Barriers to accessing essential medicines for kidney disease in low- and lower middle–income countries|

Abstract

Essential medicines are defined as those that “satisfy the priority health care needs of the population” and selected with due regard to public health relevance based on their efficacy, safety, and comparative cost-effectiveness.1World Health Organization The Selection and Use of Essential Medicines. Report of the WHO Expert Committee (Including the 12th Model List of Essential Medicines). WHO, 2003Google Scholar They are intended to be accessible within the context of functioning health systems in adequate quantities, in the appropriate dosage forms, with ensured quality and adequate information, and at a price the individual and the community can afford. The World Health Organization calls for “improved access to essential, high-quality, safe, effective and affordable medicines and health products.”2Chan M. Ten Years in Public Health2007–2017—Report by Dr Margaret Chan, Director-General—Access to Medicines: Making Market Forces Serve the Poor. WHO, 2017Google Scholar However, nearly 2 billion people have no access to essential medicines globally, particularly in low-income countries (LICs) and lower middle–income countries (LMICs).2Chan M. Ten Years in Public Health2007–2017—Report by Dr Margaret Chan, Director-General—Access to Medicines: Making Market Forces Serve the Poor. WHO, 2017Google Scholar In the case of chronic kidney disease (CKD), essential medicines as defined previously by the International Society of Nephrology (ISN) are antihypertensives, statins, anemia medications, CKD– mineral bone disease medicines, potassium-lowering agents, and steroids.3International Society of NephrologyISN Framework for Developing Dialysis Programs in Low-Resource Settings 2021.https://www.theisn.org/wp-content/uploads/2021/03/ISN-Framework-Dialysis-Report-HIRES.pdfDate accessed: January 3, 2022Google Scholar Their access is vital to reduce the risk of kidney failure, particularly because kidney replacement therapy is cost-prohibitive in many regions of the world, and they are critical to the success of programs aimed at early identification and management of CKD. The Emerging Leaders Program cohort 1 of the ISN used a web-based survey of health care workers (HCWs) to explore barriers to access to essential medicines in LICs and LMICs for people with CKD. Secondary objectives were to quantify access, explore solutions, and to compare access and barriers across health care settings. (See Supplementary Methods for full details.) There were 213 respondents from 39 countries (of 50 contacted by the ISN), including 14 LICs (of 24 LICs) with 33 respondents (15%) and 25 LMICs (of 47 LMICs) with 180 respondents (85%; Supplementary Table S1). The respondents were mostly from Africa (14 LICs, 12 LMICs) and Asia (9 LMICs) with 4 other LMICs from Central Europe and Central or South America. Participants were mainly HCWs in tertiary settings (165 of 213, 78%). Access to essential kidney medications decreased dramatically from tertiary to community settings (Figure 1, Supplementary Table S2). In tertiary settings, on average 74% of respondents (SD 8.8%) felt that essential kidney medications were mostly accessible. They included essential anemia (oral iron 83%, erythropoietin/analogues 79%), hypertension (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers [ACEis/ARBs] 85%, diuretics 83%), cardiology (aspirin 83%, statins 81%) and diabetes (metformin 83%, insulin 80%) medications, and prednisone (82%). There was poorer access to non-calcium–based phosphate binders (57%), sodium bicarbonate (66%), and non-prednisone–based glomerulonephritis treatments (63%). In contrast, in community settings there was poor access to all essential kidney medications (31% mostly accessible, SD 19.9%). Oral iron (61%) and diuretics (57%) were more accessible than other classes, but i.v. iron (11%), erythropoietin/analogues (8%), ACEis/ARBs (37%), statins (21%), insulin (32%), phosphate binders (18%), sodium bicarbonate (16%), and prednisone (39%) were mostly inaccessible in community settings (Supplementary Table S2). Barriers related to resourcing and demand increased dramatically when moving from tertiary through to community health care settings (Figure 2 and Supplementary Tables S3 and S4). Around three-quarters of respondents felt that resourcing and logistics barriers commonly occurred in community settings, such as inefficient supply chain (73%), lack of storage facilities (82%), and scarcity of HCWs (83%). Drug issues also escalated in rural areas, including poor drug quality (83%) and limited supply of dispensed medications (75%). Lack of perceived demand also contributed to poor accessibility of essential medicines in the community. Respondents reported few patients with kidney disease presented to community centers (73%), with demand impacted by poor patient education (82%) and cultural/local/religious reasons (85%). In contrast, barriers related to national health policy were uniformly high throughout all health care settings. Around 70% of respondents identified lack of government funding for health care, poor health insurance coverage, kidney medications not included on the national list of essential medications, and lack of policies encouraging the use of generic medications as barriers to medication access across all health care settings. Potential interventions to improve access to kidney medications centered around improving affordability, promoting the use of quality medicines, and strengthening drug production and supply chains (Supplementary Figure S1). In particular, the respondents endorsed government