Subsiding ACTs in private sector in Niger: consequences and recommendations through a key

Transcription

1 1 2 3 Subsiding ACTs in private sector in Niger: consequences and recommendations through a key informant survey. 4 5 Jean-François Jusot 1, Oumarou Alto Centre de Recherche Médicale et Sanitaire (CERMES) 634, Boulevard de la Nation BP Niamey - NIGER Tél: (227) Fax: (227) Running title: Subsiding ACTs in private sector in Niger Name and address for correspondence: Dr Jean-François JUSOT jfjusot@gmail.com 20 1

2 Abstract Objectives Malaria is a major public health problem with substantial economic consequences in Niger. Artemisinin-based Combination Therapies (ACTs) are recommended to replace older drugs that are cheaper. An initiative "Affordable Medicines Facility Malaria" has been launched to make ACTs more accessible and affordable for patients. The aim of this study is to better understand the role of the private sector in the distribution of antimalarial drugs in Niger, and more especially ACTs to help implementing the AMFm initiative Methods A key informant survey was carried out to describe the drugs supply chain in Niger. They constituted retailers from wholesalers, pharmacies, general stores and drug depots. Selling prices, the main studied factor, were collected through a questionnaire Key findings Sixty nine interviews were conducted in Niamey and six other cities of Niger. ACTs with chloroquine, quinine and sulfadoxine-pyrimethamine were the most common antimalarial drugs supplied. The median price of a malaria treatment course reached 9.29 US dollars with ACTs as against 5.12 US dollars for artemisinin. The price of treatment course with chloroquine and sulfadoxine-pyrimethamine were 13 and 7 times less expensive than ACTs. Four wholesalers declared stock outs in antimalarial drugs during the previous month. The first reason given was a defect in the management of stockpiles. 2

3 Conclusions An improvement in the availability of ACTs could be done by implementing a performant and reliable information system, a reinforcement of existing regulations to limit the informal sector, and train public health actors, distributors as well as general public Keywords: malaria; antimalarials; supply and distribution; Niger 51 3

4 Introduction Malaria is a major public health problem with economic consequences in Africa and particularly in Niger, one of the poorest countries in the world. In 2000, malaria was the fourth leading cause of death in Niger, after acute lower respiratory infections, perinatal diseases and diarrhea among children less than five years (World Health Organisation. World Health Statistics Available from URL: [Accessed 2011 January 21]). In 2007, more than suspected episodes of malaria were reported to the national surveillance system. Eighty six thousand (86 000) were severe, with deaths, a case fatality rate of 0.15% (Annuaire des statistiques sanitaires du Niger. Année Available from URL: [Accessed 2010 December 21]). The use and affordability of Artemisinin-based Combination Therapies (ACTs) are part of five measures proposed by the Roll Back Malaria Programme to fight the disease (1,2). ACTs are recommended to replace older drugs (chloroquine, sulfadoxine-pyrimethamine) and have used as first-line therapy in Niger from However, the use of ACTs is hampered because of their limited accessibility due to the competition with artemisinin monotherapy and their price which is 10 to 20 times more expensive than older antimalarials drugs. As a result, the Global Fund to Fight AIDS, Tuberculosis and Malaria has launched an initiative called "Affordable Medicines Facility Malaria" (AMFm) in February The price of ACTs would be set between 0.2 and 0.5 US dollars (US$), similar to prices of older antimalarials. The decline in the price of ACTs in pharmacies could lead to a decrease in their margin. Nevertheless, AMFm s initiative is intended to prevent this by implementing supportive interventions (3). 4

