaceutical prices are of great importance as they help governments to come up with appropriate domestic pricing policies. 23 South Africa, as Eswatini's neighbour, is considered as an upper-middle-income country and has introduced price controls for medicines. The single exit price (SEP) mechanism lists the price that a medicine can be sold by a manufacturer to an end dispenser. The South African Medicines and Related Substances Act (as amended) regulates the maximum additional dispensing fee that can be charged by people licensed to dispense and retail pharmacists, based on a tier structure directly tied to the SEP. All retail medicines attract a 15% VAT. 24 The Act has a provision that prohibits the use of bonuses, rebates or any incentives in the supply of medicines, to avoid undermining the SEP. 25 The aim of this study was to investigate the availability, affordability and prices that people pay for medicines in different parts of Eswatini. In addition, this study sought to ascertain how the medicines' prices in Eswatini were compared to the prices of the same medicines in South Africa and internationally.

Study design
A quantitative study using a cross-sectional descriptive design was employed.

Setting
Eswatini is a very small country, at just over 17 000 km² and a population of just over a million people and a population density of 66.1% people/m². It is located in southern Africa and is bordered by South Africa and Mozambique (see Figure 1). The country is divided into four regions: Hhohho (north-west: 28.5% of the population), Manzini (central: 30.5% of the population), Lubombo (east: 21% of the population) and Shiselweni (south: 20.5% of the population). 27 The urban population in Eswatini is 24.2%, and the unemployment rate was estimated at 23.4% in 2020. 27 Consultation fee is levied at $1.41 in the public sector, and medicines are free. 16 The lowest paid government worker in Eswatini earns a daily wage of $8.86 ($1.00 = Swazi lilangeni [SZL] 17.103 according to the exchange rate as at 15 June 2020). 28 Less than 20% afford medical insurance, and patients in Eswatini may be forced to buy medicines from the private sector because of the chronic medicines' shortages in Eswatini public health facilities. 16 Pricing surveys have been used to determine the extent of price differentiation and affordability in countries. Thus, for Eswatini, the WHO/HAI medicine price survey was used to identify medicine pricing and affordability in the country in order to provide policymakers and all stakeholders with evidence to draft policies that may improve availability, affordability and accessibility of medicines. 6,20 Study population and sampling strategy A list of pharmacies was obtained from the office of the Deputy Director of Pharmaceutical Services in the Ministry of Health of the 60 registered retail pharmacies in Eswatini at the time of the study, with 14 geographically situated in Hhohho, 30 in Manzini, 10 in Lubombo and six in the Shisweleni region. Stratified sampling was used to group the pharmacies. The primary criterion was the region of location for the pharmacy.
A total number of 32 pharmacies were included in the study. Random disproportionate stratified sampling was used to ensure that the sample was representative of the Eswatini retail pharmacy population. The sample comprised 12 pharmacies from Manzini, eight from Hhohho, six from Lubombo and six from Shiselweni. Simple random sampling was used to select the pharmacies to use in each region. To analyse the effect of the size of the city/town on prescription prices, pharmacies were categorised as from either city or town/rural area. Categorisation of pharmacy size was based on the population of the location: • City population ≥ 50 000 • Town/rural population < 50 000

Data collection
The survey included a total of 50 medicines (Appendix Table  1-A1). The list comprised the WHO/HAI Global Core List of 14 medicines and 36 supplementary lists based on the disease burden and local relevance in Eswatini. Expert advice was sought from pharmacists, medical doctors, academicians and Ministry of Health Professionals on the relevance of the selected medicines. For analysis, medicines were stratified by use (i.e. anti-infectives [AI] and non-communicable disease [NCD] medicines) and also on whether they were on the essential medicines list (EML) or not.
The managers and/or responsible pharmacists of the selected facilities were contacted via email and telephonically explaining the objectives of the study and the information that would be collected from their pharmacies. The responsible were informed that they were not obliged to participate in the study and that all identity information would be kept confidential.
Data collection took place between 15 June 2020 and 13 August 2020. Data on price, availability and affordability to patient were collected for two products, namely the OB and the LPG using the standardised WHO/HAI methodology. 29 The following specific data were collected for 50 essential medicines as per the WHO listing (14 from the Global Core List and 36 selected based on local relevance), 30 using the WHO/HAI workbook, 31 during visits to 'retail pharmacies': • The name of pharmacy, administrative region where located, and whether it was in a city or town/rural area. • Brand/product name and manufacturer of the LPG found at the site. • Availability of the OB and the LPG. • Pack size and price of the pack found for the OB and the LPG. • Any other comments regarding a given product.
During the retail pharmacy visits, data were recorded on hard copy medicine prices' data collection forms. The data collector made sure the data collection forms were complete and legible before leaving an outlet.
As per the standardised methodology, data collection forms were reviewed every day after completion of the fieldwork to ensure data quality. The data were then entered from the hard copy forms into the electronic survey workbook, and the double-entry programme was run, and any mistakes were corrected. Any questionable data identified after running data checker were investigated and corrected.

