Koduah et al. Systematic Reviews (2022) 11:257 https://doi.org/10.1186/s13643-022-02114-z RESEARCH Open Access Implementation of medicines pricing policies in sub-Saharan Africa: systematic review Augustina Koduah1* , Leonard Baatiema2, Anna Cronin de Chavez3, Anthony Danso‑Appiah4, Irene A. Kretchy1, Irene Akua Agyepong5, Natalie King6, Timothy Ensor7 and Tolib Mirzoev3 Abstract Background: High medicine prices contribute to increasing cost of healthcare worldwide. Many patients with limited resources in sub‑Saharan Africa (SSA) are confronted with out‑of‑pocket charges, constraining their access to medicines. Different medicine pricing policies are implemented to improve affordability and availability; however, evidence on the experiences of implementations of these policies in SSA settings appears limited. Therefore, to bridge this knowledge gap, we reviewed published evidence and answered the question: what are the key determinants of implementation of medicines pricing policies in SSA countries? Methods: We identified policies and examined implementation processes, key actors involved, contextual influences on and impact of these policies. We searched five databases and grey literature; screening was done in two stages fol‑ lowing clear inclusion criteria. A structured template guided the data extraction, and data analysis followed thematic narrative synthesis. The review followed best practices and reported using PRISMA guidelines. Results: Of the 5595 studies identified, 31 met the inclusion criteria. The results showed thirteen pricing policies were implemented across SSA between 2003 and 2020. These were in four domains: targeted public subsides, regulatory frameworks and direct price control, generic medicine policies and purchasing policies. Main actors involved were government, wholesalers, manufacturers, retailers, professional bodies, community members and private and public health facilities. Key contextual barriers to implementation were limited awareness about policies, lack of regulatory capacity and lack of price transparency in external reference pricing process. Key facilitators were favourable policy environment on essential medicines, strong political will and international support. Evidence on effectiveness of these policies on reducing prices of, and improving access to, medicines was mixed. Reductions in prices were reported occasionally, and implementation of medicine pricing policy sometimes led to improved availability and affordability to essential medicines. Conclusions: Implementation of medicine pricing policies in SSA shows some mixed evidence of improved avail‑ ability and affordability to essential medicines. It is important to understand country‑specific experiences, diversity of policy actors and contextual barriers and facilitators to policy implementation. Our study suggests three policy implications, for SSA and potentially other low‑resource settings: avoiding a ‘one‑size‑fits‑all’ approach, engaging both private and public sector policy actors in policy implementation and continuously monitoring implementation and effects of policies. *Correspondence: akoduah@ug.edu.gh 1 Department of Pharmacy Practice and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana Full list of author information is available at the end of the article © The Author(s) 2022. 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The Creative Commons Public Domain Dedication waiver (http://c reat iveco mmons. org/ public doma in/z ero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Koduah et al. Systematic Reviews (2022) 11:257 Page 2 of 27 Systematic review registration: PROSPERO CRD42020178166 Keywords: Policy implementation, Medicine pricing policies, Sub‑Saharan Africa Background framework [20, 21]. There is, however, limited pub- Over the past decade, the cost of accessing safe and qual- lished evidence summarizing influences on the imple- ity healthcare has increased rapidly globally, attributed mentation of medicines pricing policies across low- and largely to the high prices of medicines [1]. Additionally, middle-income countries (LMICs). there are concerns that most of the highly priced medi- Most medicine pricing policies have been imple- cines do not necessarily translate into improved health mented in high-income countries, but there is paucity outcomes [2]. In response to high and increasing medi- of empirical data/evidence on implementation poli- cine prices, medicine pricing policies have been imple- cies in LMICs, especially sub-Saharan Africa (SSA). mented to regulate prices of medicine and improve Understanding medicine pricing policy implementa- financial access [3, 4] to safe, quality and affordable medi- tion is particularly important as implementation of cines, one of the sustainable development goals in attain- these policies can be a major challenge in LMICs where ing universal health coverage by 2030 [5–7]. A medicine many patients with extremely limited resources need to pricing policy can be defined as a set of written principles provide out-of-pocket payments, thus impeding their or requirements for managing the prices of medicines access to medicines and putting them at further risk agreed or adopted by a public institution, a group of pur- with increasing prices [11, 22]. Other studies focused chasing organizations or individual health services [8]. only on the following: effects of reference pricing in Various medicine pricing policies exist to regulate sup- organization for economic cooperation and develop- ply of essential medicines [8]. These policies can be cat- ment (OECD) countries [13], government initiatives egorized into (a) regulatory framework and direct price to mandate drug pricing transparency [23], ensuring control, e.g. reference pricing, mark-up regulation, vol- access to psychotropic medication [24], factors contrib- untary license agreement and tiered pricing; (b) targeted uting to the increase in pharmaceutical expenditures public subsidies, e.g. affordable medicines schemes; (c) [25] and generic drug policies in Brazil, Russia, India, generic medicine policy, e.g. promoting generic pre- China and South African (BRICS) countries [26]. scribing and use; and (d) purchasing policies, e.g. pooled With this backdrop, we conducted a systematic procurement. Reference pricing is the practice of bench- review on available medicine pricing policies in SSA, marking or referencing a medicine price to the price in their implementation processes, contextual influ- one or several countries or purchasing authorities [8]. ences and impacts on prices and access to essential Reference pricing remains a key policy widely employed medicines. We addressed the main question: what are globally as a regulatory policy [9–13]. Mark-up regula- the key determinants of implementation of medicines tion represents the additional charges and cost applied to pricing policies in sub-Saharan African countries? The the price of a medicine along the supply chain, and this review addressed four interrelated questions: includes setting a single exit price at the ex-factory level [8]. Generic medicine policies are widely recommended (1) Which medicines pricing policies have been imple- and applied in many contexts [14–16] to influence medi- mented in SSA and what are their key elements? cine prices through competitions [8]. Pooled procure- (2) How have these policies been implemented (in ment through a single entity on behalf of individual relation to implementation approaches, processes, purchasing authorities promotes competitive prices from involvement of actors and their underpinning evi- manufacturers and suppliers [16–18]. dence)? The implementation of medicine pricing policies is (3) Which key facilitators and barriers affected imple- influenced by multiple contextual barriers or facilita- mentation of medicines pricing policies and how? tors of implementation approaches and processes. The (4) What were the effects of medicines pricing poli- facilitators include increased competition, skilful nego- cies with regard to reducing prices and improving tiations, pragmatic supply management and bulk pur- access to medicines? chasing [19]. Medicine pricing policies are challenged by the prevailing market conditions in a particular This review is aimed particularly at health policy context, including proximity to particular medicines, analysts, healthcare professionals, implementation sci- quantities purchased and functionality of regulatory ence scholars and decision-makers who are engaged in improving access to medicines in LMIC settings. K oduah et al. Systematic Reviews (2022) 11:257 Page 3 of 27 Methodology Screening The review was conducted as part of a study on A screening decision flowchart was agreed within the ‘Improving equitable access to essential medicines in review team, which followed inclusion and exclusion cri- Ghana through bridging the gaps in implementing teria (see Additional file 2). medicines pricing policy, which involved collabora- We included all empirical studies (randomized con- tion between University of Ghana, Ghana Health Ser- trolled