5 The private sector is the more reliable in supplying quality medicines. It also represents a counterweight to informal market which is highly present in developing countries, particularly in Africa. The informal market supplies counterfeit and substandard antimalarial drugs of poor quality or even dangerous (4,5). In Niger, the distribution of malaria drugs is still poorly known. To our knowledge, only a local report shows that "the illegitimate market of drugs in Niger represents 70 to 80% of the national pharmaceutical market. The supply of the informal market is large with a variety of medications and other pharmaceutical products" (Diallo M. Contribution à l évaluation du marché illicite du médicament au Niger à partir des statistiques douanières d importation des médicaments, réactifs de laboratoires et consommables médicaux de 1999 à Report. Page 6.) The aim of this study was to inform the introduction of ACTs at low price to make them more affordable in the context of the AMFm initiative in Niger Methods Description of the AMFm initiative in Niger The AMFm aims to increase the availability of ACTs both to public and private sector. Selling ACTs at a sufficient low price make them affordable to socioeconomically defavourised people and allow a crescent use to the detriment of artemisinin monotherapies Price of eligible ACTs products are negotiated directly between Niger suppliers and some manufacturers who agree with the Global Fund on major ACTs supply. The Global Fund will pay a substantial portion of the price for eligible ACT products purchased by the eligible buyer equal to the co-payment amount for such products. 5

6 The buyer acknowledges that the operational priority of the AMFm is to reduce the price of quality-assured ACTs for patients in all sectors. The buyer commits oneself to sell co-paid ACTs with a reasonable margin, to replace the sale of oral artemisininbased monotherapies for artemisinin-based combination therapies in the treatment of malaria to delay the resistance to artemisinin The antimalarial drugs supply chain and the private sector in Niger Since 1995, a National Drug Plan Annual priority actions defined by the National Pharmaceutical Policy was launched to ensure an efficient and dense supply chain of drugs. Three main sectors are part of the supply chain of drugs in Niger: private non-profit (or public), private commercial and informal. The private non-profit or public market Its coverage reached less than 44.6% of the population of Niger. The only antimalarial drug currently distributed in health care facilities are ACTs in accordance with national policy on care of uncomplicated malaria. The ACTs are bought by Niger through the Office National des Produits Pharmaceutiques et Chimiques, and projects funded by the Global Fund, the World Bank and UNICEF. From time to time, the Niger receives donations of ACTs by Chinese cooperation. The Office National des Produits Pharmaceutiques et Chimiques supply health care facilities through 44 public pharmacies distributed in the 42 districts of Niger, nine pharmacies located in teaching and regional hospitals of the main towns, Niamey, Zinder, Maradi and Dosso and three drug depots located at Niamey, Zinder and Tahoua. The private commercial market It is comprised of 25 private drug importers or wholesalers, but only 9 are working. There are also 88 private pharmacies of which 71 (81%) are located in Niamey, and 6

7 general stores and drug depots registered at the Direction of Pharmacy. General stores and drug depots are located rather in rural areas devoid of pharmacies. The two biggest wholesalers purchase antimalarial drugs from international suppliers. Other wholesalers deal directly with suppliers. Private pharmacies are allowed to make their purchases outside the country to deal with occasional stock outs from local wholesalers. The informal sector It is composed of illegitimate, but tolerated stores or depots that have not renewed their authorization, and of street vendors encountered very often in markets and who provide parallel selling of drugs Conduct of the study A key informant survey was carried out at different levels of the supply chain from 20 April to 23 May 2009 (6). Key informants were the director of Department of Pharmacy, laboratory and traditional medicine of the Ministry of Public Health and regional public health authorities. They recommended to interview retailers from wholesalers, pharmacies, general stores and drug depots participating voluntary to the study. After key informants agree to participate, interviews were conducted by three trained investigators. Sellers from the informal sector were interviewed at unofficial sales points or at popular places such as markets. The questionnaire included the type and geographical location of supplier, the type and selling prices of antimalarials drugs, the sales volume, the sources of supply, the profit margins, the method and frequency of distribution of antimalarial drugs, the management of stockpiles and the frequency of stock outs, margin of retailers, advice given to the patients. The unit of price was expressed in Communauté Financière Africaine BCEAO Francs (XOF) and then converted into US$ with 1 XOF equal to 7