interventions to improve affordability, including national financing of essential kidney medications (64%), incorporating medication coverage as part of private or public health insurance (52%), encouraging in-country production of generics (47%), and placing kidney medications on the national list of essential medications. A minority of respondents felt regulating the supply chain (25%), guiding quality medicines use through locally adapted treatment guidelines (27%), linking HCW incentives to patient adherence (14%), or involving informal rural medical providers (10%) could improve medication access. There were no differences in the ranking of responses between respondents from LICs and LMICs (P = 0.68) or between HCWs in community/regional settings and in tertiary setting (P = 0.59). In free text responses, survey respondents offered many further ideas to improve access to kidney medications, where thematic analysis revealed 4 main themes: (i) government funding; (ii) equitable distribution; (iii) regulation; and (iv) CKD education. Increasing government funding underpinned much of the approaches, such as direct funding for “medications . . . covered by the national insurance scheme” (tertiary HCWs, LMICs) and bolstering the health care system by “training more doctors and nurses” (tertiary HCWs, LICs). Respondents stressed the importance of equitable distribution of medications, suggesting a “robust supply chain mechanism at the state level to ensure distribution to the communities” (tertiary HCWs, LMICs) and ensuring “medications are . . . covered in . . . the community setting [so patients don’t have] to travel long distances” (other HCWs, LMICs). Strong regulation was recommended to optimize processes, including “ensuring proper quality of medication” (tertiary HCWs, LMICs) and “monitoring the availability and accessibility of essential medications” (tertiary HCWs, LICs). Targeting CKD “knowledge and awareness to CKD management” (tertiary HCWs, LICs) by “training local practitioners” (community HCWs, LMICs) could improve high-quality prescribing. There are over 750 million people globally who have kidney disease and poor access to a wide range of kidney health services for those in LICs and LMICs.4GBD 2015 DALYs and HALE CollaboratorsGlobal, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet. 2016; 388: 1603-1658Abstract Full Text Full Text PDF PubMed Scopus (1575) Google Scholar,5Crews D.C. Bello A.K. Saadi G. World Kidney Day Steering CommitteeBurden, access, and disparities in kidney disease.Kidney Med. 2019; 1: 6-12Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Access to essential medicines is vital to achieving health equity for the residents of LICs and LMICs and to achieving the United Nations Sustainable Development Goal 3 target of reducing premature mortality related to noncommunicable diseases by one-third by 2030.6Luyckx V.A. Tonelli M. Stanifer J.W. The global burden of kidney disease and the sustainable development goals.Bull World Health Organ. 2018; 96: 414-422DCrossref PubMed Scopus (439) Google Scholar,7NCD Countdown 2030 CollaboratorsNCD Countdown 2030: pathways to achieving Sustainable Development Goal target 3.4.Lancet. 2020; 396: 918-934Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar This survey revealed that access to essential kidney medicines was challenging in LICs and LMICs, particularly in community settings, where only 31% of respondents reported reasonable access to essential medications. Barriers to access relating to national health policy and funding were reported by over two-thirds of respondents, regardless of health care setting. In community settings, barriers relating to resourcing and demand were reported by over 70% of respondents. Potential interventions to improve access to kidney medications centered around improving affordability (especially through universal health care), promoting the quality use of medicines and strengthening drug production and supply chains. The lack of access to essential kidney medications, which can prevent CKD, decrease disease progression, or prevent complications of CKD, contributes to the discrepancies in years of life lost due to kidney disease between high-income countries and LICs.8Ke C. Liang J. Liu M. et al.Burden of chronic kidney disease and its risk-attributable burden in 137 low- and middle-income countries, 1990–2019: results from the Global Burden of Disease study 2019.BMC Nephrol. 2022; 23: 17Crossref PubMed Scopus (24) Google Scholar This multinational survey confirms prior reports of limited access in low-income settings to some essential kidney medicines from the ISN Global Kidney Health Atlas,9Bello A.K. Levin A. Lunney M. et al.Status of care for end stage kidney disease in countries and regions worldwide: international cross-sectional survey.BMJ. 2019; 367: l5873Crossref PubMed Scopus (121) Google Scholar such as sodium bicarbonate and potassium exchange resins, and extends prior knowledge by providing a granular description of access to a wide range of essential medications, stratified by health care setting. Around 80% of respondents reported vital medications such as antihypertensives (ACEis/ARBs), anemia medications (iron, erythropoietin analogues), and cardiovascular medications (e.g., statins, aspirin) could be accessed in tertiary health care settings. Management of advanced CKD was largely restricted to the tertiary setting and, even then, was hindered by poor access to sodium bicarbonate (66%), non-calcium–based phosphate binders (57%), and potassium exchange resins (56%). Given community health care settings are the entrance point to care for most, it is critical that medications