trials (RCTs), quasi-experimental studies, cross- vices and University of Leeds, with funding from the sectional and cohort studies) and reviews in English or National Institute for Health Research (NIHR), UK’. French possessing the following criteria: The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) • A focus on medicine pricing policies to improve the Statement [27]. The review protocol was registered in affordability of medicines in the country the International Prospective Register of Systematic • A focus on how the policy processes were imple- Reviews (PROSPERO, reference: CRD42020178166) mented and published [28]. • A SSA context, published since 2000 with relevant information available for analysis Search strategy We excluded studies that were as follows: The literature search was initially run in April 2020 to identify studies covering implementation of medi- • Opinion pieces, commentary or conceptual/theoreti- cine pricing policies in SSA. We updated and re-ran the cal publications searches on 25th May 2021 in Ovid MEDLINE(R) ALL • Policy analyses which focused solely on the agenda- 1946 to May 24, 2021, Embase (Ovid) 1996 to 2021 week setting and development stages 20; Global Health (Ovid) 1973 to 2021 week 20, Web • Conducted two plus years prior to 2000 but pub- of Science Core Collection, Scopus (Elsevier B.V) and lished after 2000 as this predates the MDG and Sus- African Index Medicus (via World Health Organization tainable Development Goals (SDG) agenda (WHO) Global Health Index Medicus). We also searched • In languages where we were unable to resource trans- for grey literature in the Institutional Repository for lation or where full text was unavailable Information Sharing (WHO) [29] and the World Bank Open Knowledge Repository [30]. For additional French- French articles were screened, translated and data speaking articles, we searched the Erudit (University of extracted by native French speakers on the research Montreal) [31] and Cairn International (Cairn.info) data- team. Screening was conducted in two stages using the bases [32]. review management software Rayyan [34]. The first stage Search strategies were developed using the major con- screening focused on the titles and abstracts and the sec- cepts: sub-Saharan African countries, medicine pricing, ond on full texts. To ensure consistency across the team, medicine policy and implementation. Database subject the initial titles and abstracts of 50 records were indepen- headings and free text words to search titles and abstracts dently screened by eight researchers, and the results were were identified by the information specialist and project discussed to reach consensus and standardize approach team members. The search terms and strategy were peer and calibration. The remaining records were then ran- reviewed by a senior information specialist using the domly allocated (295 each) for independent screening. PRESS Checklist [33]. The searches were not limited by One researcher (T.M) screened the remaining records language but were restricted to studies published since and co-screened 20% of the records from each reviewers’ 2000. This date was chosen following the introduction subset for consistency. In the second stage, full-text arti- of the Millennium Development Goals (MDG) in 2000, cles were independently reviewed by two researchers (A. which included a global focus on improving access to C, L. B) against the inclusion criteria. Discrepancies were medicines and services. However, we did not search thee resolved in discussion between these members and with Department for International Development (DFID) or involvement of two further reviewers (A. K. & T. M.). contact experts for additional papers as envisaged in the original protocol. Full search strategies are available in Quality assessment Additional file (see Additional file 1). Quality assessment on the included studies was per- The results of the database searches were stored and formed independently by two researchers (A. C., L. B.) de-duplicated in an EndNote X9 library. Further relevant using the relevant critical appraisal checklists from the studies were added by citation searching of the included Joanna Briggs Institute to assess the methodological qual- studies from the following reviews [13, 23–26]. ity of the eligible studies. Where discrepancies existed, Koduah et al. Systematic Reviews (2022) 11:257 Page 4 of 27 two other reviewers were consulted (A. K., T. M.). Three approach (processes, actors, evidence use); and any facili- quality assessment tools for cross-sectional analytical tators and barriers to policy implementation and their studies, cohort studies and qualitative studies from the effects. Extracted data were coded in identifying the main Joanna Briggs Institute tools were used. For the analytical themes emerging as shown in Table 1. cross-sectional quality assessment, eight domains were assessed as ‘Yes (present), No (absent), Unclear (insuffi- Data analysis and synthesis cient information) or Not Applicable’ [35]. The checklist Due to the heterogeneous nature of medicines pric- for the qualitative studies has 10 domains assessed as ‘Yes ing policies, and the countries involved, we conducted a (present), No (absent), Unclear (insufficient information) thematic narrative synthesis of the data [38], which fol- or Not Applicable’ [36]. Similarly, the checklist for the lowed the four review questions. The thematic summa- cohort studies has 11 items and is assessed as yes (pre- ries in Table  1 were developed drawing on the review sent), no (absent), unclear (insufficient information) or not questions to categorize the study findings into thematic applicable [37]. The checklist criteria were not modified groups [38]. The findings were synthesized, organized but interpreted flexibly to reflect our focus on the imple- and reported around the main themes and subthemes. mentation of medicines pricing policies. As a result, the overall scores or results were presented narratively to Results reflect the presence (yes) or otherwise (no) of which of The final searches identified 5505 records, and citation the domains. searches identified a further 90 records. Once dupli- cates were removed, there were 2528 records. Screening Data extraction and coding by titles and abstracts identified 134 records for full-text Two authors (A. C., L. B.) extracted the data from all the review, and 31 studies were eligible for inclusion, data 31 studies using a Microsoft Word template. The forms extraction and analysis. Studies were excluded based were designed to include publication details (author, on wrong outcome (n = 57) because the intervention of date, country, study design; date study conducted); medi- interest was not present, population (n = 5), study type cines pricing policy (key elements, effects on prices, (n = 28) such as commentary and theoretical publica- effects on healthcare access); the policy implementation tion, publication type (n = 4) and background article (4) Table 1 Themes and subthemes Themes Subthemes Medicines pricing policies implemented Targeted public subsides Regulatory framework Generic medicines policies Purchasing policies Policy implementation approach Use of private distributors Regulatory framework Use of evidence in the policy implementation design Type of evidence used Actors involved in policy implementation Government Retailers Wholesalers Manufacturers Professional bodies Donor agencies Public and private health facilities Barriers to policy implementation Contextual factors serving as barriers at micro level (i.e. individual/personal) Contextual factors serving as barriers at meso level (i.e. organizational) Contextual factors serving as barriers at macro level (i.e. national systems) Facilitators to policy implementation Contextual factors serving as facilitators at micro level (i.e. individual/personal) Contextual factors serving as facilitators at meso level (i.e. organizational) Contextual factors serving as facilitators at macro level (i.e. national systems) Effectiveness of implemented policies Control or reduce medicine price Improve access to healthcare, i.e. availability and affordability K oduah et al. Systematic Reviews (2022) 11:257 Page 5 of 27 or duplicate (2), not SSA (n = 3), and these are detailed sufficient information about the study participants and in the PRISMA flow diagram (Fig. 1). The eligible stud- settings. However, only six studies provided information ies were drawn from multiple study designs but mostly to indicate how potential confounding factors were iden- quantitative nature, cross-sectional in nature (e.g. [39– tified or accounted for, and similarly, little information 44] and retrospective studies (e.g. [45–47]). The char- existed on how confounding factors were addressed. For acteristics of studies included in the review are listed in the qualitative studies, only one study reported informa- Table 2. tion on the philosophical perspective, making it difficult to establish congruity with the research objectives and Quality assessment methodological approaches adopted. However, congruity