Table 4.

Results of the scoping review. Evaluations of legal interventions for medicines financing and affordability in five middle income countries.

Article	Country	Study Design	Legal Intervention	Main Objectives of the Legal Intervention Studied (Definitions in Table 2)	Study Population & Data Source	Main Findings
1. Mena MB, 2020 [41]	Ecuador	Cross-sectional design describing characteristics of patient claiming government-funded access to cancer medicines in Ecuadorian courts. This study investigates the frequency of successful claims, the clinical eligibility of patients to receive the medicines they claim, the therapeutic monitoring of court-ordered medicines, and the potential budget impact of court-ordered medicines if extended to all eligible potential patients in Ecuador.	Constitution of the Republic of Ecuador. Asamblea Nacional de la Republica del Ecuador; 2008.	Health equity Sanctions & remedies	25 court claims (representing 33 patients with cancer) between 2012–2018 for government-funded cancer medicines. Data was collected from court decisions published on the official website of the Judicial System. Data from trial registration pages (National Library of Medicine, clintrials.gov) were used to assess whether the claimants fulfilled the clinical trials eligibility criteria. Therapeutic monitoring reports were sourced from the National Directorate of Medicines and Medical Devices. To estimate the potential budgetary impact administrative statistics from Ecuador were used. When they were not available, extrapolations to the Ecuadorian population were based on data from www.Orpha.net	97% of court claims (n = 32/33 court claims) involving the Ministry of Public Health for government-funded cancer medicines were granted between 2012–2018. 51.5% of patients did not meet the eligibility criteria used in key clinical trials demonstrating the efficacy of the requested medicine. Potential budgetary impact if medicine universalised to all patients who need; would consume 114.5% of Ecuador’s 2017 annual public pharmaceutical budget.
2. Eckhardt et al. 2019 [42]	Ecuador	Cross-sectional qualitative study to explore the perceived effects of the 2008 health reform implementation on rural primary health care services and financial access of the rural poor.	Constitution of the Republic of Ecuador. Asamblea Nacional de la Republica del Ecuador; 2008	Economic policies and regulation Health equity	Data was collected through focus group discussions with health staff, local health committee members, village leaders, and community health workers in a rural region of the province of Esmeraldas. Qualitative content analysis was applied and Walt and Gilson’s model for health policy analysis was used to interpret the results.	Obstacles in communication about the reform: 40–50% of villagers were aware that medicines are now free of charge; preconception that medicines in public sector are of unreliable quality; Increased demand for health care services: Reports of patients requesting medicines without being ill; Availability after the reform: more free medicines in the public system, but high patient loads sometimes caused competition for supply and shortages; Financial effects for the population: unconfirmed reports of free medicines being sold (not allowed).
3. WHO, 2019 [43]	Ukraine	Cross-sectional qualitative and quantitative design combined with a time series analysis of INN trends to assess whether the AMP had succeeded in fulfilling its objective to provide more patients with affordable medicines for selected chronic diseases (cardiovascular diseases, type 2 diabetes and bronchial asthma); and to evaluate possible uneven uptake of the programme across oblasts (geographic areas) and possible explanatory factors	Law on State Financial Guarantees of Health Care Services to the Population (2017)	Economic policies and regulation Health equity Infrastructure	Study population was the national pharmaceutical market, and local and national pharmaceutical stakeholders. Data sources were literature and legal documents, quantitative data from national and regional authorities and private companies about the pharmaceutical sector, and structured qualitative interviews with stakeholders. Data was collected from April-September 2018 for the period prior to and following the implementation of the 2017 law.	Accessibility: (a) >8 million Ukranians enrolled in/covered by the AMP; (b) 6–28 pharmacies per 100,000 inhabitants participated in the AMP, amounting to 40% of pharmacies in Ukraine; (c) variable but increased consumption of reimbursed medicines in all oblasts, ranging from from 8% to 50% in certain oblasts. Affordability: (a) 85% average reductions in patients’ co-payments; (b) prices decreased in all except one therapeutic area (bronchial asthma) covered by AMP; (c) budget allocation to AMP by the Ministry of Health was 21.8 million Eur in 2017 and 31 million Eur in 2018. Acceptability: No major complaints reported by pharmacies (regarding timely reimbursement by authorities) and patients (except that they must sometimes wait one day for their medicines). Efficiency: (a) INNs included in the AMP were 21 by April 2017 and 23 by end 2017; (b) Sales of medicines and their market share increased markedly after implementation. (c) No clear link between the AMP and the recently established Essential Medicines committee, nor is there a formal process for expanding the therapeutic areas covered by AMP.