8 US$ ( Universal Currency Converter. Available from URL: [Accessed 2010 December 21]). The data entry was made by a single operator input using the software EPI Ethical approval All data were collected after consent of the key informants. The study was carried out after the authorisation of the Ministry of Public Health Statistical analysis A descriptive analysis was performed. Frequencies were used for qualitative variables and medians with interquartile range for quantitative variables. Since the sample was not randomly drawn, no confidence interval was given. The variability the price of an antimalarial treatment course was considered by the interquartile range. Because of various antimalarial drugs, the price of a malaria course was chosen to compare prices between distributors. It was calculated from the selling price of a box for ACTs (containing 16 tablets of arthemeter 20 mg and lumefantrine 120 mg) and artemisinin monotherapies (ART), a total of 15 tablets dosed at 100 mg for chloroquine, 7.5 g of quinine (five days of treatment at 25 mg / kg / day), 1.5 g of sulfadoxine-pyrimethamine. The doses were chosen from Vidal summaries or therapeutic recommendations of learned societies (World Health Organisation. L'utilisation des antipaludiques : rapport d'une consultation informelle de l'oms, novembre Global Partnership to Roll Back Malaria. 2001, Vidal Recos. Paludisme. Traitement. Available from URL: traitement [Accessed 2010 December 21], F Bruneel. POS traitment de l'accès palustre simple. Available from URL: [Accessed 2010 December 21]). 8

9 Statistical analysis was done using the software R version (R Development Core Team (2010). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN Available from URL: [Accessed 2010 December 21]) Results Study population Sixty nine interviews were conducted in Niamey and six other cities of Niger: in Niamey, 7 wholesalers, 12 private pharmacies, (representing 17% of pharmacies in Niamey); outside Niamey: 8 pharmacies (50% of the total), 11 pharmaceutical private and cooperative stores located outside Niamey (6% of the total), 20 illegitimate stores, and 11 street vendors Type of antimalarial drugs supplied Table 1 shows the type of antimalarial drugs sold by each type of retailer. ACTs with chloroquine, quinine and sulfadoxine-pyrimethamine were the most common antimalarial drugs supplied. Seven types of ACTs were found to be distributed: artemether-lumefantrine, artesunate-mefloquine, artesunate-sulfamethoxypyrazinepyrimethamine, artesunate-amodiaquine, dihydroartemisinine-piperaquine, dihydroartemisinine-piperaquine phosphate and sulfametoxy-pyrazinepyrimethamine-artesunate. Amodiaquine was more scarcely distributed which mefloquine or halofantrine. Seven vendors from the informal sector sold paracetamol as treatment course of malaria. Two unusual medicines were found on the market from Indian and Nigerian laboratories (respectively The De-Malaria and Kaka forte). 9

10 Price of a treatment course for malaria Table 2 shows the price of a treatment course for malaria according to distributors participating voluntary to the study. This price and the variability in the price of treatment were highest in pharmacies. For ACTs, the median price of a malaria treatment course reached 9.29 US$. The price varied depending on the retailer; 3.80 US$ in the informal sector vs in pharmacies. The profit margin was higher for stores and depots than for pharmacies (47.3% versus 35%). Prices of a treatment course showed a larger variation for depots and the informal sector than for other retailers For artemisinin alone, the price of treatment course was estimated at a median of 5.12 US$, with the highest prices observed in stores and depots (5.93 US$). The price of a treatment course varied largely more for ART than ACTs (IQR = 3.55 vs 1.31 US$ respectively) The price of treatment course with CQ and SP were 13 and 7 times less expensive than ACTs (0.69 and 1.33 vs 9.29 US$ respectively). Quinine administered by injection was 3 times less expensive than ACTs Stock out frequency The distributors of the private commercial sector were supplied with a large range, every day or at least every month by wholesalers. Vendors of the informal sector supplied with antimalarials from the local or regional market and more precisely one in four cases from neighbouring Nigeria and Ghana. Four wholesalers declared stock outs in antimalarial drugs during the previous month. The biggest constraints in the distribution of antimalarial drugs declared in Niger were transport conditions, competition with informal sector, purchase price of products, and 10

