Availability, price, and affordability of antiseizure medicines in Addis Ababa, Ethiopia

Abstract Objective Up to 70% of people living with epilepsy could become seizure‐free with the appropriate use of antiseizure medicines. However, three quarters of people with epilepsy living in low‐income countries do not get the treatment they need and also do not access antiseizure medicines. The purpose of this study was to assess the availability, price, and affordability of antiseizure medicines in Addis Ababa, Ethiopia. Methods A cross‐sectional study was done in selected pharmacies using a questioner developed after the modification of World Health Organization/Health Action International methodology. Data on the availability and price of lowest‐priced generics and originator brand antiseizure medicines from essential medicines list in Ethiopia were collected from seven public sectors, five private sectors, and seven other sectors (five Kenema Public Community and two Red Cross Pharmacies) in Addis Ababa between 09 May and 31 2022. The data were analyzed using the modified World Health Organization/Health Action International workbook part I excel sheet. Descriptive results were reported in text and table format. Results The overall availability of lowest‐priced generics medication was 52%. The availability of lowest‐priced generics was 62.86%, 30%, 55%, and 50% in public, private, Red Cross, and Kenema Public Community Pharmacies, respectively. The median price ratio in the public, private, Red Cross, and Kenema Public Community Pharmacy was 1.45, 3.72, 1.46, and 1.7, respectively. All the medications were unaffordable. Patients may be required to pay more than 6‐month wage to purchase standard treatment for 1 month only. Significance The overall availability of antiseizure medicines was lower than the WHO target for noncommunicable diseases. All the available medicines were unaffordable.


| INTRODUCTION
Epilepsy is one of the most common neurological diseases globally. It is affecting around 50 million people worldwide. Epilepsy accounts for more than 0.5% of the global burden of disease. 1 Nearly, 80% of people with epilepsy live in low-and middle-income countries (LMIC). Prevalence of epilepsy is around three times higher in LMIC than in high-income countries. 1 The prevalence of epilepsy is higher in sub-Saharan Africa region than in other LMICs, also the prevalence was twice as in rural areas than in urban. 1,2 Most of the population in sub-Saharan Africa resides in rural areas, for example, 85% of the Ethiopian population lives in rural areas. The higher prevalence in rural area is likely due to the increased risk of endemic conditions such as malaria, neurocysticercosis; birth-related injuries; and variations in medical infrastructure, and the availability of preventive health programs and accessible care. 1,2 Not only the prevalence, the severity and consequences of epilepsy are greater in persons of low socioeconomic status. 3 The risk of premature death in people with epilepsy is up to three times higher than for the general population. 1 In many parts of the world, people with epilepsy and their families suffer from stigma and discrimination. The stigma and discrimination that surround epilepsy worldwide are often more difficult to overcome than the seizures themselves. 2 "Access to health care is a fundamental human right. However, the fundamental right to health cannot be realized without fair access to necessary medicines." 4 Access to affordable, quality-assured essential medicines is crucial to reduce the burden of disease. However, one-third of the world's population lacks regular access to essential medicines. The situation is significantly worse in Africa and Asia's poorest countries; where up to 50% of the population lacks such access. 5 Up to 70% of people living with epilepsy could become seizure-free with appropriate use of antiseizure medicines. 1 However, Three quarters of people with epilepsy living in low-income countries do not access antiseizure medicines. 1,2 The average availability of generic antiseizure medicines in the public sector of low-and middleincome countries is less than 50%. 1 The economic burden because of out-of-pocket costs and productivity losses creates substantial burdens on households. Unavailability and unaffordability are the main reason for nonadherence to treatment in low-income countries. 6 World Health Organization (WHO) has established a framework to assist policymakers in improving access to essential medications for universal health coverage by 2030. 7 One of the most significant barriers to access is high medicine pricing. 8 To ensure that medications are inexpensive, national policies, medicine pricing, and procurement strategies are crucial. To develop strategies and policies, there should be an adequate study about the current situation of the problems. The purpose of this study was to assess the availability, pricing, and affordability of antiseizure medicines in Addis Ababa, Ethiopia.