Results of the quality assessment are presented in Addi- was established between the research methodology and tional file (see Additional file 3). For cross-sectional ana- the data collection methods, analysis and interpretation lytical studies, a total of 22 out of the 23 studies reported of the results. None of the studies also reported how the a clearly defined inclusion criteria for the recruitment researcher could have potentially influenced the research of participants and description of outcomes to be con- process. Lastly, for the cohort studies, the nature of the sidered for the study. All the eligible studies provided studies did not permit quality appraisal of the three Fig. 1 PRISMA flow diagram to illustrate the screening process from the initial search until the final selected studies (Page et al., 2021) Koduah et al. Systematic Reviews (2022) 11:257 Page 6 of 27 Table 2 Characteristics of the studies included in the review sample size, study design and settings Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Ali and Yahia, Sudan To compare Cross‑sectional Survey of 174 Pharmacy and Regulation of Wholesal‑ N/A N/A ‑Shortage of ‑23% of N/A 2012 [36] national pricing survey medicines Poisons Act pharmaceuti‑ ers, National trained personnel C&F prices with retail prices, (2001) cal prices using Medicines and and resources approved adherence of the current Poisons Board, to assess cost by NMPB prices, com‑ fixed mark‑ups manufacturers and freight (C&F) were over parison of generic of 15% and and retailers prices 10 times the medicine pricing, 20% of the ‑Lack of scrutiny international demonstrate total cost for on medicine pric‑ reference violations and put wholesalers ing information price forward recom‑ and retailers, by regulators ‑The whole‑ mendations respectively ‑No pricing sale and retail control, e.g. prices were medicine prices of 40% and 47% certain generics less than that higher than their approved by originators NMPB respec‑ tively ‑E leven out of 12 originator medicines were ≥ their retail prices published in the British National Formulary ‑Prices distrib‑ uted by Cen‑ tral Medical Supplies was 2‑fold their C&F price K oduah et al. Systematic Reviews (2022) 11:257 Page 7 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Ali, 2009 [48] Sudan To evaluate the Mixed meth‑ Ninety‑three Revolving drug N/A Ministry of N/A Initial funding N/A ‑Cost of RDF RDF facilities revolving drug ods: structured patients at the fund Health support from prescription had increased fund (RDF) effect interviews and exit points of Save the Chil‑ donors was perceived access to essential on accessibil‑ documentary selected public dren (UK) as affordable medicines, with ity of essential analysis health facilities. by users with 97% availability medicines and its Ninety‑three improved during the past 12 impact on the uti‑ health facility quality months lization of public users in hospi‑ compared to health services tals and health previously free centres, 5 with medicines the RDF and 2 ‑Medicines without. One for chronic teaching hos‑ diseases were pital outpatient considered department, 1 expensive rural hospital ‑Patients in and 3 health non‑RDF centres (urban, facilities spent peri urban and more than rural) those in RDF facilities, with 67% able to afford their medicines and 8% discontinued due to cost Koduah et al. Systematic Reviews (2022) 11:257 Page 8 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Ashigbie et al., Ghana To examine Qualitative Public and Reimburse‑ Reimburse‑ ‑Public and N/A An essential ‑Lack of stand‑ ‑Lower prices Patients may not 2016 [49] medicines study using private sector ment of medi‑ ment for cost private health medicines ardization of mark at CMS does have access to managements semi‑ providers cines to health to private and facilities list facilitates ups (25–50%) not apply medicine because policies under structured (government facilities public health ‑Pharmacies reclaim costs of and high market in pricing in not all facilities Ghana’s NHIS, interviews and mission facilities ‑Licenced a wide range prices of medi‑ retail phar‑ participate in the from perspectives hospitals, pri‑ chemical of medicines cines macy scheme and not of public and vate hospitals shops ‑Reimbursement ‑The current all medicines are private sector and private ‑Christian delays pricing captured in the providers standalone Health Associ‑ system, in NHIS reimburs‑ pharmacies), ation of Ghana both public able list pharmaceutical Facilities and private suppliers and sectors, is NHIS district of limited office benefit in controlling escalating medicine prices Bangalee and South Africa To examine Quantitative Five classes of Generics and Manufacturers N/A N/A Prices lowered N/A ‑The SEP N/A Suleman, 2016 cardiovascular study — cardiovascular single exit could sell their based on mar‑ policy has not [45] originator and secondary data disease drugs price (SEP) medicines at ket availability resulted in generic drug analysis legislation uniform prices competitive prices using inter‑ prices national reference ‑75% of prices generic drugs were 40% or more cheaper than the branded ones Bangalee and South Africa To compare Quantitative Prices taken Generic medi‑ SEP mandates N/A N/A N/A ‑Lack of prices N/A N/A Suleman, 2019 prices among study based from 18 medi‑ cines and SEP manufactur‑ regulation [46] originator, on private cines in study ers to sell at a ‑Established pseudo‑generics sector prices of uniform price relationship for and generics medicines originator com‑ panies creating challenges for generic manufac‑ turers K oduah et al. Systematic Reviews (2022) 11:257 Page 9 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Cassar and South Africa To assess whether Quantitative Not docu‑ External refer‑ SEP aimed to ‑Pricing com‑ N/A N/A ‑The use of ERP Ex‑manufac‑ N/A Suleman, 2019 international economic — mented ence pricing regulate, pric‑ mittee does not adopt a turer price [50] benchmarking of observational (ERP) [39] ing, remove ‑National multidimensional reduced by medicines (IBM) analysis policy rebates and Department of approach 68%, 85% with comparator discounts Health ‑Emergence of and 85% of countries would negotiated confi‑ products in lower medicine dential discounts 2016, 2017 prices locally and 2018, respectively Cohen et al. Tanzania To assess the Household Sixty‑four N/A N/A N/A N/A Awareness People not being N/A ACT use from 2013 [51] first 1.5 years of longitudinal ADDO shop campaigns aware that arte‑ round 1 to 3 Affordable Medi‑ survey and owners. misinin combina‑ increased cines Facility for interview, Sixty‑four tion therapies malaria (AMFm) surveys and sub villages, (ACTs) were a use in Tanzania customer exit Seven‑hundred better treatment interviews households option in round 1 and 756 in rounds 2 and 3. Total = 3900 individuals d’Almeida, et al. Cameroon The study Mixed methods Not stated Free medicines Free second‑ National Coun‑ N/A Free second‑ ‑Lack of inte‑ N/A Problems led to 2011 [47] presents lessons — interview; line treatments cil for the Fight line treatment grated informa‑ very limited num‑ learnt from provi‑ semi‑open for HIV/AIDs Against HIV/ facilitated tion systems on ber of patients sions of second‑ questionnaires AIDS, National by external HIV/AIDS patients getting 2nd‑line line treatments Direction to funding ‑Deficiencies in treatments for HIV and AIDS Fight Diseases, the supply chain/ Provincial logistics for 2nd‑ Centers for line treatments Treatment de Jager and South Africa To determine the Quantitative, Beneficiaries Generics and N/A Govern‑ N/A N/A A small number Average price Utilization of rosu‑ Suleman, 2019 impact of gener‑ retrospective from registered reference ment, pricing of generics reductions vastatin increased [44] ics and generic medical pricing committee, manufacturers in range from from 24.0 to reference pricing schemes who pharmacists, South Africa 13.9 to 31.0% 63.9% and then on candesartan were con‑ Pharmaceuti‑ for rosuv‑ 76.4% following and rosuvastatin tracted with cal Society of astatin and the introduction the PBM for the South Africa candesartan, of the generic entire study and Retailers respectively reference pricing period Koduah et al. Systematic Reviews (2022) 11:257 Page 10 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Fink, et al. 2014 Uganda To determine the Cross‑sectional Targeted retail Affordable N/A ‑Global fund N/A N/A ‑Public sector AMFm ‑ACT increased [41] effect of AMFm survey‑baseline outlets includ‑ Medicines ‑UNITAID stock outs, high benchmark from 51 to 68% on the use of survey ing small, Facility for ‑Gates Foun‑ prices in drug was achieved ‑More shops ACTs informal, unli‑ malaria dation shops and phar‑ even prior to stocked ACTs, censed shops macies the arrival of leading to 52% and vendors ‑Limited geo‑ the program AMFm to licensed graphic coverage and sustained pharmacies throughout Guimier et al. Senegal To highlight dif‑ Wholesale Reimburse‑ Reimburse‑ Private N/A N/A N/A ‑The com‑ Only 5% of 2005 [52] ferences between distributors ment policy ment of and public ponents of patients