4. Moodley et al., 2019 [44]	South Africa	Interrupted time series analysis, examined the impact of the in 2004 implemented Single Exit Price (SEP) intervention on private sector price data from a basket of generic medicines.	Act No. 101 of 1965 on Medicines and Related Substances Act, 1965 amended through 2002 Regulations for a transparent pricing system, 2004	Economic policies and regulation Information	Price data were obtained from pharmacy dispensing files, claims data and other routinely collected data for a basket of medicines (50 originator and their available generics). Data was obtained for the period December 1999-December 2014, corresponding to five years prior to the implementation of the SEP (1999–2003) and over the subsequent ten years (2004–2014).	Three trends were observed with different generics: (1) Medicine prices prior to 2004 showed a year-on-year steady rate of increase. The average rate of increase before the regulation was higher than the average rate of increase after the regulation. (2) Medicine prices were already decreasing prior to the intervention in 2004, and after intervention the medicine saw a price reduction (n = 28 generic medicines); (3) prices had a steady increase in price between 1999 to 2004 with a steep drop in 2004, which may be related to competition or stock issues (n = 3 generics).
5. Moodley et al., 2019 [45]	South Africa	Interrupted time series analysis evaluating the impact of the in 2004 implemented Single Exit Price (SEP) on the retail price of a basket of originator medicines.	Act No. 101 of 1965 on Medicines and Related Substances Act, 1965 amended through 2002 Regulations for a transparent pricing system, 2004	Economic policies and regulation Information	Private sector retail price of fifty originator medicines, based on WHO/HAI basket of medicines. Price data was obtained from pharmacy dispensing files, claims data, and other routinely collected data. Data was obtained for the period December 1999–December 2014.	“Most medicines investigated showed a smaller yearly increase in price compared to before regulations due to the controlled pricing environment introduced by Government.” Depending on which list the product appeared (global core, regional core, supplementary), the average price changed by 19.87% (SD 10.62%)–23.38% (SD 12.43%).
6. Kanmiki et al., 2019 [46]	Ghana	Longitudinal study examining changes in out-of-pocket payments vis-à-vis health insurance claims to investigate the impact of Ghana’s National Health Insurance Scheme (NHIS) on out-of-pocket healthcare payments (medicines, services, and obstetric care).	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012)	Economic policy & regulations Health equity	Revenue data for out-of-pocket payments and health insurance claims for unspecified medicines, services and obstetric care. Data was collected for the years 2010–2014 from public primary healthcare facilities in seven districts of the Upper East Region of northern Ghana.	Between 2010–2014, out-of-pocket payment for medications in primary healthcare reduced by 62% and health insurance claims for medicines increased by 34% (2013) and 9% (2014).
7. Durán et al. 2019 [47]	Ecuador	Interrupted time series analysis investigated the impact of two policies on the utilization of new targeted oncologic medicines in Ecuador.	National policy (April 2012) “allowing hospital drug and therapeutic committees (DTCs) to select and procure drugs not previously included in the NEML” Policy (April 2013), the core of the policy being “the requirement that any decision taken by hospital DTCs regarding selection of new drugs must be confirmed by the National Medicines Directorate, an administrative unit of the Ministry of Health”.	Economic policy & regulations Infrastructure	Patient dispensing data for twenty-three targeted oncologic medicines over five years (2010–2014). Data is draw from routinely collected data from the six largest Ecuadorian cancer hospitals (three private and three public).	“Transferring the responsibility to select new drugs to hospital drug and therapeutic committees produced an increase in prescription intensity of targeted oncologic drugs, mainly in the private sector.” The second policy intervention aimed to centralise these decisions in a single body (while still keeping the first level of decision making in hospitals) reduced the incidence of prescriptions of targeted expensive oncologic medicines.
8. Dalinjong et al., 2018 [48]	Ghana	Convergent parallel mixed methods design, using qualitative and quantitative data investigating whether the free maternal health policy under the National Health Insurance Scheme (NHIS), [36] introduced in 2008, eliminated out-of-pockets payments for maternal health services, including medicines.	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012). Implementing policy: Free maternal health policy (2008) under the NHIS.	Economic policy & regulations Health equity	406 women in the Kassena-Nankana municipality (rural area) who used pregnancy services, 25 midwives/nurses and 3 managers/directors. Data was collected through structured questionnaires (with women informants), 10 focus group discussions (with women informants), and in-depth interviews (with health providers and managers/directors). Data were collected in March-August 2016.	Half of women interviewed reported making direct out-of-pocket payments for medicines during pregnancy care. The average paid for medicines was US$18.10 (SD US$34.40).