| Study area
In Addis Ababa, there are 13 public hospitals, among them six hospitals are owned by the Federal Minister of Health the other seven hospitals are owned by Addis Ababa City Administration.
Based on World Health Organization and Health Action International methodology (WHO/HAI) for measuring medication price, availability, and affordability, 8 the study was conducted at five public hospitals, two hospitals from the Federal-owned hospital (Amanuel Mental Specialized Hospital [AMSH], EkaKotebe General Hospital) and three from Addis Ababa City Administration hospitals (Zewditu Memorial Hospital, Yekatit 12 Hospital and Menelik Referral Hospital); five private pharmacies and seven other sector pharmacies (Red Cross and Kenema public pharmacies) found around those five hospitals. Two of the Federal public hospitals AMSH and EkaKotebe General Hospital primarily provide psychiatry and neurology treatment service. These hospitals provide service for patients referred from all over the country.
AMSH is the oldest and only mental specialized hospital in Ethiopia established in 1937. AMSH has around 268 beds for admitted patients.
EkaKotebe General Hospital was established in 2017 as the expansion of AMSH. It provides services with 350 beds. In addition to outpatient pharmacies, there is a special community pharmacy within the two mental hospitals, which is also included in the study. The other

Key points
• The availability of antiseizure medicines is short of the WHO target for noncommunicable disease.
• Public sector had better availability than the private and other sectors.
• Price of medication in the private sectors was higher than in public and other sectors.
• Antiseizure medicines are unaffordable in Ethiopia.
hospitals primarily provide outpatient services for neurology patients. In Addis Ababa, there are around 300 private retail pharmacies, 40 Kenema Public community, and 3 Red Cross Pharmacies.

| Study design and period
A cross-sectional study design was used to assess the availability, price, and affordability of antiseizure medications.
The study was conducted from May 09 to May 31, 2022 Addis Ababa, Ethiopia.

| Study population
All the medicines for this study were derived from the recent Ethiopian Essential Medicine List 2020 (EEML). EEML is developed based on the WHO essential medicine model list. 9 Medicines with different doses and dosage forms under the category of anticonvulsant from EEML include: Carbamazepine, Clonazepam, Diazepam, Lamotrigine, Lorazepam, Phenytoin, Phenobarbital, Sodium valproate, Gabapentin Ethosuximide, and Magnesium sulfate. 9 Among those medicines, Gabapentin and Ethosuximide were excluded from the assessment because these medicines are known to be currently unavailable in Ethiopia's public sectors, and also Magnesium sulfate is excluded because it is used commonly for the treatment of eclampsia in pregnant women rather than treatment of epilepsy in general population. Other than those three excluded medicines, all the other medicines with commonly used doses from EEML were included in the study.
The five hospitals were selected to represent both Federal and city administration and these hospitals provide epileptic treatment service for many patients from the city and referred patients from all corners of the country. Five private pharmacies around the hospitals were selected randomly after listing all the private pharmacies around the hospitals. Also, five Kenema Public Community Pharmacies and two Red Cross Pharmacies were selected for the study based on proximity from the hospitals.

| Sample size determination
Based on WHO-/HAI-standardized sampling methodology, 8 outpatient pharmacies in the five hospitals, two special community pharmacies found within the Federal public hospitals, five private retail pharmacies around the selected hospitals, five Kenema Public Community Pharmacies found within and around the hospitals, and two Red Cross Pharmacies near to the hospitals were included in the study, for a total of 19 pharmacy outlets. The two special community pharmacies within the two hospitals were included in the public sector.

| Data collection
A standardized data collection question was developed after necessary modification of the WHO/HAI methodology workbook part I for measuring medicine price, availability, and affordability. 8 The data were collected by four graduating fifth-year pharmacy students after providing adequate training on the data collection. The data regarding the availability and price of antiseizure medicines were collected from each selected pharmacy.

| Study variables
Availability, price, and affordability were study variables.

| Data processing and analysis
After data collection, data were entered and analyzed using WHO/HAI Medicine Pricing Workbook part II Excel sheet v 15.0, and the results were summarized and presented in tables.

| Data quality management
Pretesting was carried out at one private pharmacy to guarantee the clarity of the questionnaire and the data obtained. At the end of each data collection date, the supervisor checked the data collected for completeness. After data collection was completed, the random check was done by the supervisor on 20% of the outlets in order to ensure the quality of the data collected. The supervisor called four randomly chosen pharmacies to collect the same data in order to verify the accuracy of the data gathered previously. The pharmacists entered the data twice and cross-checked it to prevent errors. The workbook's data-checker feature was utilized to highlight data that should be validated.