had not the price of drugs and 532 private medicines pharmacies, the public taken their pre‑ in Senegal and pharmacies in the public wholesalers, price vary scribed drugs for the population’s operating sector manufacturers, only slightly financial reasons ability to pay for through a laboratories, between the them network of distributors four catego‑ pharmaceutical ries of medi‑ depots and the cines: taxes National Sup‑ (1.3–1.4%), ply Pharmacy freight, insur‑ ance and local transit (5–6%), distribution margins (40–48%) and PGHT (46–54%) Honda and Madagascar To assess the Household Households. Pooled Community Govern‑ N/A Knowledge of Financial and Out‑of‑pocket Equity fund Hanson, 2013 outcomes of the survey Three case procurement participatory ment and implementa‑ geographical payments members have [53] equity funds in studies & user fees: approach Community tion status constraints lower for increased access Madagascar from Case 1 — equity fund representatives accessing health members to the public three perspec‑ urban (all centre than non‑ health facility tives amenities) members Case 2 urban/ rural (subur‑ ban) Case 3 rural (few basic amenities) K oduah et al. Systematic Reviews (2022) 11:257 Page 11 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Liu and Galár‑ Angola, This study aims to Price survey No participants ‑Essential N/A N/A N/A ‑Transaction N/A ‑Generic sta‑ N/A raga 2017 [54] Botswana, (i) analyse global Descrip‑ medicines list volume tus 8/10 ARVs DRC, Leso‑ ARV prices from tive drug ‑National or ‑HIV preva‑ had lower tho, Malawi, 2004 to 2013 price trends social health lence prices than Zambia and (ii) examine 2004–2013 insurance originat Mozam‑ the relationship ‑Procurement ‑All six first‑ bique, of national drug strategy line ARV drug Namibia, policies to ARV unit prices South Africa, prices decreased Swaziland over time, Tanzania and from a 46% Zimbabwe price decrease for lamivudine to 90% price decrease for efavirenz Maiga, et al., Mali To analyse the Qualitative Not docu‑ Government Set up a Managers, N/A High involve‑ Disagreement Estimated N/A 2010 [55] role of govern‑ study mented price regula‑ commission, pharmaceuti‑ ment of private between the 25% theoreti‑ ment interven‑ tion policy price ceilings, cal companies, and public public and private cal reduction tion and market monitoring employers’ sector stake‑ sector on the basket forces in price and evaluation council, union holders of 107 medi‑ regulation, pri‑ system and workers and cine vate sector pric‑ define working pharmacy ing of essential methodology professionals medicines and for access to pricing process medicines in Mali’s private pharmaceutical sector Maïga, and Mali To assess the Price survey, a Sixteen Generic essen‑ N/A ‑Government N/A Education N/A The median The availability Williams‑Jones impact of the cross‑sectional wholesalers tial medicines ‑Private and and creating wholesale was judged to be 2010 [40] national pharma‑ descriptive and 30 private public health‑ awareness price of the the same before ceutical policy on survey drugstores care sectors 49 drugs and after the supply system for was 14.3% policy generic essential and 25.6% medicines cheaper than the maximum price in 2006 and 2009, respectively Koduah et al. Systematic Reviews (2022) 11:257 Page 12 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Maı̈ga, et al., Mali To study cost Price survey Pharmacies Cost recovery N/A N/A N/A N/A N/A Costs of Access to drugs 2003 [56] recovery and and observa‑ and public and generics prescriptions was improved generics policies tions of health centres were lower affordable gener‑ customers where public ics were widely health facili‑ available, even in ties had been private outlets revitalised Moodley, R. South Africa To evaluate the Longitudinal No participants Single exit N/A N/A N/A N/A N/A Upon intro‑ N/A and Suleman, impact of SEP on before and — data used price policy duction of the F., 2019 [57] a basket of origi‑ after evaluation ‘The Global intervention, nator medicines, study Core of four‑ the medicines in terms of costs, teen items (14) showed an and impact on originator and immediate prices forty‑six (46) drop in price generics with a subse‑ quent rate of increase being much less than before Moodley, R. South Africa To examine the Quantitative Prices of 50 Single exit N/A ‑Manufacturers N/A N/A N/A The SEP had N/A and Suleman, impact of the reg‑ study originator price policy ‑Pricing com‑ a larger effect F., 2019 [58] ulatory change, medicines on generics mittee on generics the SEP, on a were assessed prices ‑Ministry of pricing than basket of generic from 1999 to health originator. medicines from 2014 Most medi‑ 1999 to 2014 cines showed a smaller yearly increase in price compared to before regula‑ tions Nicolosi, E. and South Africa To assess the Economic All the medi‑ Generic medi‑ N/A N/A N/A N/A N/A 67.5% were N/A Gray, A., 2009 potential savings evaluation cines listed cines policy more than [59] by substituting study in 25 chronic 40% cheaper generics for disease algo‑ than branded brand rithm made medicines. All by the Council generics were for Medical priced lower Scheme Koduah et al. Systematic Reviews (2022) 11:257 Page 13 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Ongarora, et al. Kenya To assess Survey using Forty‑five pri‑ Generic medi‑ N/A N/A N/A N/A The lack of regu‑ Clients paid N/A 2019 [60] retail pricing, standardized vate healthcare cines Policy lation of prices higher prices availability and electronic facilities in 14 than the affordability of questionnaire of Nairobi’s median IRPs medicines in low‑income for 68.6% private facilities settlements of generic (18 clinics, 7 medicines hospitals, 2 selected health centres, 4 medical cen‑ tres, 2 nursing and maternity homes, 12 pharmacies) 28 innovator products were included Ponsar, et al., Mali To assess the Survey Pregnant Subsidized/ N/A ‑MSF (doc‑ N/A Free provision Payment of user Savings in Utilisation of 2011 [39] impact of abolish‑ women and free medicines tors without medicines fees drugs reduced healthcare ing user fees children under for malaria borders) the overall increased fourfold on utilization of five treatment ‑Health centres consultations for under 5 s; by essential health ‑Ministry of cost the end of the services and Health period, 3.5 × mortality more pregnant women were being treated for fever Koduah et al. Systematic Reviews (2022) 11:257 Page 14 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Rothberg, et al. South Africa To measure Prospective All medicines Reference pric‑ N/A ‑Medscheme’s N/A Willingness of Low enrol‑ Price move‑ N/A 2004 [61] the impact of and retrospec‑ for which ing for generic medicines some manu‑ ment into the ment for reference‑pricing tive analyses generics medicines management facturers to programme eligible programme of prices of products were ‑Interpharm drop prices products for covering items for medicines available teams the 12‑month available generic Quantitative — ‑Government period equivalents price survey showed that 19.6% of prod‑ ucts dropped prices, 16.8% increased by up to 10%, 19.5% by 11 — 15%, 7.8% by 16 — 50%, 1.7% up to 100% and 1.0% by more than 100% Sabot, et al. Tanzania To evaluate the Cross‑sectional Drug shop Affordable N/A Wholesalers N/A ‑Popularity of ‑Cost is still a Consumers Increase in the 2009 [38] extent to which study — exit customers, Medicines and retailers designated barrier for poorer purchas‑ proportion of patients use rec‑ interviews, retail audits Facility‑malaria retail outlets customers ing ACTs shops stocking ommended ACTs retail audits, ‑Global policy ‑Stock‑outs and for children ACTs in the inter‑ and its implica‑ mystery and funding challenges with under 5 paid vention districts, tions for AMFm shoppers, and the supply chain significantly from 0/133 in implementation public facility less than August 2007 to audits those buying 109/151 (72.2%) for adults in August 2008 Smith, et al. Kenya To measure Survey All public Affordable N/A Government N/A ‑Proximity to ‑Most of the drug Brands pur‑ Increased access 2011 [37] accessibility, avail‑ health facilities Medicines Global fund and flexible outlets were chased under for those buying ability and afford‑ and malaria Facility‑malaria business hours unlicensed the AMFm drugs at week‑ ability of ACT medicine retail‑ of retail facili‑ ‑Frequent stock‑ programme ends from private ers, including ties outs in public cost 40% outlets private clinics, facilities less than chemists, non‑AMFm pharmacies brands and other specialized drug stores K oduah et al. Systematic Reviews (2022) 11:257 Page 15 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Steyn, et al. South Africa To determine A retrospective Private sector Reference‑ N/A ‑Manufacturers N/A 1997 Medicine N/A The average Prescribing 2007 [43] the influence drug utilisation healthcare based pricing ‑Wholesalers and Related cost of frequency of of implement‑ study con‑ system (single ‑Retailers Substances antidiabetic antidiabetic ing SEP on the ducted in 2005 exit price). ‑Government Amendment medicine on