9. Durán et al., 2018 [49]	Ecuador	Longitudinal study of hospital dispensing data examining utilization and expenditure trends of oncologic medicines (targeted, chemotherapy, hormonal) in 2010–2014.	Constitution of the Republic of Ecuador. Asamblea Nacional de la Republica del Ecuador; 2008.	Health equity	23 targeted oncologics, 43 chemotherapeutics, and 11 hormonal medicines prescribed to 40,099 between 2010 and 2014. 60.3% of patients were female. Data from three public and three private cancer centres in Ecuador, comprising the six largest Ecuadorian cancer hospitals in 2010–2014.	The proportion of patients using targeted medicines doubled in the period of 2010–2014, whilst the utilization of chemotherapy showed a downward trend, and the use of hormonal therapy remained stable with a dip in 2012. Total expenditures on cancer drugs more than doubled (by factor 2.3) in 5 years, although the total number of patients was rather stable through the period of analysis. The rising pattern is driven by the expenditures on targeted drugs.
10. Dalinjong et al., 2017 [50]	Ghana	Quantitative and qualitative convergent parallel mixed methods study, using structured questionnaires and focus group discussions estimating out-of-pocket payments and financial impact during childbirth under the free maternal care policy under the National Health Insurance Scheme (NHIS).	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012) Implementing policy: Free maternal care policy (2008) under the NHIS.	Economic policy & regulations Health equity	353 women (mean age 27 years) who gave birth in health facilities “in one rural and poor area of Northern Ghana; the Kassena-Nankana municipality.” Data were collected in March-August 2016.	91.8% of women incurred a mean out-of-pocket payment for medicines during childbirth of US$24.70.
11. Ashigbie et al., 2016 [51]	Ghana	Qualitative cross-sectional study of key informants, investigating the challenges of medicines management in the public and private sector under the National Health Insurance Scheme (NHIS).	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012)	Economic policy & regulations Health equity	Semi-structured interviews with 26 key informants purposively selected from public and private sector hospitals and standalone pharmacies (including mission hospitals), pharmaceutical supplies, and NHIS district offices in the Eastern, Greater Accra and Volta regions of Ghana, interviewed between July and August 2014.	Most informants “agreed that the introduction of the NHIS has increased access to and utilization of medicines by removing cost barriers for patients.” Common concerns include “delays in receiving NHIS reimbursements, and low reimbursement rates for medicines which result in providers asking patients to pay supplementary fees.” Differences between private and public sectors are weak separation of prescribing and dispensing and limited use of drugs and therapeutic committees in the private sector, the disproportionate effects of unfavourable reimbursement prices for medicines, and inadequate participation of the private sector providers (especially pharmacies and licensed chemical sellers) in the NHIS.”
12. Aryeetey et al., 2016 [52]	Ghana	Retrospective cross-sectional study investigating the effect of the National Health Insurance Scheme (NHIS) on the availability of essential medicines in mission health facilities.	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012)	Economic policy & regulations	Structured questionnaires and exit interviews gauging the availability of selected essential medicines in 34 mission facilities (hospitals, clinics, specialist centres, and (primary) health centres), grouped into the three ecological zones: 12 coastal (southern), 17 forest (middle) and 5 savannah (northern). Data were collected for the periods 2003 and 2010.	Availability of essential medicines in facilities generally improved after the introduction of the NHIS in all three ecological zones.
13. Espinosa MV, 2016 [53]	Ecuador	Pre-/post-intervention study of medicines ceiling prices of cardiovascular medicines after the implementation of a price control regulation.	Executive Decree no. 400. Regulation of medication price setting. 2014, modified 2017	Economic policy & regulations	364 cardiovascular medicines marketed in Ecuador’s private sector were included. Data was collected from administrative datasets. Pre-intervention sales prices were derived from the Ecuadorian Pharmacotherapeutic Formulary. Post-intervention sales prices were the ceiling prices set by the Ecuadorian Technical Secretariat for fixing prices.	There was no significant average change in the ceiling price of the 364 cardiovascular medicines with prices regulated under the Executive Decree no 400. However, the price of thiazides and loop diuretics increased by US$0.018 per unit (tablet) (p = 0.02), statins decreased by US$0.21/unit (p = 0.001), and angiotensin-converting enzyme inhibitors decreased by US$0.10/unit (p = 0.014) after the regulation took effect.