| Availability
The availability of survey medicines was assessed by inspecting the lowest-priced generic (LPG) and originator Brand (OB) medicines in the pharmacy outlet. Medicine availability was calculated as percent availability of individuals and mean percent (%) availability across a group of medicines. It was calculated as outlets with the medication divided by the number of outlets included in the sector. Percent availability was calculated as:

| Price
In Ethiopia, most patients acquire medicine by purchasing out of pocket. Only few patients who are very poor have free healthcare coverage. Recently, the healthcare financing system have been started in some segments of the population.
The price of the medicine was obtained from the price list in the pharmacy outlet. Pharmacies in private mostly write the local price on the medicine package. The local price was changed to the US dollar using the exchange rate on the first day of the data collection. On the first day of data collection, 1US$ = 51.52 Ethiopian Birr (ETB). The median price ratio (MPR) of the medicine was calculated as the median price of the medicine in each sector divided by the International reference price of the medicine. 10 Median Price Ratio (MPR) was calculated as follows:

| Affordability
Affordability was calculated as the number of working days necessary for the lowest-paid unskilled government employee to purchase the specific medication for the 1month course of therapy. The daily wage of the lowestpaid government worker of Ethiopia was about 32.4 birr. 11 It was calculated as follows:

| Ethics approval and consent to participate
The study protocol was reviewed and approved by the Institutional Research Review Committee of Universal Medical and Business College with reference number IRRC/UMBC/454/14/2022. The owners of drug outlets were informed about the aims of the study prior to participation, and verbal consent was obtained from each drug outlet owner after explaining his/her right not to participate in the study. Confidentiality of the outlet was kept.

| Operational definition
• Affordability: It is calculated as the price of the medication for a month period divided by the lowest paid government worker wage. If the result is less than one it is affordable, if greater than one it is unaffordable. 8  The number of days' wage needed to purchase medicine used for a month was higher in the private sector (Table 3).