medicine showed prescribing preva‑ and/or 2006 Act the database an increase lence and cost decreased of antidiabetic from the pre‑ medicine SEP period and interim period in the post‑SEP period Tougher, et al. Ghana, To examine the Quantitative, Retail outlets Affordable N/A N/A N/A ‑Already Lack of standard‑ Prices reduced N/A 2014 [62] Kenya, Mada‑ potential for price survey Medicines existing ACT ized mark‑ups for in most gascar, Niger, further reductions Facility subsidy policy retail pharmacy countries Nigeria, in the prices ‑malaria ‑Accessibility Tanzania of subsidized (AMFm) of private retail medicines facilities Koduah et al. Systematic Reviews (2022) 11:257 Page 16 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Tran et al. 2020 Kenya To describe how Retrospective Inventory Revolving fund Donations Kenya N/A Kenya MOH, Transportation N/A The availability of [42] the evolution study using audit reports, pharmacy or purchase MOH local leader‑ costs to health essential medi‑ of the RFP administrative essential CVD model sold at a small Health facilities ship and facil‑ facilities, oppor‑ cines improved programme data medicines list mark‑up price [community), ity administra‑ tunity cost of from an average increased access sufficient to level 2 (health tors’ effort to missed work and of 30–40% to > to essential CVD replenish drug dispensaries), integrate CVD distance from 90%, 18. In the medications for stock and level 3 (health and diabetes health facilities period of the patients across ensure sustain‑ centres), level clinical services Significant oper‑ current analysis different levels of ability 4 (subcounty as well as ating costs associ‑ (2018), this model the public sector hospitals), essential ated with running was run in 15 healthcare system level 5 (county medications the pharmacies facilities within in western Kenya hospitals), to into the lower including staff, the AMPATH level 6 (tertiary primary care‑ co‑pay waivers, catchment area referral hospi‑ level facilities supervisory audits Most tracer tals)] Creation of and transporta‑ medicines were local adoption tion of medicines present 94–100% mechanisms and supervisors of the time at Early engage‑ Patient volumes health facilities ment of key at each of these across levels 2–6 stakeholders lower‑level facili‑ (the availability of Developing ties were not suf‑ insulin (Humulin affordable ficient to sustain 70/30) at levels patient co‑ a full RFP 5 and 6 was pays, waivers Clinical officers or 97% and 100%, and account‑ nurses were too respectively, and ability mecha‑ overwhelmed 81–85% at levels nisms through to dispense and 2–4) inventory, maintain the An increase in financial and inventory of RFP the availability accounting medicines of generic CVD systems medications from the historical 30% or less to 90% or higher across all levels of the health system K oduah et al. Systematic Reviews (2022) 11:257 Page 17 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Walwyn and South Africa To evaluate Concurrent Quantiative Public‑private N/A National N/A ‑Uninter‑ Slow establish‑ Biovac Insti‑ No interruption Nkolele, 2018 whether private‑ mixed meth‑ — prices from partnership Treasury, rupted/reliable ment of a vaccine tute has been in the supply of [63] public partner‑ ods secondary (PPP) policy for Department of supply chain manufacturing successful in vaccines to any ship (PPP) of the sources vaccine pro‑ Health, Tech‑ ‑Political sup‑ centre containing location in the Biovac Institute Qualita‑ curement and nology Innova‑ port for PPP Forex fluctuation the cost of country provided value for tive — ‘key distribution tion Agency, (depreciation of procurement money for vac‑ stakeholders’ Industrial the local currency for the EPI cine procurement representa‑ Development vaccines, and distribution tives from BI, Corporation, and that this over the period National Treas‑ Departments competence 2010–2016 ury, National of Science & has been Department of Technology strengthened Health (NDoH), and Trade & over the provincial Industry period of this departments study of health, the The margin Technology averaged at Innovation approximately Agency, the 13%, cor‑ Industrial responding to Development a total value Corporation, of US $85.7 the Depart‑ million over ment of the period of Science and the evaluation Technol‑ or about US ogy and the $17million per Department year of Trade and Industry were invited; of these, 5 agreed to be interviewed Koduah et al. Systematic Reviews (2022) 11:257 Page 18 of 27 Table 2 (continued) Citation Geographic Objective/study Study design/ Study Medicine Implementation of medicine pricing Key influencers on Policy effects focus description type population pricing policy policies implementation and sample studied size Approaches Actors Use of Facilitators Barriers Effect on Effect on access evidence prices of to essential medicines medicines Wiedenmayer, Tanzania To develop a Baseline survey National Jazia prime Engaging one ‑Private sector N/A ‑Partnership Delayed payment N/A Tracer medicines 2019 [64] successful pilot of and M&E Coordination vendor system private sector ‑Government with private by the districts for availability in the a prime vendor reports Committee (public‑private pharmaceuti‑ ‑Medical stores sector their PV consign‑ region (mean system with the was formed, partnership) cal supplier department ‑Culture of ments (up to 90 availability of potential for composed as the prime ‑Health facili‑ transparency days) all districts) national scale‑up. of members vendor to ties and account‑ increased from from ministries provide the ‑National ability 69% in 2014 to and agencies. complemen‑ Coordination ‑Regional 94% in 2018 Regional tary medicines Committee leadership and district needed by stakeholders public health and health care facilities in workers Tanzania Wilson, 2012 Tanzania To assess the Mixed‑meth‑ Representa‑ Generics and N/A Tanzania N/A Existing ‑Lack of a N/A N/A [65] manufactur‑ ods case study: tives from domestic Pharmaceuti‑ international coherent policy ing capacity to quantitative government production cal Industries polices strategy for the produce ARVs data from doc‑ agencies, the policy (TRIPS Government supporting development of locally ument review, pharmaceutical and Doha domestic its pharmaceuti‑ qualitative data industry and Declaration) production of cals industry from semi‑ international, drugs ‑Weak patent structured bilateral enforcement interviews and organizations ‑High costs of document and NGOs importing sup‑ review plies Ye, 2015 [66] Ghana and To assess the Cross‑sectional Data collected Affordable N/A ‑Government N/A ‑Available Remoteness of ‑In Ghana, Medicines were Kenya availability, price from drug out‑ Medicines ‑Global fund funding to private outlets the prices in available in both and market share lets in Kenya Facility subsidize the remote and Kenya and Ghana of quality‑assured and Ghana ‑malaria drugs on a non‑remote artemisinin‑based global level areas did not combination ‑Reliable differ public therapy in remote distribution health facili‑ areas compared systems ties with non‑remote ‑Community ‑In Kenya, pri‑ areas at end line awareness vate for‑profit of the AMFm outlets in intervention remote areas were selling QAACT at nearly twice the price as in non‑remote areas Koduah et al. Systematic Reviews (2022) 11:257 Page 19 of 27 Table 3 Distribution of medicine pricing policies according to implementation countries Domains Specific medicine pricing policy Country Reference Targeted public subsidies Affordable Medicines Facility for Uganda, Tanzania, Kenya, Ghana, Fink, 2014 [41], Sabot 2009 [38], malaria Nigeria, Niger, Madagascar Smith, 2011 [37], Tougher 2014 [62], Ye 2015 [66] Free medicines scheme Cameroon, Mali d’ Almeida 2011 [47], Ponsar 2011 [39] Equity fund Madagascar Honda 2013 [53] Subsidy schemes Tanzania, Uganda, Senegal Ponsar 2011 [39] & Tougher 2014 [62] Regulatory framework and direct State price regulation frameworks Angola, Botswana, Democratic Liu 2017 [54], Maiga 2010 [55] price control Republic of Congo, Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Mali, Tanzania, Zambia and Zimbabwe Reference‑based pricing systems South Africa Casar & Suleman 2019 [50], de Jager & Suleman 2019 [44], Rothberg 2004 [61], Steyn 2007 [43] Single exit price (SEP) policies South Africa Steyn 2007 [43], Moodley & Sule‑ man 2019a [57] and Moodley and Suleman 2019b [58], Bangalee and Suleman 2016 [45], Bangalee and Suleman 2019 [46] Pharmacy and Poisons Act Sudan Ali and Yahia 2012 [36] Reimbursement schemes Ghana Ashigbie 2016 [49] Generic medicine pricing policies Generic medicine pricing policies South Africa, Mali, Kenya Bangalee and Suleman 2016 [45], Bangalee and Suleman 2019 [46], de Jager and Suleman 2019 [44], Maïga 2010 [55], Nicolosi 2009 [59], Onga‑ rora 2019 [60] and Wilson 2012 [65] Cost recovery and generics Mali Maïga 2003 [56] Purchasing policies Public‑private partnership South Africa, Tanzania Walwyn 2018 [63], Wiedenmayer 2019 [64] Revolving drug fund policy Sudan, Kenya Ali, 2009 [48] and Tran et al. 2020 [42] included studies