Availability, price, and affordability of medicines used for the management of Covid-19 in health facilities of Dessie town WHO/HAI survey

Background The rapidly spreading nature of Covid-19 virus associated with its high mortality and mortality rate is triggering an unprecedented public health crisis. The study assessed the availability, price, and affordability of medicines used in the management of Covid-19 in health facilities of Dessie town. Methods A retrospective cross-sectional study design was employed in the health facilities of Dessie town from September 1 to September 20, 2021. Data was collected using a standard checklist adopted from the Logistics Indicator Assessment Tool and WHO/HAI. WHO/HAI methodology was applied to select the surveyed health facilities (30) and medicines (44). The daily wage of the lowest-paid unskilled government worker is used to estimate affordability. Results Fifteen and five medicines were not found at all public and private health facilities, respectively. The originator brand (OB) and lowest price generic (LPG) availability in private health facilities was 2.03% and 51.33%, respectively. In the public sector, the availability of OB and LPG was 0% and 34.44%, respectively. In public and private health facilities, the mean number of stock-outs was 2.25 and 2.91, and the mean number of stock-out days was 177.83 and 106.16 days, respectively. Eight and one LPG medicines were out of stock in public and private health facilities, respectively. Eight (33.33%) and 6 (28.57%) had higher prices than international prices in private and public health facilities, respectively. The median price ratio in public and private health facilities ranged from 0.02 and 3.05 and 0.04 to 2.70, respectively. Eighty percent of the products were unaffordable in both sectors. Conclusions The availability of medicines was low. One-third of the medicines had higher prices than international prices. Eighty percent of the products were unaffordable. The regular supply of these medicines is crucial for better management of the disease.


Results
Fifteen and five medicines were not found at all public and private health facilities, respectively. The originator brand (OB) and lowest price generic (LPG) availability in private health facilities was 2.03% and 51.33%, respectively. In the public sector, the availability of OB and LPG was 0% and 34.44%, respectively. In public and private health facilities, the mean number of stock-outs was 2.25 and 2.91, and the mean number of stock-out days was 177.83 and 106.16 days, respectively. Eight and one LPG medicines were out of stock in public and private health facilities, respectively. Eight (33.33%) and 6 (28.57%) had higher prices than international prices in private and public health facilities, respectively. The median price ratio in public and private health facilities ranged from 0.02 and 3.05 and 0.04 to 2.70, respectively. Eighty percent of the products were unaffordable in both sectors. Introduction price was doubled [20]. This made an increased demand for imported medicines and ultimately caused the prices of medicines to accelerate [21]. The availability, price, and affordability of medicines to patients are crucial. However, the COVID-19 pandemic affected the medical supply chain and created serious challenges to the quality of health care. Therefore, this study aimed to assess the availability, price, and affordability of medicines used to manage COVID-19.

Study area and period
The study was conducted from September 1 to September 20, 2021, in the health facilities of Dessie town, North-East Ethiopia. Dessie is one of the towns in the Amhara region preferred for medical tourism. In the town, there are 8 public health centers, one comprehensive hospital, one district hospital, 7 private hospitals, and 30 pharmacies. Public health facilities are managed by the local government and procurement of medicines was done independently by the Ethiopian Pharmaceutical supply agency (EPSA). Private pharmacies and private hospitals independently procure their drugs from wholesalers. The list of health institutions was obtained from the town health administration.

Study design
A retrospective cross-sectional study was conducted to determine the availability, price, and affordability of medicines used for the management of Covid-19 in the health facilities of Dessie town.

Study population and source population
The source populations for this study were all medicines available in health facilities. The study populations were medicines used for the management of Covid-19 in the health facilities.

Inclusion and exclusion criteria
All medicines used for the management of Covid-19 in the health facilities of Dessie town were included. Medicines that are not registered in Ethiopia and medicines that had incomplete records were excluded. We exclude drug stores as only a few medications were handled by them.