| DISCUSSION
The results of the current study showed that the overall availability of LPG antiseizure medicine was 52%. The  availability of antiseizure medicines is lower than WHO's target of 80% availability of the necessary medicines to treat noncommunicable diseases. 11 According to WHO essential medicines are the minimum medicines needed for the basic health system to function and the medicines should be available at all times. 12 Similar to other low-and low-middle-income countries, unavailability of antiseizure medicine could be a major reason for the treatment gap in Ethiopia. 1,13 Unavailability of antiseizure medicine is one of the reasons for nonadherence, increased morbidity and mortality, 6 and medication switch between generics and brand medication. Medication switches or changes in epilepsy patients may result in relapse of seizure episodes. 14,15 The study was conducted in the capital city where many of the health facilities in the country are situated and also many patients from regions are commonly referred to those studied hospitals for better management, however, most of the drug outlets do not have most of the essential medications needed. There are many reasons for the unavailability of the medicine. Civil war in Ethiopia, higher inflation rate, inadequate foreign currency for the importation of medications and poorly organized supply chain management system may be some of the reasons for unavailability of the essential antiseizure medicines. Additionally, less prioritization given to this disorder, insufficient health financing, inadequate skilled manpower, poor information generation and use on the disease and medicines need assessment, stigma from the disease, and poor patient treatment seeking may be some of the reasons for lower availability. Despite this, the availability of individual medicine was better than availability in many low-and middle-income countries like Zambia, 16 Madagascar, 17 Lao PDR, 18 and India. 19 The availability was similar to the Cambodia study 20 and lower than the Cuba finding. 21 The availability of LPG antiseizure medicines was 62.86%, 30%, 55%, and 50% at public, private, Red Cross, and Kenema public pharmacies, respectively. The results showed that antiseizure medicines were more available in the public sector. This was similar with Zambia 16 and Cambodia 20 but different from Madagascar. 17 In Madagascar, most antiseizures are available in the private sector. 17 The availability in public and private was lower than the Cambodia's finding (100% in public and 50% in private), 20 but higher than Zambia. 16 Unlike this finding, many studies indicated that there was better availability in the private sector than in the public sector. 5,11,22,23 In Ethiopia, most LPG medicines are supplied by the government procurement agency, the Ethiopian Pharmaceutical Supply Agency (EPSA). EPSA primarily supplies to public hospitals which is why it is better available in the public sector. Private sectors are not as such involved in the supply of antiseizure medications, this could be because of inadequate foreign currency and information on the amount of the medication needed. Private companies do not have adequate data on the real need for those medications. There is no clear source of information, especially for private suppliers, on the actual amount of the medicines needed in the country. If private companies feel the medication is not used by many patients they do not prefer to supply such type of medications. Unlike the private sector, other sectors are allowed to purchase medicines from EPSA, which may be the reason for better availability in other sectors than in private sectors. The findings of the current study also indicated that generic versions of the drugs are more available than originator brands. The availability of OB antiseizure medicine was very low. Similar to this study, most low-income countries and WHO regions of Africa and Europe do not have OB medicines in the public sector. 11,22 In most countries, the availability of OB medicine is better in private sectors than in the public sectors. 11,17,22 Among antiseizure only sodium valproate 200 mg tablet had availability (95%) higher than the WHO target in all sectors, 11 similar to Madagascar and Jordan's finding. 17,24 Also, Carbamazepine 200 mg tablet (82.8%), Phenobarbitone 100 mg, and Phenytoin tablet had higher than 80% availability in the public sector. This was higher than the average availability of all WHO regions of the world 22 and also higher than the average availability in each different income-level categorized countries, 22 Zambia, 16 Madagascar, 17 Jordan, 24 and Cambodia. 20 The availability of Diazepam 5 mg tablet was higher than in seven low-and lower-middle-income countries 25 and also other countries like Gambia, 23 Jordan, 24 and China. [26][27][28] Generally, the availability of sodium valproate, carbamazepine, phenytoin, phenobarbitone, and diazepam in this study was higher than availability in 46 countries with different income levels. 29 Addis Ababa is the capital city of Ethiopia, where many health facilities and specialized health services are provided. Also, many patients are sent to Addis Ababa for better management from all corners of the country. If at least essential antiseizure medicines are not adequately available, the patients may not have other options to access the medication anywhere in the country. In Ethiopia many patients have poor treatment-seeking behavior; poor medicine availability may result in decreased treatmentseeking behavior of patients.
In this study, the median price of antiseizure medication in private sectors was twice higher than in the public and other sectors. This is also the case at global levels, the price of medicine in private sectors is almost always higher than public sector. 17,22 When medications are not available in the public hospital, patients commonly purchase the medication from the nearby private pharmacy; Diazepam 5 mg/mL injection is commonly used but the availability was low (42.9%), and MPR was 11.2 and 81.07 in the public and private sectors, respectively. When diazepam injection was not available in the public sector, patients may be forced to pay more than seven times (81.07 divided by 11.2) in the private sector. Some of the reasons for the variation between public and private sectors could be that Ethiopia has a policy on the margin of price for medication, especially for public sectors, but this is not adequately implemented especially in private sectors 30 ; also running cost for private pharmacies is higher than public and other sectors; above all private sector are primarily established for profit generation but public and other sectors are established to serve the population with lower profit margin. Despite this MPR of carbamazepine and phenytoin tablets was lower than the MPR of those medications in 46 countries public and private sector. 29 Also, the MPR of LPG diazepam tablets in both public and private sectors was lower than the average MPR in global and all income-level categorized countries 22 and higher than the average Eastern Mediterranean and South East Asian WHO regions MPR. 22 The MPR was also higher than studies conducted in China, 28 Rwanda, 31 India, 19 and Indonesia. 32 This could be because there are different companies that produce generic products in those regions. Ethiopia imports 85% of the medications needed in the country. Most of the medications are imported from China and South East Asian countries like India. The cost of logistics is added to the Ethiopian price relative to those countries.