11 inadequacy or absence of implementing regulations. Another reason was a defect in the management of stockpiles because of the lack of an effective information system able to give in real time inventory of antimalarials drugs. Wholesalers also declared disruptions in supply (e.g. during dockworkers strike) Discussion This study was conducted to better understand the distribution of antimalarials in the private sector, formal and informal, in Niger. The choice of a key informant survey was done to highlight the variability in the supply of antimalarials, including ACTs. It was useful for AMFm initiative to get an order of magnitude of antimalarials selling prices, not to seek a representative sample of the structures involved in the distribution. This variability has been identified since seven classes of ACTs have been found alongside artemisinin, chloroquine, amodioaquine, quinine and sulfadoxine-pyrimethamine. This variability in practice is highlighted in several studies, through inappropriate advice to accompany the sale of antimalarial drugs, prescriptions not following recommendations or good dose or improperly using injection (7,8) The median price of a treatment course for ACTs has been estimated at 9.3 US$. According to the international drug price indicator guide, ACTs could be priced at 2 and 9.12 US$ respectively for artesunate - amodiaquine and arthemeter lumefantrine (Julie E. Frye. International drug price indicator guide Management Sciences for Health.). This is close to the median price found in this study, between 3.8 and 9.33 US$. For other antimalarials, this price is similar with that of a study conducted in Kenya in 2002, with the exception for ART (Table 3). This could be explained by the recent availability of ART on the market at the time the study was conducted in 11

12 Kenya (9). For quinine, prices vary between one to three times more, but that of Niger has a wide interquartile range. Unlike chloroquine, for which the price of a malaria treatment course is less than a dollar, ACTs remain virtually inaccessible considering the extremely low income of the majority of the population. Indeed, 60.6% of the Niger population lives on less than a dollar a day and 85.8% under 2 US$ a day (UNDP. Human development report 2007/2008.) Illegal market represents a large part of the pharmaceutical sector in Niger, especially outside Niamey; between 70% and 80% of the total number of providers according to a 2008 report based on customs data from 1999 to Although ACTs are commonly sold, other antimalarials, cheaper and less effective, are more requested by consumers of the informal sector. In addition, the quality of all medicines sold through the informal sector is questionable because of a lack of control of its sources of supply and inadequate storage. Indeed, in Cameroon, 12-74% of antimalarials sold illicitly, such as chloroquine, quinine and sulfadoxine-pyrimethamine, have been shown to contain no active substance (10). A study carried out in six towns of Nigeria showed that 37% of antimalarials sold in private and public healthcare providers did not meet the United States Pharmacopeia specifications for the amount of active ingredients, especially for quinine and sulfadoxine-pyrimethamine (5). Therefore, the subsidy mechanism which aims to improve access for ACTs by drastically lowering the selling price would compete with the informal sector in terms of volume of sales. However, the informal sector still accounts for a large market share in the sale of antimalarials, but distribution of quality medicines is not guaranteed by low prices. The results of this study show that pharmacies are a key element in the distribution of quality medicines compared to other distributors such as vendors of informal sector or 12

13 depots for which authorisations are not always up to date. One issue for the subsidy system will be to insure appropriate drugs according to clinical needs, at right doses in adequate periods and at lowest price (World Health Organisation (WHO) The rational use of drugs. Report of the Conference of Experts. Geneva: WHO. Resolution WHA54.11.). To face sale of counterfeit ACTs by informal sector, training street vendors or promoting network of stores or depots constitutes a real challenge in making more affordable ACTs The price of a malaria treatment course with injectable quinine was similar to ACTs. This is why quinine should remain the treatment of severe malaria as is currently recommended (World Health Organisation. L'utilisation des antipaludiques : rapport d'une consultation informelle de l'oms, novembre Global Partnership to Roll Back Malaria. 2001, Vidal Recos. Paludisme. Traitement. Available from URL: traitement [Accessed 2010 December 21]). It has been shown that price effectiveness of injection is strongly lower than oral use of chloroquin (11). In addition, injection of quinine may cause residual pain, abscesses, necrosis, and especially neurological deficit of lower limbs (12,13). Intramuscular injection to treat malaria could be the second cause of disability after poliomyelitis in children in 1982 in Niger (14). Since the 1980, poliomyelitis has known a sharp decline and intramuscular quinine with other injectable drugs could have become currently the first cause of deficit in the absence of awareness This study found that among ACTs, artesunate combined with mefloquine is distributed in Africa without sufficient toxicity data. Consequently, a study to 13