Sample size determination
Selection of healthcare facilities. According to WHO/HAI, a major center will be selected and an additional five survey areas will be selected randomly from all the administrative areas that can be accessed within one day of travel from the major center through a bus. For each selected survey area, five public health facilities and four public sector medicine outlets will be selected randomly within three hours' travel from the main hospital. In areas that have less number of health facilities, medicine outlets that are closest to each public medicine outlet will be selected [8]. Accordingly, 30 (20 private and 10 public) medicine outlets were selected for the study based on the WHO/HAI standardized sampling methodology.
Selection of medicines. The WHO/HAI methodology recommends sampling of all 14 global medicines and the addition of at least 20 supplementary medicines. All medicine included in this survey were taken from the list of "clinical management of Covid-19" developed by the WHO [22] and the "national comprehensive Covid-19 management handbook" developed by the Federal Ministry of Health of Ethiopia [3]. Fourteen registered global core lists of medicines to enable international comparison and 30 supplementary medicines based on their local importance (potential to manage COVID-19 and related infection) were included in the survey (S1 Table).

Study variables
The dependent variables of the study were availability, price, and affordability of medicines used for the management of Covid-19. The independent variables of this study were funding, selection, procurement, quantification, distribution and storage, income, and inventory management.

Data collection tools and procedures
Three pharmacists collected the data using a standard checklist adopted from the Logistics Indicator Assessment Tool (LIAT) [23] and WHO/HAI [8]. Physical identification (observation) and abstraction of the last six months' stock records (bin card, stock card, model 19, and model 22) of medicines in the stores and dispensaries were made to assess the availability and price of surveyed medicines. The principal investigators were the lead in the data collection process.

Data processing and analysis
Data were initially entered and then analyzed using Microsoft Excel 2010. Medicine availability was calculated as the percent availability of individual medicines. Availability was assessed in terms of point availability and period availability. Point availability was estimated by dividing the number of medicines available during data collection divided by the total number of medicines surveyed multiplied by a hundred. Period availability was calculated by dividing the number of medicines available in the review period (6 months) divided by the total number of medicines surveyed multiplied by a hundred. Availability of medicines was defined as < 30%, 30-49%, 50-80%, and > 80% for very low, low, fairly high, and high availability, respectively [24]. Stock out of medicine is the frequency and duration of usable stock unavailability (zero on the stock records) in the store or dispensary.
The results of price and availability were analyzed for each medicine. The median Price Ratio (MPR) indicates the ratios of medicine prices relative to a standard set of international reference prices. It was determined by dividing the median local unit price by the international reference unit price. The medicine prices were obtained from the Government Employees Medical Scheme (GEMS) [25]. The MPR of medicines was not calculated for medicines where the price was not indicated in GEMS. The finding of the MPR ratio indicates how much greater or less the local medicine price is as compared to the international reference price. The local currency value (Birr) during the day of data collection was converted to dollars. Gelders S et al. criteria were used to classify the value of MPR and an acceptable local price ratio was considered to be �1.5 [24].
Affordability has priced the ability of the lowest-paid unskilled government workers to pay for the cost of total treatment duration. The affordability of treating health problems was estimated by multiplying the daily defined dose, median price, and the number of days of the treatment course. The daily defined dose and number of days of the treatment course were based on the standardized treatment regimens set by the Federal Ministry of Health [3]. The median prices were taken from the result of the survey. Then, the cost of treatment episodes was compared to the daily wage of the lowest-paid unskilled government worker in the town. This was allowed to determine the number of days' wages the patient needed to pay for the full cost of treatment [26]. The daily wage of the lowest-paid unskilled government worker in the town was 0.44 Dollars (https://mywage.org/ethiopia/labour-law/wages). The formula used to calculate affordability is the total cost of medicine times thirty divided by the smallest salary of unskilled government workers [26]. The total costs of medicine for the completion of the duration of treatments for each disease were calculated. The total cost of treatment for acute health conditions was calculated by multiplying the median treatment price by the number of days required to treat the acute disease condition. The cost of medicines less than a day wage was taken as affordable, and medicines cost greater than or equal to a day wage were unaffordable. The difference in price and affordability was estimated through the Mann-Whitney test.