The price of phenobarbitone and sodium valproate for 1 month supply in private sectors was more than three times higher than the price in Zambia. 16 Also the price of sodium valproate 200 mg and carbamazepine 200 mg tablets was higher than the price in Madagascar. 17 This may be because difference in price negotiation between suppliers and purchasing organizations and also a difference in the cost of logistics and supply of the medicine.
The study also assessed the affordability of antiseizure medications in public, private, and other sectors in Addis Ababa, Ethiopia. Unlike most other studies, 19,20,24,28,31,[33][34][35][36] antiseizure medications assessed in this study were unaffordable. A patient with Epilepsy treated with sodium valproate 200 mg tablet required more than 2 months wage to purchase for 1 month medicine. Unaffordability was much higher in the private sector than in public and other sectors. Similar to Madagascar, 17 sodium valproate is the most available but very expensive medication. The unaffordability was increased even more when a combination of medication was used for a specific disease which is commonly seen in epilepsy treatment services. A patient with epilepsy required 18.3 and 11.1 days' wage in public and private sector, respectively, to purchase carbamazepine for 1 month (Table 3), but it required 2.7 and 5.2 days wage, respectively, in the public and private sectors in 46 countries from different income levels. 29 This indicates the lower daily wage in Ethiopia. Even though the price of the medications was lower or similar to the price in many countries, the purchasing power of the population in Ethiopia is very low. Relatively, the affordability of phenobarbitone and phenytoin was better than sodium valproate and carbamazepine (Table 3), According to WHO, essential medications should be available in a price that the community and individuals are able to afford. 12 In Ethiopia, the daily income of the lowest-paid government worker is less than one US dollar and most patients access health service through outof-pocket expenditure, so many patients are exposed to catastrophic health expenditure (CHE). The high unemployment rate in Ethiopia may also result in the increased rate of CHE. In Ethiopia there are many different barriers that hinder patients from using Epilepsy treatment services, these include socioeconomic issues, cultural factors, negative attitudes to the disease, fear, and unfamiliarity with the service. 1,2 Many patients using those medications have a higher disability and difficulty of involvement in income generation activities, this might increase the economic burden of the patient and the families caring for those patients. Unaffordability and out-of-pocket payment for health services may be reasons for abandoning health services from patients and caregiver side. Health insurance should be a decisive priority in Ethiopia. The public health insurance system is also a promising program for universal health coverage in Ethiopia. Publicly financed treatment of epilepsy could have the advantage of increasing patient productivity, and progressive health benefit and could help to resolve concerns related to equity in accessing health services. An economic study from India also estimated that public financing for both first-and second-line antiseizure therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective. 1 The unavailability of antiseizure medicines is a major factor in the treatment gap in low-and lower-middleincome countries. 13 In addition to unavailability, unaffordability of antiseizure medicines, and stigma from the disease can discourage people from seeking treatment. 1 As the prevalence, severity, and consequence of epilepsy are higher in low socioeconomic status, 1,3 unavailability and unaffordability could add to the burden of epilepsy in countries like Ethiopia.
Many studies indicated that switching antiseizure from brand to generic or from one generic to another may result in a relapse of the seizure, 14 interrupted supply, and unaffordability of antiseizure medication may require to switch the medication and could result in a relapse of the seizure episode.
By increasing the availability and affordability of antiseizure medicines, a number of people seeking treatment could be increased, and associated morbidity and mortality from the disease could be reduced significantly. Good availability and affordability are also associated with better adherence to antiseizure medications. 6 The limitation of this study was difficult to get full data from the Public procurement agency, EPSA about the procurement price of the medications, so it was excluded from the analysis. The other limitation was the study was done only in Addis Ababa, the capital city of Ethiopia, the result may be worse if it included the whole country.

| CONCLUSION
The availability of most antiseizure medicines was low in all sectors in comparison to WHO targets. Public pharmacies had better availability for LPG than Private sector. The patient price of the antiseizure medicines was not as different from international reference prices; however, most of the medications were unaffordable.

ACKNOWLEDGMENTS
We would like to acknowledge Universal Medical and Business College for supporting us by reviewing the protocol and approving a letter to undertake the study. Also, we would like to thank data collectors, owners, and heads of the health facility.
The authors received no funding for this study.

CONFLICT OF INTEREST STATEMENT
None of the authors have any conflict of interest to disclose.

ETHICS STATEMENT
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

DATA AVAILABLITY STATEMENT
All data are found in the manuscript, if additional is needed it can be accessed from the corresponding author on request.

SUPPORTING INFORMATION
Additional supporting information can be found online in the Supporting Information section at the end of this article.