due to limited information. For example, Types of medicine pricing policies implemented in SSA little or no information was provided on how potential con- The 31 articles identified in the review revealed a total founding factors were identified and dealt with to minimize of 13 medicine pricing policies were implemented bias. There was information on the follow-up period in one across SSA countries between 2003 and 2020. These out of the 3 studies reported. Follow-up was completed for policies represent four domains, shown in Table 3: (1) only one study, and strategies to address incomplete targeted public subsidies, (2) regulatory framework and follow-ups were not utilized. Measurement of exposures direct price control, (3) generic medicine policies and was not done uniformly across both exposed and unexposed (4) purchasing policies. populations; thus, the risk of bias was unclear. Statistical Medicine pricing policies were reported from 22/46 analyses adopted in the studies were relevant and reported countries in SSA, with 11 of the 31 studies reported results addressing the study objectives. Overall, on the from South Africa [46, 50, 54, 57–59, 61–64, 66]. As cohort studies, there was limited information to sufficiently shown in Fig. 2, most were single-country studies, but a appraise the studies, thus further increasing ambiguity and few were based on a multicountry data [51, 55, 59]. risk of bias of the included studies. Some studies focused exclusively on evaluating effects of a medicine pricing policy on access to healthcare [48, Medicine pricing policies implemented in sub‑Saharan 58, 60], the effect of the policy on prevailing prices of Africa medicines [39, 50, 52–55, 59, 61, 62, 66]. Others, how- In this section, we report results based on the four review ever, evaluated policy effects on medicine prices and questions. access to medicines [40–44, 46, 47, 49, 51, 56, 64, 65, 67]. Koduah et al. Systematic Reviews (2022) 11:257 Page 20 of 27 Fig. 2 Distribution of selected studies per countries in SSA How medicine pricing policies were implemented? studies [56, 58, 60] were described using private dis- tribution outlets and networks to improve financial Approaches to policy implementation Approaches to and geographical access of medicines through pooled policy implementation were described in 10/31 stud- procurement and subsided schemes. For example, in ies. Two main implementation approaches for medi- Tanzania, the government engaged private sector phar- cine pricing policies were evident in the data: (a) use maceutical supplier as the prime vendor to provide of private distribution outlets and networks and (b) complementary medicines needed by public health use of government’s regulatory frameworks. Three facilities [60]. K oduah et al. Systematic Reviews (2022) 11:257 Page 21 of 27 Table 4 Key facilitators and barriers to implementation of medicines pricing policies Facilitators Barriers Micro level factors Knowledge of implementation status (Honda 2013, Cohen Long‑distance travel by individuals (Ye 2015, Tran et al. 2020) 2013 and Maiga 2010) [51, 53, 55] [42, 66] Village with a drug shop (Smith 2011) [37] Alternative drugs that are less effective but cheaper preferred by public (Cohen 2013) [51] Meso level factors Drug and therapeutic committee to regulate prices at the Limited access to medicines, frequent stock outs (Fink 2014, facility level (Ashigbie 2016) [49] Honda 2013, Ye 2015, Smith 2011) [37, 41, 53, 66] Pooling resources and buying in bulk (Ashigbie 2016) [49] Shortage of trained personnel and lack of resources to scrutinize prices of medicines and information about medicine prices by the pharmaceutical companies (Ali and Yahia 2012, Tran et al. 2020) [36, 42] Lower prices increase access (Cohen 2013) [51] Lack transparency of prices in an external reference pricing (ERP) comparison where confidential discounts are negotiated (Cassar & Suleman 2019) [50] Subsidies/free provision of medicines (Ponsar 2011) [39] Lack of printed retail prices on medicine pack (Ali and Yahia 2012) [36] Macro level factors Existing national medicine pricing policies (Steyn 2007, Ashig‑ Lack of state capacity to regulate (Ali and Yahia 2012) [36] bie 2016) [43, 49] Strong political will from government (Walwyn & Nkolele Delays in reimbursement of health facilities and supplies (Ashig‑ 2018, Wiedenmayer 2019, Tran et al. 2020) [42, 63, 64] bie 2016) [49] Donor agencies and international policies and interventions Lack of scrutiny on medicine pricing policy by regulators (Ali (Wilson 2012, Ye 2015, Sabot 2009, Ali 2009) [38, 48, 65, 66] and Yahia 2012) [36] Lack of a coherent and well‑functioning national medicine pric‑ ing policy (Wilson 2012) [65] Use of essential medicines list (Ashigbie 2016) [49], Medicine Forex fluctuation (depreciation of the local currency) (Walwyn and Related Substance Amendment Act (Steyn 2007) [43] 2018) [63] Unfavourable reimbursement practices (Ashigbie 2016) [49] The second approach involved the use of regulatory Evidence to inform policy implementation None of frameworks to guide the sale and distribution of medi- the studies reported on the use of evidence to inform cines [39, 52, 54, 57, 62, 65, 67]. Seven reported on the implementation as well as monitoring and evaluat- use of regulatory frameworks. Reduction in reference ing implemented policies, although few studies (2/31) price was an approach used to set price ceilings for a par- explicitly described evidence use in informing the ticular group or category of medicines including generic design of medicine pricing policies. Where it was medicines [62]. The implementation of the single exit reported, evidence was sourced from review of phar- price (a fixed ex-factory price) policy was also observed maceutical pricing policies [48] and a WHO report in different contexts [46, 50, 54, 57, 61]. on medicine access and procurement of medical com- modities [64]. Actors in policy implementation A total of 22/31 stud- ies highlighted seven groups of policy actors who were involved in policy implementation. These comprised Key facilitators and barriers to implementation of medicine the following: government [40, 42, 43, 46, 47, 49, 51, 56, pricing policies 58, 60–62, 66, 68], wholesalers [39, 41, 46, 65], retailers Multiple contextual facilitators and barriers to the imple- [39, 41, 46, 47], manufacturers [39, 46, 50, 65, 68], donor mentation of the medicine pricing policies in sub-Saharan agencies [40, 42, 44, 49, 51], professional bodies [47, 52], Africa were identified in this review. These were across community members [56] and public and private health the micro (individual), meso (organizational) and macro facilities [43, 52, 60, 65, 67]. Information reported in the (national) levels (Table  4). Five studies only reported studies covered largely actors’ roles in policy implemen- facilitators [43, 46, 49, 54, 59], six reported only barriers tation, but did not report actors’ interests, agendas and [39, 44, 47, 53, 57, 62] and 14 reported both barriers and relative powers. facilitators [40–43, 45, 48, 51, 55, 56, 58, 60, 64, 66–68]. Koduah et al. Systematic Reviews (2022) 11:257 Page 22 of 27 Micro level factors Three studies cited education and reduction in the prices of medicines. The results of the awareness creation where prescribers and users were review showed that implementation of the tiered pric- aware of the medicines and therapies under the new ing (segmented pricing based on targeted markets), vol- medicine pricing policy as facilitators of successful untary licensing (removing of regulatory barriers) and medicine pricing policies [43, 48, 56]. A key barrier to generic policy (promoting prescribing generic medicines) implementation of medicine pricing policies was the in seven different countries across Africa led to reduc- long distance travelled by individuals in order to access tions in generic direct-acting antivirals (DAA) from US medicines [45, 51]. $1200 to between US $684 and US $750, i.e. the generic medicines were 40% cheaper than the originator prices Meso level factors Introduction of government subsi- [39]. However, some medicine pricing policies did not dies and exemptions of generic medicines contributed change much or appear to influence the prevailing medi- to a decline in the prices of medicines at facility level cine prices following implementation [50]. Although in Mali [42]. Pooling resources and buying in bulk also one of the goals of the Pharmacy and Poisons Act (2001) reduced the prices of medicines in Ghana [67]. Shortage implemented in Sudan was to control prices of the medi- of trained personnel and resources to assess and scruti- cines through regulating mark-ups along the supply nize prices of medicines and lack of information about chain, the evidence generated revealed that the policy did medicine prices by the pharmaceutical companies in not appear to have an effect in the prevailing medicine Sudan [39], and limited access to medicines and frequent prices [39]. stockouts in multiple countries [40, 44, 51, 56], were the main barriers reported. Effects on improved access to