to prevent CKD, slow progression of disease, and treat comorbidities are widely accessible here. Unfortunately, there was a clear gradient in the accessibility of kidney medicines from mostly accessible in tertiary health care settings (averaged 80% of respondents) to rarely accessible in community settings (averaged 31%). In the community setting, 37% of respondents stated ACEis were mostly accessible, similar to beta-blockers (42%), insulin (31%), and even lower for statins (21%). For most, glomerulonephritis treatment was limited to prednisone, with other treatments only reported as accessible in the tertiary setting by 63% of respondents and 7% in the community setting. This survey identified many barriers contributing to poor access to kidney medications, clustered around themes of resourcing, logistics, health policy, and cost. This aligns with previous reports of barriers to kidney replacement therapies.S1 Cost was a driver of barriers regardless of health care setting. Large out-of-pocket costs translate to huge individual financial burden. Around 188 million people have catastrophic health expenditures yearly in LMICs as a result of CKD.S2 Beyond cost, logistical, and resourcing barriers, particularly relating to medication supply chains, health care workforce shortages, and the ability to store and dispense medications impeded access, especially at a community level. High-income countries have on average 23.3 nephrologists per million population, compared to only 0.2 per million in LICs.S3 Resourcing issues extended beyond nephrologists, with 75% of respondents identifying limited dispensing of only a few days of medications as a barrier to access. Interestingly, 85% of respondents also reported cultural/religious reasons that medications were not used in community settings. Further research is needed to understand the reasons for this acceptability barrier. While 73% of respondents felt community centers had few patients with kidney disease, the inability to prevent CKD by attending to hypertension and diabetes is a missed opportunity. Solutions to improve access centered on affordability, policies regarding quality use of medicines, and strengthening supply chains. Improving government funding for medications was endorsed by 64% of respondents. While universal health coverage is necessary to achieve global kidney health equity,6Luyckx V.A. Tonelli M. Stanifer J.W. The global burden of kidney disease and the sustainable development goals.Bull World Health Organ. 2018; 96: 414-422DCrossref PubMed Scopus (439) Google Scholar budgetary constraints, exacerbated by coronavirus disease 2019, have an impact on governmental ability to fund medications. In addition, increasing funding for health care means the money needs to be pulled from other areas, likely impacting other important government services. It is important that cost-effective solutions for high-value medications are identified.S4 However, countries should prioritize supply of essential medicines, given that population health interlinks with all other Sustainable Development Goals. Moreover, essential kidney medicines identified by the ISN target multiple risk factors common to many noncommunicable diseases, so there are benefits beyond kidney disease that should be factored in health care spending decisions.S5 Generic formulations are available for these kidney medicines, and therefore implementing generic medicine policies can be effective at reducing costs. For new medicines (e.g., sodium-glucose linked transporter-2 inhibitors), health technology assessment should guide evidence-informed decision making for drug procurement within the limits of acceptability for jurisdictions/countries. Another important aspect to prioritize is the universal inclusion of essential medications (particularly those targeting more than 1 noncommunicable disease) on national essential medications lists. Local, regional, and international nephrology associations such as the ISN can drive advocacy initiatives to place essential kidney medicines on each nation’s essential medication list. Finally, lack of access in community settings was driven by sparse demand, poor supply and storage, and lack of specific kidney expertise in local HCWs. Potential solutions include government-funded transport of patients with more advanced CKD to tertiary centers where kidney medicines and comprehensive CKD care are accessible. In addition, monitoring and development of inventory management systems using information technology solutions can ensure supply chain integrity. Targeted education programs and medication distribution programs aimed at CKD prevention (blood pressure control, urine protein screening, diabetes control) could be rolled out at the community level involving primary HCWs to reach the wider population who are at risk of kidney disease. Limitations of this survey include few respondents from Central and South America, limiting generalizability of the findings to these regions. Other potential limitations include the lack of a formal qualitative interview process, lack of questions around transplantation medications, or new drug classes shown to prevent CKD progression (e.g., sodium-glucose linked transporter-2 inhibitors) and selection bias from targeting ISN members for the survey, who may be more clustered in tertiary settings along with ascertainment bias (e.g., only those with access to the Internet were able to respond). Access to quality kidney essential medicines in LICs and LMICs is poor outside of tertiary health care settings. Barriers are multifactorial. A concerted effort is needed to dismantle barriers to achieve equity in global kidney health.