Ethics approval and consent to participate
This study was ethically approved by the Ethics Review Committee of the Pharmacy Department, Wollo University (CMHS 254/13). Written informed consent was obtained from all health facilities. To maintain confidentiality, coding was used and all medical records were fully anonymized.
Chloroquine phosphate 500 mg tablet, Chloroquine phosphate 250 mg tablet, Chloroquine phosphate 50 mg/5ml suspension, Chloroquine phosphate 50 mg/ml injection and Hydroxychloroquine 400 mg tablet were not managed in private health facilities. Originator brands were not available in the past six months in public health facilities. The availability of originator brands for Glibenclamide 5mg tablet, Paracetamol 500 mg tablet, Paracetamol 250 mg suppository, and Paracetamol 125 mg suppository were 25%, 25%, 16.6%, and 25% respectively. Cotrimoxazole 240mg/5ml suspension, Amoxicillin 500 mg capsule, and Diclofenac 50 mg tablet LPG were 100% available in all public health facilities. The lowest price generic of Amitriptyline 25 mg tablet, Amoxicillin 500 mg capsule, and Diclofenac 50 mg tablet were 100% available in private health facilities ( Table 1).
The availability of OB supplementary and global core list of medicines was 0%. The availability of LPG on the global core list of medicines in private and public health facilities was 72.5 and 57.85%, respectively. The overall OB and LPG availability in private health facilities was 2.03% and 49.33%, respectively. In the public sector, the availability of OB and LPG was 0% and 30.66%, respectively (Fig 1).
During the day of data collection, 8 and 1 LPG medicines were out of stock in public and private health facilities, respectively. Amoxicillin 500 mg capsule, Omeprazole 20 mg capsule, and Diclofenac 50 mg tablet LPG were 100% available in all public health facilities. The lowest price generic of Amitriptyline 25 mg tablet, Amoxicillin 500 mg capsule, and Diclofenac 50 mg tablet were 100% available in private health facilities. None of the OB was available in public health facilities. However, only OB of Glibenclamide 5mg tablet (25%), Paracetamol 500 mg tablet (25%), Paracetamol 250 mg suppository (16.6%), and Paracetamol 125 mg suppository (25%) were available in private health facilities ( Table 2).
The availability of supplementary LPG list of medicines was 40.16% and 22.25% in private and public health facilities of Dessie town, respectively. The availability of OB in private and public health facilities was 0% and 2.03%, respectively (Fig 2).  The frequency of public health facilities stock out medicines was ranged from 1 to 9 times. Stock out days ranged from 7 days to 295 days. On average, the number of stock out and the total number of medicines stock out days in public health facilities were 2.91 and 106.16 days, respectively. The number of stock outs in private health facilities ranged from 1 to 6 and the total number of day's stock out ranged from 14 to 360 days. The average number of stock out and the total number of day's stock out of medicines in public health facilities were 2.25 and 177.83 days, respectively ( Table 3).

Affordability of medicines
Affordability of medicines was measured in terms of the number of daily wages required to pay for treatment. Sixteen (80%) and 20 (80%) of the products were unaffordable in the public and private sectors, respectively. In the public sector, Amoxicillin-clavulanate 250 mg +125mg tablet (28.66), Amoxicillin-Clavulanate 1 gm tablet (17.24), and Cefepime 1gm vial for injection (14.63) were the most unaffordable medicines. In the public sector, drugs used for the treatment of Severe Pneumonia like Meropenem 1gm vial for injection, Ceftazidime 1gm vial for injection, Cefepime 1gm vial for injection, and Vancomycin 1gm and 0.5 mg vial for  (Table 5). There was no statistically significant affordability difference between public and private health facilities.

Discussions
The WHO developed guideline for case management of COVID-19 in health facilities aimed to suppress viral transmission, optimizing care for patients, saving lives, and minimizing the

