Universal health coverage and chronic conditions
Authors: Louis W Niessen, S Bertel Squire
Journal: The Lancet Global Health (2019)

The upcoming UN high-level meeting on universal health coverage in September, 2019, aims to provide a developmental framework for international and national agendas on universal prevention and treatment packages and financial protection.1UNMoving together to make the world a healthier place.https://www.un.org/pga/73/event/universal-health-coverage/Date accessed: August 15, 2019Google Scholar, 2UN Statistics DivisionThe Sustanability Development Goals report.https://unstats.un.org/sdgs/report/2019/The-Sustainable-Development-Goals-Report-2019.pdfDate: 2019Date accessed: August 18, 2019Google Scholar Universal coverage of prevention and treatment of chronic diseases is a relevant topic in view of rising non-communicable disease epidemics in the world's ageing populations.3Babar ZU Lessing C Mace C Bissell K The availability, pricing and affordability of three essential asthma medicines in 52 LMICs.Pharmacoeconomics. 2013; 31: 1063-1082Crossref PubMed Scopus (42) Google Scholar, 4Bateman ED Reddel HK O'Byrne PM et al.As-needed budesonide-formoterol versus maintenance budesonide in mild asthma.N Engl J Med. 2018; 378: 1877-1887Crossref PubMed Scopus (187) Google Scholar, 5Bazargani YT de Boer A Leufkens HG Mantel-Teeuwisse AK Selection of essential medicines for diabetes in low and middle income countries: a survey of 32 national essential medicines lists.PLoS One. 2014; 9e106072Crossref PubMed Scopus (17) Google Scholar, 6Beasley R Fingleton J Weatherall M Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma.Thorax. 2013; 68: 119-120Crossref PubMed Scopus (7) Google Scholar, 7Garrib A Birungi J Lesikari S et al.Integrated care for human immunodeficiency virus, diabetes and hypertension in Africa.Trans R Soc Trop Med Hyg. 2018; (published online Sept 28.)DOI:10.1093/trstmh/try098Crossref PubMed Scopus (7) Google Scholar, 8Niessen LW Mohan D Akuoku JK et al.Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda.Lancet. 2018; 391: 2036-2046Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar In addition, there is increasing recognition of the late chronic consequences of major infections, exemplified by post-tuberculosis lung damage, metabolic consequences in HIV, neuropathologies from meningitis and malaria, and chronic morbidity from neglected tropical diseases such as lymphatic filariasis. These trends demand a shift towards the development and stepped-up provision of new and integrated models of care for chronic conditions, especially in low-income and middle-income settings.7Garrib A Birungi J Lesikari S et al.Integrated care for human immunodeficiency virus, diabetes and hypertension in Africa.Trans R Soc Trop Med Hyg. 2018; (published online Sept 28.)DOI:10.1093/trstmh/try098Crossref PubMed Scopus (7) Google Scholar Positive evidence for fixed-dose combinations is accumulating, along with affordable strategies to improve access to, and use of, effective medical prevention and treatment, especially in chronic conditions.4Bateman ED Reddel HK O'Byrne PM et al.As-needed budesonide-formoterol versus maintenance budesonide in mild asthma.N Engl J Med. 2018; 378: 1877-1887Crossref PubMed Scopus (187) Google Scholar, 5Bazargani YT de Boer A Leufkens HG Mantel-Teeuwisse AK Selection of essential medicines for diabetes in low and middle income countries: a survey of 32 national essential medicines lists.PLoS One. 2014; 9e106072Crossref PubMed Scopus (17) Google Scholar, 6Beasley R Fingleton J Weatherall M Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma.Thorax. 2013; 68: 119-120Crossref PubMed Scopus (7) Google Scholar, 9Lung T Jan S de Silva HA et al.Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30343-2Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 10Lin JK Moran AE Bibbins-Domingo K et al.Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling study.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30339-0Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 11Hwang TJ Keshavjee S Global financing and long-term technical assistance for multidrug-resistant tuberculosis: scaling up access to treatment.PLoS Med. 2014; 11e1001738Crossref PubMed Scopus (9) Google Scholar, 12Murray CJ Lauer JA Hutubessy RC et al.Effectiveness and costs of interventions to lower systolic blood pressure and cholesterol: a global and regional analysis on reduction of cardiovascular-disease risk.Lancet. 2003; 361: 717-725Summary Full Text Full Text PDF PubMed Scopus (440) Google Scholar, 13Gallardo CR Rigau Comas D Valderrama Rodríguez A et al.Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis.Cochrane Database Syst Rev. 2016; 5CD009913Google Scholar Fixed-dose combinations have important advantages for patients and health systems, including simpler dose schedules, decreased pill burden, reduced stockouts, and easier task sharing, training, and supervision compared with single-pill strategies, resulting in promotion of large-scale access, acceptance, and production, such as recommended by Thomas Lung and colleagues9Lung T Jan S de Silva HA et al.Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30343-2Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar and John Lin and colleagues10Lin JK Moran AE Bibbins-Domingo K et al.Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling study.