14. Kusi et al., 2015 [54]	Ghana	Cross-sectional representative household survey investigating the effect of the National Health Insurance Scheme (NHIS) on out-of-pocket health expenditures (OOPHE), comparing expenditures from insured and uninsured persons.	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012).	Economic policy & regulations Health equity	Out of pocket health expenditures of 1082 household members who reported sick in the last four weeks. (449 were uninsured, 633 were insured) Data was collected through a representative household survey from three districts in Ghana between February-April 2011.	The NHIS significantly decreased OOPHE, but with respect to the cost of prescribed drugs bought from outside the facility, paradoxically insured persons paid a higher amount (US$9.51) than uninsured persons (US$7.08), an observation for which the authors did not have an explanation.
15. De Guzman et al., 2014 [55]	Philippines	Qualitative cross-sectional study investigating the knowledge, attitudes, and practices with respect to the Cheaper Medicines Act (CMA) and the Government Mediated Access Price (GMAP) list, assessing the impact and implementation of the CMA among households	Republic Act 9502, “Universally accessible and quality medicines act of 2008 (“Cheaper Medicines Act of 2008”). Congress of thePhilippines,” 2008. Executive Order No 821 S, “Prescribing the maximum drug retail prices for selected drugs and medicines that address diseases that account for the leading causes of morbidity and mortality. Philippine Government, 2009.	Economic policies & regulation Information	62 female respondents residing in metro Manila from three socio-economic classes (SECs) participated in 9 focus group discussions conducted in June 2013. Participants were selected based on the Philippine Marketing and Opinion Research Society (MORES) classification and on their being household (HH) decision makers on health matters	“Across all SECs, there is low spontaneous awareness of the CMA although many [respondents are] spontaneously aware of the Generics Act.” “Across all SECs, mass media channels are main sources of awareness and information on the CMA. Government doctors and health centres are poor sources of information on the CMA but are very good sources of information and advice on generics especially among the lowest SEC. Private doctors are poor sources of information on the CMA and generics.” “Respondents across all SECs have not noticed the GMAP price list in drugstores. They also have not noticed price reductions in branded drugs-possibly because GMAP does not cover drugs they buy including those for common ailments.”
16. Sarol, Jr., 2014 [56]	Philippines	Cohort design study investigating the impacts of the maximum drug retail pricing (MDRP) policy and the government-mediated access prices (GMAP) policy, flowing from the “Cheaper Medicines Act” of 2008, on selected medicines molecules directly affected by the MDRP/GMAP polices.	Republic Act 9502, “Universally accessible and quality medicines act of 2008 (“Cheaper Medicines Act of 2008”). Congress of the Philippines,” 2008. Executive Order No 821 S, “Prescribing the maximum drug retail prices for selected drugs and medicines that address diseases that account for the leading causes of morbidity and mortality. Philippine Government, 2009.	Economic policies and regulation	Price data of eleven selected medicine molecules which were placed under MDRP/GMAP listing. Data was collected through independent surveys conducted by IMS Health Philippines from a stratified sample of 600 retail medicine stores in 2009 and 2011 each. Price data were obtained using a mystery shopper approach.	Ten of the 11 medicines significantly decreased in mean price by being listed as MDRP/GMAP reference drugs. However, the author concluded that the number of MDRP/GMAP listed medicines was very limited compared to the total list of essential medicines and the polices may not have had a tangible effect yet.
17. Nguyen et al., 2011 [57]	Ghana	Cross-sectional study evaluating the impact of the National Health Insurance Scheme (NHIS) on households’ out-of-pocket spending and catastrophic health expenditure two years after the introduction of NHIS	National Health Insurance Act, 2003. Act 650. Accra, Ghana. 2003 (revised to Act 852 in 2012)	Economic policy & regulations Health equity	Health expenditure data from a survey of 2500 households (11,617 persons in total, of which 6718 are NHIS non-members and 4899 are NHIS members). The survey was conducted in two rural districts, Nkoranza and Offinso, in September–October 2007.	NHIS members incurred out-of-pocket medicine payments that equaled 73% of those incurred by NHIS non-members. A ‘not trivial’ portion of these out-of-pocket payments were for medicines (among other services) that should be covered by insurance.