14 examine its effects is justified in the context of a wider distribution of ACTs when their price will reduce and be equivalent to that of chloroquine. Not to subsidize this type of ACT could be one of the recommendations Conclusions The study showed that the price of "ACTs" was too high compared with the standard of living of the Niger population and could justify the implementation of a mechanism for subsidizing ACTs, antimalarial drugs recommended by WHO. The "Affordable Medicines Faciliity - Malaria (AMFM)" relies on the drastic drop in the price of ACTs to eliminate monotherapies artemisinin-based antimalarials from market, by leaving the monotherapies at a high price. This reduction should also minimize the sale of other antimalarial drugs which have lower efficacy in reason of their growing resistance against Plasmodium falciparum This improvement in the availability of ACTs could be accompanied by resolving several potential problems depicted by the study: - A higher risk of stock out if a performant and reliable information system is not established, - A distribution with insuffisant quality of ACTs due to the predominance of the informal sector, tolerated despite existing regulations. Consequently, the quality of ACTs could be improved by training manger of depots and street vendors, - The predominance of informal market could be counterbalanced by extending depots network which could be managed by pharmacists, - The absence of a pharmacovigilance system that should detect side effects of some recent ACTs (combination of artesunate-mefloquine). 14

15 Acknowledgements This work was funded by the Clinton Health Access Initiative. Authors are indebted of Adam Swersky, from Clinton Health Access Initiative, who participated in the supervision of the study. CERMES acknowledges the General Director of Public Health Doctor Ali Djibo, the Director of the Department of Pharmacy, laboratory and traditional medicine of the Ministry of Public Health Doctor Matty and regional public health authorities of Niger for facilitating this study. CERMES acknowledges Bibata Abdou Sidikou who did the data entry. CERMES acknowledges all the participants, wholesalers, pharmacists, responsibles of stores and depots and street vendors of informal sector

16 References 1. Nabarro DN, Tayler EM: The "Roll Back Malaria" Campaign. Science 1998; 280: Le Bras M, Malvy D. [Malaria at the time of "Roll Back Malaria".] Med Trop 2004; 64: [in French]. 3. Resistance to the Affordable Medicines Facility for malaria? Lancet 2009; 373(9673): Newton PN, White NJ, Rozendal JA, et al. Murder by fake drugs. BMJ 2002; 324: Onwujekwe O, Kaur H, Dike N, et al. Quality of anti-malarial drugs provided by public and private healthcare providers in southeast Nigeria. Malar J 2009; 8: Marshall MN. The key informant technique. Fam Pract 1996; 13: Abuya T, Fegan G, Rowa Y, et al. Impact of ministry of health interventions on private medicine retailer knowledge and practices on anti-malarial treatment in Kenya. Am J Trop Med Hyg 2009; 80: Mannan AA, Malik EM, Ali KM. Antimalarial prescribing and dispensing practices in health centres of Khartoum state, East Mediterr Health J 2009; 15: Amin AA, Snow R. Brands, prices and registration status of antimalarial drugs in the Kenyan retail sector. Malar J 2005; 4:

17 Basco LK. Molecular epidemiology of malaria in Cameroon. XIX. Quality of antimalarial drugs used for self-medication. Am J Trop Med Hyg 2004; 70: Aina BA, Tayo F, Taylor O. Price implication of irrational prescribing of chloroquine in Lagos State general hospitals. J Infect Developing Countries 2008; 2: Assimadi JK, Gbadoe AD, Agbodjan-Djossou O, et al. [Diluted injectable quinine in the intramuscular and intrarectal route: comparative efficacity and tolerance in malaria treatment for children.] Med Trop 2002; 62: [in French]. 13. Ambroise-Thomes P, Carnevale P, Felix H, et al. Traitement du paludisme. EMC 1984; 8089: Thuriaux MC - A prevalence survey of lower limb motor disorders in school-age children in Niger and an estimation of poliomyelitis incidence. Trop Geogr Med 1982; 34:

18 Tables Table 1 - Antimalarial drugs declared to be sold by retailers from formal and informal sector. Antimalarial drug Wholesalers Pharmacies Stores and depots Illegitimate stores and street vendors (n = 7) (n = 20) (n = 11) (n = 31) ACT 7 (100) 19 (95.0) 9 (81.8) 7 (22.6) CQ 6 (85.7) 19 (95.0) 10 (90.9) 22 (71.0) Quinine 7 (100) 19 (95.0) 11 (100) 9 (29.0) SP 7 (100) 17 (85.0) 9 (81.8) 13 (41.9) ART 5 (71.4) 14 (70.0) 3 (27.3) 1 (3.2) AQ 1 (14.3) 1 (5.0) 0 6 (19.4) Others 1 (3.2) ACT = Artemisinin-based Combination Therapies, CQ = chloroquine, SP = sulfadoxine-pyrimethamine, ART = artemisinin, AQ = amodiaquine

19 383 Table 2 Cost of a treatment course of five antimalarial drugs in the formal and informal sector Antimalarial drug Wholesalers Pharmacies Stores & depots Informal sector All a n = 26 n = 220 n = 53 n = 108 n = 407 ACTs (n) Median (IQR) n (% of available data) 7.33 (2.39) 14 (93,3) 9.33 (1.12) 114 (85,1) 5.43 (6.61) 20 (100) 3.80 (3.90) 9 (81,8) 9.29 (1.31) 157 (87,2) ART (n) Median (IQR) n (% of available data) NA 5.13 (4.84) 10 (90,9) 5.93 (1.44) 2 (100) 4.61 (1.22) 4 (66,7) 5.12 (3.55) 16 (76,2) CQ (n) b Median (IQR) n (% of available data) NA 1.62 (1.97) 14 (66,7) 0.22 (0.10) 8 (88,9) 0.25 (0.10) 29 (82,9) 0.69 (0.59) 51 (77,3) Quinine (n) Median (IQR) for oral NA 10.7 (17.7) ID 1.63 (0.49) 3.08 (18.8) Median (IQR) for injection NA ID 9.90 (2.31) 10.2 (2.03) 8.14 (4.61) n for oral and injection (% of 10 (38,4) 3 (23,1) 7 (43,8) 20 (33,3) available data) SP (n) Median (IQR) NA 2.43 (1.15) 1.38 (1.11) 0.65 (0.45) 1.33 (1.67) 19

20 n (% of available data) 7 (33,3) 2 (22,2) 3 (12) 12 (21,1) a : Wholesalers not selling directly to patients, median of treatment course was calculated for pharmacies, stores, depots and informal sector b: The selling price is taking into account for a tablet of 100 mg, equal to 15 tablets for a treatment course of malaria ACT = Artemisinin-based Combination Therapies, ART = artemisinin monotherapy, SP = Sulfadoxine-pyrimethamine, ID = insufficient data, NA = not available, IQR = Interquartile range 20

21 Table 3 - Price of malaria treatment course according to studies led in Kenya and in Niger, and guide index of prices of medicines (in US$). Niger Kenya a GIPM b,c CQ 0.35 (0.30) 0.68 (0.29) 0.11 SP 0.67 (0.84) 0.59 (0.62) 0.14 Quinine (Oral) 1.56 (9.48) 4.53 (2.47) 1.03 ART 2.59 (1.79) 11.0 (2.80) NA 390 a The prices to Kenya have been updated taking into account the inflation rate between 2002 and i range). The prices are presented with median (interquartile b According to the guide index of prices of medicines. c The prices have been updated taking into account the inflation rate in Niger between 2003 and ii CQ = chloroquin, SP = Sulfadoxine-pyrimethamine, ART = artemisinin monotherapy, NA = not available 398 i ii