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30339-0Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar in The Lancet Global Health. Lung and colleagues9Lung T Jan S de Silva HA et al.Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30343-2Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar report both health and economic benefits of a fixed-dose combination triple pill, comprising amlodipine, telmisartan, and chlorthalidone, in the treatment of high blood pressure in an economic analysis of the Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial.14Webster R Salam A de Silva HA et al.Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial.JAMA. 2018; 320: 566-579Crossref PubMed Scopus (65) Google Scholar This triple-pill strategy has been proven to improve patients' adherence to medication regimens and blood pressure control rates compared with usual care in Sri Lanka, and Lung and colleagues show that this strategy reduced health-care costs and improved outcomes in terms of life-years gained and disability prevented. Consequently, in an unusually rapid reaction, WHO, with the support of relevant societal and professional organisations, has recently added fixed-dose combinations of blood pressure lowering drugs to its Essential Medicines List, which is essential to improve the availability and affordability of these drugs. It is a shining example of international coordination and collaboration. Addition to the list enables more than 1 billion people with high blood pressure worldwide to regularly take medication that can prevent strokes and myocardial infarctions, and thereby reduce the risk of disability in middle age and premature death.15WHOFixed-dose combination antihypertensives.https://www.who.int/selection_medicines/committees/expert/22/fixed-dose_combination_antihypertensives/en/Date accessed: August 18, 2019Google Scholar Inevitably, the economic study by Lung and colleagues9Lung T Jan S de Silva HA et al.Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30343-2Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar is based on limited empirical observations as patients were followed up for only 2 years and the differences in blood pressure between the triple-pill and usual care groups showed a plateau after 6 weeks in the TRIUMPH trial. The TRIUMPH trial cannot be considered as a pure efficacy trial. In real-life settings, one can expect short-term compliance and Hawthorne effects, whereas in the long-term economic evaluation changes in long-term behaviour and compliance are important.9Lung T Jan S de Silva HA et al.Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30343-2Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar In addition, non-linearity of the risk functions, depending on absolute blood pressure levels, age, and selective survival effects might result in huge differences in outcomes between subpopulations. Lin and colleagues10Lin JK Moran AE Bibbins-Domingo K et al.Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling study.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30339-0Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar take fixed-dose combinations one step further and show the potential health effects and cost reductions of the large-scale introduction of fixed-dose combinations including aspirin, lisinopril, atenolol, and simvastatin to address multiple risk factors. Their careful and well documented model-based economic analyses attempt to assess the options for secondary cardiovascular disease risk prevention in large country populations across the world. They recommend a large-scale introduction of this polypill for secondary prevention as the study shows that among adults aged 30–84 years with established atherosclerotic cardiovascular disease, compared with current care, it would avert 40–54 major adverse cardiovascular events for every 1000 patients treated for 5 years, with an incremental cost-effectiveness ratio compared with current care on the basis of public sector prices over a lifetime analytical horizon of Int$168 (95% uncertainty interval 55 to 337) per disability-adjusted life-year averted in China, $154 (57 to 289) in India, $88 (15 to 193) in Mexico, $364 (147 to 692) in Nigeria, and $64 (cost-saving to 203) in South Africa (0·4–6·2% of the per capita gross domestic product in these countries). These estimates are three to four times higher in case of retail market prices. There is one caveat: aspirin in primary cardiovascular disease prevention was recently shown to be ineffective.16McNeil JJ Woods RL Nelson MR et al.Effect of aspirin on disability-free survival in the healthy elderly.N Engl J Med. 2018; 379: 1499-1508Crossref PubMed Scopus (189) Google Scholar Secondary prevention in polypill trials showed improvements in proxy outcomes, but not in mortality outcomes, possibly because of an insufficient sample size or follow-up duration. Primary and secondary cardiovascular disease prevention had been assessed as early as 2003, including the potential benefits of polypill combinations.8Niessen LW Mohan D Akuoku JK et al.Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda.Lancet. 2018; 391: 2036-2046Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar Other treatment combinations are already in use in the treatment of chronic conditions, including lung health,3Babar ZU Lessing C Mace C Bissell K The availability, pricing and affordability of three essential asthma medicines in 52 LMICs.Pharmacoeconomics. 