medicines Fifteen studies reported evidence of policy effect on improved availabil- Macro level factors The review showed that the use of ity and affordability to essential medicines [40–49, 51, national essential medicine lists by health facilities was 56, 60, 65, 69]. In Kenya, implementation of a revolving a facilitator of the implementation of reimbursement fund pharmacy model improved the availability of essen- schemes in Ghana [67]. Other facilitators were funding tial medicines from 30 to 40% to over 90% in 15 health support from donor agencies [41, 49, 51], international facilities [45]. In South Africa, when generic reference policy interventions such as supporting domestic pro- pricing was implemented, the use of generic rosuvastatin duction of medicines [68] and existing national essen- increased from 24 to 63.9% in the subsequent year and to tial medicines list and medicine and related substance 76.4% a year later [47]. In their assessment of the use of amendment Act [46, 67]. Challenges to implementation artemisinin combination therapy for malaria across dif- included lack of scrutiny on medicines pricing infor- ferent households in Tanzania, the researchers found that mation by regulators with medicine prices of certain artemisinin-based combination treatments increased generics higher than their originators [39]. Additionally, availability within the retail sector from 31 to 49% and unfavourable National Health Insurance Scheme reim- then to 61% [48]. bursement practices such as reimbursement delays and lack of price ‘mark-up’ standardization [67], and the lack of a coherent and well-functioning national medicine Discussion pricing policy, constrain efforts to regulate and ensure This systematic review sought to identify medicines better prices for improved access [68]. pricing policies implemented in SSA, how these were implemented, which contextual facilitators and barriers affected policy implementation and how effective were Effectiveness of implementing medicine pricing policies these policies. The review revealed 13 different medicine Medicine pricing policies sought to achieve two main pricing policies reflecting four domains, targeted public aims: (a) control or reduce the prices of medicines and subsidies, regulatory framework and direct price con- (b) improve access to essential medicines. Some studies trol, generic medicine policies and purchasing policies, reported separate effects on medicine prices [50, 53–55, were implemented across SSA between 2003 and 2020. 57, 59, 61, 62, 66] or improved access to essential medi- The medicines pricing policies were implemented in less cines [45, 48, 58, 60]. However, as shown in Table 2, many than half (22/46) of SSA countries. The main implemen- studies reported on both effects [40–44, 46, 47, 49, 51, 56, tation approaches involved the use of regulatory frame- 64, 65, 67]. works and private distribution outlets and networks. The review showed key actors involved in policy implemen- Effect on prices of medicines Overall, implementation of tation were government, wholesalers, manufacturers, the different medicine pricing policies largely suggests a retailers, professional bodies, community members and K oduah et al. Systematic Reviews (2022) 11:257 Page 23 of 27 private and public health facilities. The use of evidence to policy implementation [80–83]. This highlights one out- inform policy implementation was not reported in any of standing gap in the published knowledge on the imple- the included studies. Key barriers to policy implementa- mentation of medicine pricing policies, thus representing tion identified included limited awareness about policies, agenda for further research. frequent stock out, lack of capacity to regulate imple- The review showed slightly more reported barriers than mentation and lack of price transparency in external ref- facilitators to implementation of medicine pricing poli- erence pricing process, whereas key facilitators included cies. This may reflect researchers’ bias in revealing more existing national essential medicine policy environment, constraints in their investigations [84, 85], though this strong political will and support from development part- may also reflect a greater number of contextual inhibi- ners. Evidence on effectiveness of implemented policies tors to the implementation of medicines pricing policies on reducing prices and improving access to medicines in SSA contexts. The latter can be a particularly impor- was mixed. Reductions in prices were reported only in tant contribution to the field of health policy analysis and some studies. There was evidence that implementation of transferability of theoretical and practical lessons learned medicine pricing policy led to improved availability and to other health (and non-health) policies. affordability to essential medicines. The ultimate goal of medicine pricing policies is to The categories of medicine pricing policies identified in ensure low and affordable medicine prices as revealed this study are similar to what were previously reported, in our review. This finding is in line with another study which also highlight predominant focus on regulatory from Asia which found similar price reductions follow- measures or direct price control [70]. Although com- ing implementation of generic medicine pricing policy monly reported in SSA, regulatory measure or direct in Indonesia [86]. The authors reported that following control is considered highly contentious with no con- the implementation of the policy, the prices of lowest sensus in the literature. For example, opponents from price generic and innovator brands fell from 40 to 2200% the pharmaceutical sector advocate for a need for free between 2004 and 2010. A review of pharmaceutical pric- and open market systems, arguing that government ing policies in developing countries also revealed a simi- control undermines competition and innovation for lar outcome of reduced medicine pricing policies [70]. developing new drugs and limits access in the market to Some policies, however, did not have any effect on the address new medical conditions [71–73]. Weak systems prices of medicine [39, 54, 58]. For example, the intro- for government direct price control may not lead to the duction of a free medicines policy in Cameroon to pro- required outcome. As revealed in Sudan [39] and the vide free ART for people living with HIV appeared not to Philippines [74], regulation of medicine prices does not have achieved the goal of improving access to medicines. guarantee reduction in the prices of essential medicines It was reported that the policy resulted in shortages in and improved availability and affordability. It is therefore supplies, and as result, few patients were able to get the important to critically examine appropriateness of imple- second-line treatment. This was attributed to the fact mentation approaches for achieving outcomes within that the policy did not ensure that adequate systems and specific contexts. Adequate capacity to monitor and eval- infrastructure were in place to address increased demand uate policy implementation and understand contextual and avert resultant challenges impeding access to ARTs influences on the implementation is therefore critical. [58]. This is not new as previous studies revealed that the The use of generic medicines as a strategy to reduce implementation of generic medicine pricing policy in prices and ensure improved access was widely employed Europe resulted in higher prices, but higher prices also in SSA, and the effect on price and expenditure favours stimulated competition between generic medicines lead- the use of quality-assured generic medicines [8]. A review ing to prices reduction [75]. of generic medicine pricing policies in Europe revealed Implementation of medicine pricing policies can be that policies for implementing generic medicines used mediated by different contextual facilitators or barriers. different implementation mechanisms such as reduc- Our review has highlighted that key contextual barriers tions in reference prices and prescription status of medi- comprised weak enforcement or regulatory mechanisms, cines [75]. In our review, we found similar approaches for the absence of essential medicines list and the role of for- generic medicine policy and regulatory frameworks. eign exchange currency fluctuations. On the other hand, Although information on the role of actors was pro- facilitators included raising awareness about implemen- vided in the studies reviewed, the actors’ interests, agen- tation, existence of subsidies, use of essential medicine das, relative powers and networking arrangements such lists, establishing a fixed profit margin or percentage for as alliance building were missing. This information can manufacturers and the pivotal roles of supportive donor be revealed through stakeholder analyses [76–79] and is agencies and international policies and interventions. A often critical to form a comprehensive understanding of study in China also revealed contextual barriers such as Koduah et al. Systematic Reviews (2022) 