Data analysis
Data were entered in the pre-programmed WHO/HAI Microsoft Excel Workbook. 31 The workbook automatically generated analysis of the data entered once complete, giving summary tables of percentage availability and median price ratios (MPRs). 31 Median local prices were expressed as ratios to international reference prices (IRPs), using the formula: Medicine price = median local unit price ratio (MPR) International reference unit price [Eqn 1] Management Sciences for Health (MSH)'s 2015 prices were used as the default IRPs. 32 The IRPs used are prices offered to international not-for-profit agencies for purchase of generics.
The availability of medicines was determined as a percentage of outlets where medicine was found on the day of data collection. Mean availability of the 50 medicines was also reported. The differences in average percentage availability of OBs and LPGs determined if there was any variance in the availability of the two product types. To describe availability, the following ranges were used as reference: 19 • < 30% extremely low • 30% -49% low • 50% -80% fairly high • > 80% high.
The MPR pharmacy prices for each drug were compared across region categories using analysis of variance (ANOVA). The MPR pharmacy prices for each drug were compared between the two categories of location size using t-test. The lowest and maximum prices in Eswatini were compared to the lowest and highest permissible retail prices in South Africa (based on current dispensing fee guide in South Africa at the time), 33,34 and the differences were expressed as percentage price difference for similar products and were analysed using the t-test for statistical significance.
Affordability was calculated as the number of wage days that the lowest paid government worker needed to spend to pay for treatment and was based on the median local price of a medicine prescribed at a standard dose. All analysis was carried out using Statistical Package for Social Sciences (SPSS) version 27 (University of KwaZulu-Natal, School of Health Sciences).

Distribution of pharmacies
A total number of 32 pharmacies were included in the study. Twelve pharmacies were drawn from Manzini region, eight pharmacies from Hhohho region, six pharmacies from Lubombo region and six pharmacies from Shiselweni region. Of the 32 surveyed pharmacies, 13 of them were located in cities and 19 in towns and rural areas.

Medicines' availability on the day of data collection
The overall mean availability of all medicines in the surveyed retail pharmacies was 38 between the two locations was statistically significant (p = 0.001).
The availability of LPGs was high in the city and fairly high in the town located pharmacies, with pharmacies in the cities registering 87.4% availability and the outlets in towns and rural areas recording 76.5% availability. Results showed that this difference was statistically significant (p = 0.001).
The overall availability of all the different groups analysed was generally high for the LPGs and low for the OBs. The global core medicines had the highest LPG mean availability (89.2%; s.d. = 9.0%), followed by AI at 86.7%, then EML medicines with 85.1%, followed by 82.3% for the NCD medicines and then 77.7% overall mean availability for the supplementary medicines ( Table 1). The differences between the different regions in terms of availability of LPGs of the different classes were not statistically significant. A similar trend was observed with respect to availability of the different medicines' groups in both cities and smaller towns and the rural areas.

Consolidated private retail sector patient price ratios
Of the 50 medicines surveyed in the 32 outlets, price ratios were calculated for 33 OBs and 48 LPGs (where medicines were found in four or more outlets