2013; 31: 1063-1082Crossref PubMed Scopus (42) Google Scholar, 4Bateman ED Reddel HK O'Byrne PM et al.As-needed budesonide-formoterol versus maintenance budesonide in mild asthma.N Engl J Med. 2018; 378: 1877-1887Crossref PubMed Scopus (187) Google Scholar, 6Beasley R Fingleton J Weatherall M Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma.Thorax. 2013; 68: 119-120Crossref PubMed Scopus (7) Google Scholar diabetes,5Bazargani YT de Boer A Leufkens HG Mantel-Teeuwisse AK Selection of essential medicines for diabetes in low and middle income countries: a survey of 32 national essential medicines lists.PLoS One. 2014; 9e106072Crossref PubMed Scopus (17) Google Scholar HIV, and tuberculosis.7Garrib A Birungi J Lesikari S et al.Integrated care for human immunodeficiency virus, diabetes and hypertension in Africa.Trans R Soc Trop Med Hyg. 2018; (published online Sept 28.)DOI:10.1093/trstmh/try098Crossref PubMed Scopus (7) Google Scholar, 11Hwang TJ Keshavjee S Global financing and long-term technical assistance for multidrug-resistant tuberculosis: scaling up access to treatment.PLoS Med. 2014; 11e1001738Crossref PubMed Scopus (9) Google Scholar In lung health, there is the question of whether a simple strategy of using a combined corticosteroid–rapid-onset long-acting β2 agonist inhaler as required or, if clinically indicated, both as required, and regularly, reduces asthma exacerbations in children and adults in low-income and middle-income settings, with a possible potential role in the management of post-tuberculosis chronic lung disease.4Bateman ED Reddel HK O'Byrne PM et al.As-needed budesonide-formoterol versus maintenance budesonide in mild asthma.N Engl J Med. 2018; 378: 1877-1887Crossref PubMed Scopus (187) Google Scholar, 6Beasley R Fingleton J Weatherall M Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma.Thorax. 2013; 68: 119-120Crossref PubMed Scopus (7) Google Scholar Rigorous epidemiological and economic evaluation of fixed-dose combinations is complex: monotherapeutic strategies, in many cases, are the norm and widely accepted in health guidelines and in clinical practice. Both insufficient effectiveness information and ethical boundaries in the identification of control groups make the use of mathematical modelling unavoidable.17Bertram MY Lauer JA De Joncheere K et al.Cost-effectiveness thresholds: pros and cons.Bull World Health Organ. 2016; 94: 925-930Crossref PubMed Scopus (282) Google Scholar, 18Sanders GD Neumann PJ Basu A et al.Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine.JAMA. 2016; 316: 1093-1103Crossref PubMed Scopus (1077) Google Scholar In a state-of-the-art approach, Lin and colleagues10Lin JK Moran AE Bibbins-Domingo K et al.Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling study.Lancet Glob Health. 2019; (published online Aug 30.)http://dx.doi.org/10.1016/S2214-109X(19)30339-0Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar used estimates from the Prospective Urban Rural Epidemiology (PURE) study, including compliance, as a control. They used the proxy outcomes of a single trial in a low-income and middle-income country and the aggregated compliance data from two trials in high-income countries, calibrated against recent burden of disease estimates. They optimistically include the health effects of the four individual drugs on secondary event prevention among post-first-event patients. These combined, multiplicative, indeed proxy effects of their polypill are simulated in scenarios to estimate the potential population benefits. It is realistic to weigh the benefits against both the health-care cost based on international generic pricing versus existing local commercial pricing. However, the assumed potential cost-offsets from preventing secondary events will be low in many resource-limited settings. Hopefully, in the near future, monitoring the implementation of up-scaling efforts will teach us about the real-life effectiveness of these fixed-dose combinations. Findings from economic evaluations—cost-effectiveness estimates—often stimulate debates on what cost-effectiveness threshold is economically attractive. The WHO-CHOICE programme has modified its position substantially after the Second Panel on Cost-Effectiveness.17Bertram MY Lauer JA De Joncheere K et al.Cost-effectiveness thresholds: pros and cons.Bull World Health Organ. 2016; 94: 925-930Crossref PubMed Scopus (282) Google Scholar The Panel concluded that there is no absolute cost-effectiveness threshold and that individual countries should define their own approach.18Sanders GD Neumann PJ Basu A et al.Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine.JAMA. 2016; 316: 1093-1103Crossref PubMed Scopus (1077) Google Scholar The UK, through the threshold of £20 000–30 000 per healthy-year gained set by the UK National Institute for Health and Care Excellence, is the only country that applies an absolute standard in decision making on package formulations. The best approach globally is to respect national governmental decision making that can take into account country standards, the overall situation in the country, and the particulars of the health system.17Bertram MY Lauer JA De Joncheere K et al.Cost-effectiveness thresholds: pros and cons.Bull World Health Organ. 2016; 94: 925-930Crossref PubMed Scopus (282) Google Scholar, 18Sanders GD Neumann PJ Basu A et al.Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine.JAMA. 2016; 316: 1093-1103Crossref PubMed Scopus (1077) Google Scholar, 19Baltussen R Jansen MP Bijlmakers L Tromp N Yamin AE Norheim OF Progressive realisation of universal health coverage: what are the required processes and evidence?.BMJ Glob Health. 2017; 2e000342Crossref PubMed Scopus (14) Google Scholar, 20Baltussen R Niessen L Priority setting of health interventions: the need for multi-criteria decision analysis.Cost Eff Resour Alloc. 2006; 4: 14Crossref PubMed Scopus (388) Google Scholar However, one would like to see an earlier involvement of funding bodies, both internationally and nationally. Real-life policy making in low-income settings is complex and will increase in complexity as more options become available to deal with the health burden of chronic conditions. Although cost-effective, the overall national budget impacts, especially in the larger countries, of most new intervention packages can nevertheless be huge, as the number of people with chronic conditions is ever increasing. Assuming concurrent retail market pharmaceutical prices, these budgets might be at 10% of the per capita gross domestic product. Would ministries of health and finance or national cabinets prefer to use this money in a different way in health or otherwise? Inevitably, the ongoing equity debates in allocation of country resources have been part of national decision making for decades, especially in the case of low-income and middle-income countries. It is striking that the UN Sustainable Development Goals' leading themes are the inequalities between population subgroups, including gender, the poor, the disabled, and minorities but also the huge inequalities between countries. These equity questions have not been clearly addressed in the two studies, or in most other recent evaluations. Certainly, from now on, progressive realisation—ie, the promotion of equity in universal access and coverage—will be higher on the agenda, given proven effectiveness and efficiency of new interventions and strategies.1UNMoving together to make the world a healthier place.https://www.un.org/pga/73/event/universal-health-coverage/Date accessed: August 15, 2019Google Scholar, 2UN Statistics DivisionThe Sustanability Development Goals report.https://unstats.un.org/sdgs/report/2019/The-Sustainable-Development-Goals-Report-2019.pdfDate: 2019Date accessed: August 18, 2019Google Scholar, 19Baltussen R Jansen MP Bijlmakers L Tromp N Yamin AE Norheim OF Progressive realisation of universal health coverage: what are the required processes and evidence?.BMJ Glob Health. 2017; 2e000342Crossref PubMed Scopus (14) Google Scholar, 20Baltussen R Niessen L Priority setting of health interventions: the need for multi-criteria decision analysis.Cost Eff Resour Alloc. 2006; 4: 14Crossref PubMed Scopus (388) Google Scholar, 21The LancetPrioritising disability in universal health coverage.Lancet. 2019; 394: 187Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar To promote acceptance, funding, and access, existing recommendations in relation to the upcoming high-level UN meeting should be kept in mind: they focus on political leadership beyond health, to exclude no one, to regulate and legislate, internationally and nationally the upcoming universal health coverage efforts, while upholding quality of care.1UNMoving together to make the world a healthier place.https://www.un.org/pga/73/event/universal-health-coverage/Date accessed: August 15, 2019Google Scholar Universal coverage of prevention and treatment of chronic conditions will have to be a substantial part of this international collaborative process, to reduce inequalities in financing of, access to, and use of treatments, between countries and within countries.19Baltussen R Jansen MP Bijlmakers L Tromp N Yamin AE Norheim OF Progressive realisation of universal health coverage: what are the required processes and evidence?.BMJ Glob Health. 2017; 2e000342Crossref PubMed Scopus (14) Google Scholar, 20Baltussen R Niessen L Priority setting of health interventions: the need for multi-criteria decision analysis.Cost Eff Resour Alloc. 2006; 4: 14Crossref PubMed Scopus (388) Google Scholar, 21The LancetPrioritising disability in universal health coverage.Lancet. 2019; 394: 187Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar We declare no competing interests. We are supported by the UK National Institute for Health Research (NIHR) Foundation project grant 16/136/35 for NIHR Global Health Research Unit ‘IMPALA’ (LWN, SBS) and grant 16/137/87 on HIV- NCDs (LWN), using Official Development Assistance funding. The views expressed are not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health. Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trialCompared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease. Full-Text PDF Open AccessCost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling studyThe polypill is projected to be cost-effective compared with current care for secondary prevention of atherosclerotic cardiovascular disease in China, India, Mexico, Nigeria, and South Africa, particularly if it is made available at public-sector pricing. However, achieving meaningful improvements in cardiovascular health will require simultaneous investments in health infrastructure to increase the uptake of the polypill among patients with established atherosclerotic cardiovascular disease. Full-Text PDF Open Access