11:257 Page 24 of 27 lack of enforcement of pricing regulations and policies, (for profit) sector plays a major role in pharmaceutical with authors encouraging strong governance structures manufacturing and distribution, but it is also important and legal frameworks to ensure enforcement [87]. The to encourage participation of underrepresented not-for- monitoring and enforcement of medicines pricing frame- profit groups such as civil society organizations, in health works need to be supported by well-trained and skilled policy processes. Third, it is important to continuously personnel, which is often lacking in different SSA coun- monitor and evaluate the implementation approaches tries [39, 53]. and emerging effects of these policies, something which This study also reported on the effectiveness of the our review observed was generally lacking. This can medicine pricing policies in SSA. Our review showed represent an opportunity for enhancing the culture of that some medicine pricing policies have the poten- evidence-informed decision-making within government tial to improve access to essential medicines [40–49, 56, agencies, as well as closer partnerships between govern- 60, 65, 69, 88], control or reduce the prices of essential ment agencies and research organizations. medicines [50, 53, 54, 57, 59, 61, 62, 66, 89] or have dual We call for more research on medicine pricing policy impact of improved access and controlled price effects implementation, covering three areas. First, more stud- [40–44, 46, 47, 49, 56, 64, 65, 67, 88]. However, evidence ies need to examine the role of evidence in the design on the impact of the medicine pricing policies should be and implementation of medicines pricing policies. The carefully interpreted as most of the studies were from increased interest and attention on evidence-informed nonexperimental or controlled studies, largely cross-sec- policy and planning decisions [90, 92–95] can sustain tional studies, e.g. [40–44]. Although a diversity of study the momentum, and it is important to strengthen capac- designs was included in the review, which were primar- ity within mainstream information systems to gener- ily nonexperimental in design, the findings still provide ate robust evidence rather than continuously rely on developing and potential evidence of impact following one-off and ‘external’ assessments [90, 93, 96]. Second, the implementation of the different medicine pricing future research on the role of policy actors involved in policies. the policy design process is critical for improving policy The findings from this review contribute to the field implementation, particularly covering actors’ interests, of policy analysis. Specifically, the taxonomies of the agendas, powers and resultant influences [80–83]. Third, categories of policies (i.e. targeted public subsidies, it is critical to generate robust evidence on key contex- regulatory framework and direct price control, generic tual influences on policy implementation and understand medicine policy and purchasing policies) and actor how individual factors can facilitate or constrain imple- groups (e.g. government, community members) involved mentation in different settings [97–100]. in implementation and the distinction of micro, meso and macro levels context, which mirrors other policy Study limitations studies [8, 9, 70, 90, 91]. We acknowledge the following limitations. First, the review focused on studies conducted in SSA, but Implications for policy and future research we acknowledge variation in income status, socio- This review suggests three implications for improving economic contexts and healthcare systems across implementation of medicine pricing policies in SSA, countries. Different contexts inevitably affected how which can also be applied to other health policies in medicine pricing policies were implemented and their LMICs more generally. First, four broad groups of pol- outcomes. As a result, we were guided by the generally icy options are available for reducing medicine pricing: limited contextual information included in the reviewed targeted public subsidies, regulatory frameworks and studies and resisted making too many assumptions direct price controls, generic medicine policies and pur- and inferences based on our knowledge of the differ- chasing policies. However, it is important to design and ent countries. We also suggest that experimental stud- apply the country-specific implementation mechanisms ies could report more robust and less biased results, as to avoid a ‘one-size-fits-all’ approach. Second, different compared to the reported studies in this review which stakeholders from both the public and private sectors can were largely cross-sectional with limited follow-up. play important roles in the design and implementation Second, we conducted comprehensive searches in a of medicine pricing policies. Inclusive policy processes range of health science, global health and multidisci- which allow representation of multiple voices of policy plinary databases to capture all SSA medicines pric- actors are, therefore, imperative to ensure sustainability ing literature, and although we may have missed some of policy implementation, pooling of resources and col- potentially relevant studies by not including specific lective ownership and acceptance. This is particularly pharmaceutical databases such as International Phar- pertinent to medicines pricing, given that the private maceutical Abstracts, we believe that full articles of K oduah et al. Systematic Reviews (2022) 11:257 Page 25 of 27 most of these abstracts would have been captured from Funding at least one of the databases, and this omission is not This research was commissioned by the National Institute for Health Research (NIHR) Global Health Policy and Systems Research Programme using UK aid expected to miss studies that could likely change the from the UK government (grant number 130219). The views expressed in this magnitude, direction or conclusions of this review. publication are those of the authors and not necessarily those of the NIHR or Third, given the different study designs employed, sam- Department of Health and Social Care. ple sizes and outcome measures, we faced a challenge Availability of data and materials to analytically compare the outcomes or effects of the All data generated or analysed during this study are included in this published policies on the prices and access to essential medicines. article. This notwithstanding, we feel our analysis provides a useful taxonomy of types of medicines pricing policies Declarations and highlights implementation approaches to inform Ethics approval and consent to participate future policy, practice and research. No ethics approval was required for this systematic review. Consent for publication Not applicable as the review does not contain any individual person’s data in Conclusion any form which requires consent for publication. The implementation of medicine pricing policies in SSA Competing interests focused on four policy options: targeted public subsidies, The authors declare that they have no competing interests. regulatory framework and direct price control, generic medicine policies and purchasing policies. Implementa- Author details1 Department of Pharmacy Practice and Clinical Pharmacy, School of Phar‑ tion of these policies in SSA shows some mixed evidence macy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana. of improved availability and affordability to essential 2 Department of Health Policy, Planning & Management, School of Public medicines, and it is important to understand country- Health, College of Health Sciences, University of Ghana, Legon, Accra, Ghana. 3 Department of Global Health and Development, London School of Hygiene specific experiences, diversity of policy actors and con- and Tropical Medicine, London, UK. 4 Department of Epidemiology and Dis‑ textual barriers and facilitators to policy implementation. ease Control, School of Public Health, College of Health Sciences, University 5 Our study suggests three policy implications for improv- of Ghana, Legon, Accra, Ghana. Ghana Health Service/Ghana College of Physicians and Surgeons, Accra, Ghana. 6 Leeds Institute of Health Sciences, ing implementation of medicines pricing policies in SSA: University of Leeds, Leeds, UK. 7 Nuffield Centre for International Health, Uni‑ avoiding ‘one-size-fits-all’ approach, engaging both pri- versity of Leeds, Leeds, UK. vate and public sector policy actors in policy implemen- Received: 23 November 2021 Accepted: 2 November 2022 tation and continuously monitoring implementation and effects of policies. Future studies can usefully examine interests, influences, relative powers and coalition forma- tion of policy actors during implementation of medicine References pricing policies. 1. Parker‑Lue S, Santoro M, Koski G. The Ethics and economics of pharma‑ ceutical pricing. Annu Rev Pharmacol Toxicol. 2015;55:191–206. 2. Vogler S, Paris V, Ferrario A, Wirtz VJ, de Joncheere K, Schneider P, et al. 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