Regional patient price comparison
Overall patient prices in Shiselweni were approximately 4% and 8% more than patient prices in Manzini region, whilst the Lubombo prices were approximately 42% and 9% more in comparison with Manzini for OBs and LPGs, respectively. The overall MPR patient prices in Shiselweni were approximately 7% cheaper than the prices in Hhohho for the LPGs. Analysis of variance results showed there was no significant difference between the regions in terms of LPG prices (p < 0.719).
A few of the LPGs had large price differentials across the different regions. The LPG omeprazole 20 mg cap/tab was sold to patients at 3.18 MPR in Manzini, but was available at more than four times that price in Lubombo and Shiselweni regions. Comparatively in the Hhohho region, the patients had to part with almost 10 times the Manzini price. The LPG furosemide was available at 2.12 MPR in Manzini, required more than 3 times this in Lubombo and Shiselweni, and was available at 9.38 MPR in the Hhohho region. Atenolol 50 mg, diclofenac 50 mg and fluoxetine 20 mg also showed large price differentials across the regions. Overall patient prices in the cities were 3% more and 5% less than patient prices in the smaller towns for OBs and LPGs, respectively. The LPG diazepam 5 mg was available to patients at 1.12 MPR to patients in the cities, whilst it was sold at 6.58 MPR in the smaller towns.
OB price ratios were only analysed for Hhohho and Manzini regions as the other two regions did not have significant OB availability for any meaningful comparison. Overall, patient prices in Manzini were approximately 3% and 1% more than patient prices in the Hhohho region for OBs and LPGs, respectively. Results showed that the difference between Manzini and Hhohho OB medicines' prices was not statistically significant (p = 0.166).

Comparison of retail prescription drug prices in Eswatini and South Africa
Of the 32 OBs that were found in more than four outlets in Eswatini only two products, diclofenac 50 mg capsule/tablet (cap/tab) and amlodipine 5 mg cap/tab had their highest prices equal to the maximum permissible South African patient price, whilst eight products had their Eswatini highest prices lower than the maximum permissible South African patient prices, and the rest had Eswatini highest prices that were more than the maximum permissible South African patient prices (see Table 3). The differences were statistically significant (p = 0.004). Only one product, carvedilol 12.5 mg cap/tab, had its lowest Eswatini unit price lower than the cheapest South African patient price, whilst the lowest prices for all the other OBs were higher than the lowest prices in South Africa of the same products. The differences were statistically significant (p = 0.14).
Of the 48 LPGs analysed, one product, tamsulosin, had its Eswatini lowest price equal to South Africa's lowest generic patient price, 26 products' Eswatini lowest prices were higher than South Africa's lowest prices and 18 products had their lowest prices lower than corresponding South African LPGs for the same molecules. The lowest prices of simvastatin 20 mg and omeprazole 20 mg were more than 300% lower than the lowest generic patient prices in South Africa. The lowest and highest LPG prices for South Africa were calculated using the MRPs from the Mediscor platform. 34 Of all the LPGs that were analysed, only 11 products had Eswatini highest prices lower than the South African maximum permissible patient prices in the retail pharmacies. The other 37 products had highest prices, higher than the highest generic patient prices for similar molecules in South Africa. The difference in the prices was statistically significant (p = 0.014).

Treatment affordability
The LPGs for the most common AI were generally affordable in all the regions, with an adult 7 days' course of amoxicillin, a paediatric 7 days' course of co-trimoxazole and a paediatric 7 days' course of amoxicillin + clavulanic acid, all requiring less than a day's wages of the lowest paid government unskilled worker to purchase them (see Table 4). The first line of management for diabetes mellitus 2 (DM II) was affordable for both the OBs and LPGs in all the four regions of Eswatini, with a monthly course of 60 tablets of glibenclamide 5 mg requiring less than 0.5 days' wages to purchase. It is worth noting that less than 0.8 days' wages were required to purchase a course of either the OBs or the LPGs of metformin 500 mg in the four regions. Gliclazide was less affordable and required more than the equivalent of the lowest paid unskilled government worker's single day wage to purchase a course for 1 month of the LPGs. No LPG was found for human insulin (30% regular/70% isophane) in all the surveyed areas and the OB required 5.20 days' wages in Manzini, 5.36 days' wages in Hhohho and 7.37 days' wages in the Lubombo region. Table 5 illustrates the affordability of a 3-drug regimen when OBs and LPGs when purchased from the retail pharmacy sector in Eswatini. The lowest paid government worker would have to work 2 days to afford the LPG regimen, and in case the LPGs are not available, she/he will have to work for 4.8 days to be able to afford the OBs.