List of medicines
Public Private

PLOS ONE
Availability, price, and affordability of COVID-19 medicines impact of the epidemic [22]. However, there are concerns about the steady supply of drugs [2]. In this study, the availability of supplementary LPG medicines was 40.16% and 22.25% in private and public health facilities, respectively. A systematic review conducted in Ethiopia reported that the average availability of essential medicine in public and private health facilities was 70.16% and 70.1%, respectively [27]. In Eastern Ethiopia, the overall availability of LPG was 46.97% (public 42.5% and private 50.8%) [28]. Another study also reported low availability [29]. Empiric literatures in China also reported low availability of medicines in private and public health facilities [30,31]. The availability of medicines decreased over time [32] and had a significant difference across the region of China [30]. The inadequate supply might be due to increased demand as a result of COVID-19. Pharmaceutical industries should help  governments to address the unmet needs by maintaining the steady flow of pharmaceuticals. Governments should also develop strategies to balance the drug supply chain in times of crisis [5].
The present study revealed that eight and one LPG medicines were out of stock in public and private health facilities, respectively. The frequency of stock out of medicine in public health facilities varied from 1 to 9 times and ranged from 7 days to 295 days. On average, the number of stock out and the total number of days stock out of medicines in public health facilities were 2.91 and 106.16 days, respectively. In private health facilities, the number of stock outs ranged from 1 to 6 and the total number of days' stock out ranged from 14 to 360 days. On average, medicines were stocked out 2.25 times and for 177.83 days. Ethiopian national average stock out days was 99.2 days [27]. It was also reported that less than half of the prescribed medicines were obtained from public pharmacies in Ethiopia and 17% of patients were forced to purchase medicines from private facilities [33]. The supply chain was unable to meet the growing demand for medicines used for the management of COVID-19 and made the medical supply chain to be fragile as most of the active pharmaceutical ingredients are being imported from China and India [4,34].
The MPR of medicines ranged from 0.04 to 2.70 in private and 0.02 and 3.05 in public health facilities, respectively. Eight (33.33%) and 6(28.57%) medicines had higher prices than international prices in private and public health facilities, respectively. In public and private sectors, Cotrimoxazole 240mg/5ml suspension (1.80), Paracetamol 500 mg tablet (1.84), Azithromycin 200mg/5ml suspension (2.70) and Amoxicillin-clavulanate 500mg +125mg tablet (1.88) had above the acceptable MPR value (1.5). However, the Mann-Whitney test showed that there was no statistically significant price difference among health facilities. Findings in Ethiopia revealed that the MPR of the private sector was more than four times higher than the international purchasing price in 30% of drugs [28]. Higher pharmaceutical price was found in the United States market [35,36]. The price difference between the public and private sectors was also apparent in China [31]. A statistically significant price difference was reported between the private and public sectors in Ethiopia [28] and China [31]. However, non-significant price variation was also reported in China [30]. It might be due to a wide price variation across countries for the same product. For example, some commonly used drugs in developing countries are more expensive than in developed countries [8]. The price of medicine is a key determinant in promoting access to medicine. The type of pharmaceutical policy used has reduced medicine procurement prices in Indonesia [37] and is recommended to be used in developing countries. Despite 16(80%) and 20(80%) products were being unaffordable in public and private sectors respectively, it was not statistically significant. The percentage of unaffordable medicines in Ethiopia was 72.09% and 91.84% in the public and private sectors, respectively [5]. Another study reported that 63.9% of the prescribed medicines were unaffordable [38]. The price of medicines in the private sector is higher than the public sector [39]. For instance, private sourced drugs are twice expensive in Ethiopia [33]. The price of medicine matters more to poor people and poor countries as the unavailability of essential medicines turn patients to the private sector and increasing the chance of incurring catastrophic health expenditure and making treatment very difficult [27]. To increase access to medicines, affordable prices should be the main objective of any pharmaceutical system and, hence any existing barriers that hinder access to medicines should be counteractedsix [5].
The present study will help health professionals and decision-makers to improve the steady supply of medicines used for the management of COVID-19. This study was not without limitations. MPR of some medicine was not calculated as the price was not indicated in the checklist. Being a cross-sectional study, we were unable to establish a cause-and-effect relationship. Moreover, the WHO/HAI methodology allows for to assessment of availability, affordability, and price at a single point in time which made difficult to exactly understand a single point.

Conclusions
Period and point mean availability of LPG medicines used for management of COVID-19 in private and public facilities was low and very low, respectively. In both sectors, OB availability was very low. Medicines encountered a high number of stock-outs. Fifteen and five medicines were not completely managed at all in public and private health facilities, respectively. Nearly one-third of the medicines had higher prices than international prices. Eighty percent of the products were unaffordable in both sectors. The regular supply of these medicines is crucial for better management of the disease.
Supporting information S1