Comment
Universal health coverage and chronic conditions
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.1,2 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.3–8
In addition, there is increasing recognition of the late
chronic consequences of major infections, exemplified
by post-tuberculosis lung damage, metabolic conse­
quences 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.7 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.4–6,9–13 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 colleagues9 and John Lin and colleagues10 in
The Lancet Global Health.
Lung and colleagues9 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.14 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
www.thelancet.com/lancetgh Vol 7 October 2019 e1290
organisations, has recently added fixed-dose Published Online
August 30, 2019
combinations of blood pressure lowering drugs to its http://dx.doi.org/10.1016/
Essential Medicines List, which is essential to improve S2214-109X(19)30366-3
the availability and affordability of these drugs. It is See Articles page e1346 and
e1359
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.15
Inevitably, the economic study by Lung and colleagues9
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.9 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 colleagues10 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
 Comment
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.16 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.8
Other treatment combinations are already in use in
the treatment of chronic conditions, including lung
health,3,4,6 diabetes,5 HIV, and tuberculosis.7,11 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.4,6
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.17,18
In a state-of-the-art approach, Lin and colleagues10
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
e1291 www.thelancet.com/lancetgh Vol 7 October 2019
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.17 The Panel concluded that there is no
absolute cost-effectiveness threshold and that individual
countries should define their own approach.18 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.17–20
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.1,2,19–21
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.1 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.19–21
*Louis W Niessen, S Bertel Squire
Faculty of International Public Health and Clinical Sciences,
Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK (LWN,
SBS); Department of International Health, Johns Hopkins
Bloomberg School of Public Health, Baltimore, MD, USA (LWN)
louis.niessen@lstmed.ac.uk
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.
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open
Access article under the CC BY 4.0 license.
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