Discussion
The study showed that the overall availability of the LPG medicines in all the regions was higher than the recommended minimum availability benchmark of 80% 20 set by WHO/ HAI. It can be deduced from the results that there is promotion of generics' dispensing as compared to the branded products in all the regions. The more affluent settlements are in Hhohho and Manzini regions, and the availability of OBs was comparably higher in these two regions. Guan et al.'s 35 findings highlighted the challenges associated with regional disparity of essential medicines.
Another study looked at the undiscounted prices for both OB and the LPG for 25 essential medicines from 17 private pharmacies in Shaanxi Province, western China. It noted that   Table 2 Continues on the next column→ generics were more available as compared to OBs and prices varied across different discount programmes. The study concluded that price transparency of pharmaceuticals helps consumers in the identification of potential savings. 36 The overall availability of LPGs was not different in all the regions. However, the pharmacies located in cities had higher availability than the ones in smaller towns and rural areas for both LPGs and OBs. A survey conducted in Peru using the WHO/HAI medicines' prices and availability survey did not find any significant differences in overall availability or prices of the medicines under study by retail location. 15 It is commendable that the availability of LPGs on the EML was more than 90% in all regions, and as such in the event of medicines being unavailable at government hospitals, patients can access medications at retail pharmacies.
It was quite interesting to note that the LPGs' prices were comparable in all the four regions and the differences reflected were not statistically significant. Although there is currently no price regulation administered by the government, 37  A careful analysis of the molecules that had large differentials, for example, omeprazole 20 mg, showed that the overseas parallel generic imports were available at a significantly lower price to the patients as compared to similar generic molecules that were sourced regionally. The clients in the more affluent locations are generally brand-sensitive as compared to patients in the rural settings, where outlets can afford to keep the most affordable non-branded import generics. There is a need for the authorities to ascertain that these lowly priced molecules also meet the stipulated quality standards.
The study showed that generally the OB patient prices were higher in Eswatini when compared to prices of the same prescription molecules in South Africa, and this is not a deviation from the expected as literature suggests medicines' prices in regulated environments are generally lower than in countries with no price regulation. 23 Eswatini procures their OBs from South Africa where pricing is regulated, and as such, the best/lowest cost to the retail outlets for these would be at the SEP price and as such it is expected that the retailing prices will be higher than SEP in the Eswatini outlets. Eswatini prescription medicines' prices have VAT at 0%, 4 whereas in South Africa all medicines attract VAT at 15%. If the VAT regulation in Eswatini would change from 0% to the standard 15%, 24 the Eswatini prescription medicines will become more expensive to the end users.
The Eswatini market is not limited to the South African generic molecules only as they also have access to parallel import generics from overseas which were found to be generally cheaper than the South African equivalent molecules. The difference in the gross domestic product (GDP) per capita per month between South Africa and Eswatini needs to be considered, 8 as a small price difference may turn out to be huge with respect to affordability in the Eswatini context.
Most first-line treatment regimens for NCDs were generally affordable, requiring less than a day's wages. It is worth noting that more than 60% of Eswatini's population lives below the upper poverty line of $8.21 per capita per month, and as such, 8 treatment regimens calculated as affordable may still be way out of the range for the general populace. 16 There is usually more than one family member requiring chronic medications, and even though the individual courses may be affordable, the combined regimens will be unaffordable. Anti-epileptic medications and most second-line management regimes required more than a day's wages; hence, unavailability at the public hospitals could lead to patients defaulting their treatments.

Limitations
Affordability was calculated based on the daily wage of the lowest paid unskilled government worker, but a large portion of the labour force is not employed by the government and the minimum wages are way lower than the salary of the lowest paid government worker, thus the data may not be a true reflection of affordability in Eswatini.
Availability refers to the day of data collection at each facility and might not be indicative of average availability over time. Availability and prices' data were collected during level 2 lockdown (as a result of the [coronavirus disease 2019] COVID-19 pandemic) when supply chains were disrupted, and hence, these findings may not be a true reflection of the availability throughout the year (Eswatini depends entirely on imports as there is no manufacturing of any pharmaceuticals that takes place in the kingdom).

Recommendations
Future research should focus on comprehensive national surveys in all public and private entities to determine medicines' prices, including from the wholesalers. Price components throughout the entire pharmaceutical supply chain should be studied. Focus on these will assist in developing policies that will work towards improving affordability and availability.

Conclusion
Drug pricing control by the government is one of the factors responsible for lower retail prices in South Africa. The concept of 'free market economy' in Eswatini may not be enough to regulate the prices of medicines. There is a need to develop drug pricing policies that govern the whole supply chain. 16 However, for that to happen all the necessary data on the current pricing structure in the whole pharmaceutical supply chain of Eswatini should be gathered. The Medicines and Related Substances Act of 2016 allows for the implementation of a pricing system for medicines in Eswatini. 17