www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X 1
In 1980, the World Development Report1 emphasised
that developing countries are home to 78% of the global
population, but to 86% of the world’s children.
The proportion of children in developing countries is
expected to increase to more than 90% by 2030.
Although infectious diseases are much more prevalent
than cancer in developing countries, more deaths are
caused by cancer worldwide than by HIV infection,
tuberculosis, and malaria combined; cancer incidence is
higher in developing countries (147 000 cases per year)
than in developed countries, and is growing because the
populations in these countries are younger and
expanding.2 As a result, up to 2% of all cancers
in developing countries arise in children, whereas
in Europe and North America, childhood cancers
constitute less than 0·5% of total incident cases.
The essential policy issues framing the global care
agenda for children with cancer are not only those
intrinsic to paediatric oncology, but—particularly in
developing countries—are also a product of a country’s
stage of economic development, its ensuing patterns of
disease, and the sociopolitical constructs that aff ect
health (fi gure 1).3
According to estimates by the International Agency for
Research on Cancer for 2008, almost 100 000 deaths
before the age of 15 result from cancer every year, and
more than 90% of these deaths occur in low-middle
income countries (fi gure
socioeconomic development, the proportion of deaths
from cancer is likely to increase in developing countries,
especially in young people. Mortality is high in developing
countries—80% of young cancer patients in Africa die,
including in countries with more developed health
systems such as South Africa. Available data probably
underestimate the burden of childhood cancer in
2).2 With continued
developing countries because the patterns of occurrence
suggest that many patients die from undiagnosed cancer.
Nowadays, about 80% of children with cancer in high-
income countries survive.4 However, in resource-limited
settings, many cases of cancer are detected too late for
eff ective treatment, and
comorbidities (especially malnutrition), aff ordability,
and restricted access to treatment and care.5 The burden
and range of childhood cancers varies substantially
between countries. Global policies to address the care,
education, and study of children with cancer and their
families need to deal with both commonalities—eg, the
eff ect of legislation on childhood cancer research and
development—and the specifi c contexts of where these
children live. Because socioeconomic, demographic, and
are compounded by
Improving cancer care for children and young people 4
New policies to address the global burden of childhood cancers
Richard Sullivan, Jerzy R Kowalczyk, Bharat Agarwal, Ruth Ladenstein, Edel Fitzgerald, Ronald Barr, Eva Steliarova-Foucher, Ian Magrath,
Scott C Howard, Mariana Kruger, Maria Grazia Valsecchi, Andrea Biondi, Paul Grundy, Malcolm A Smith, Peter Adamson, Gilles Vassal,
Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of
15 years, more than 90% of them in resource-limited countries. Here, we review the key policy issues for the delivery
of better care, research, and education of professionals and patients. We present a key list of time-limited proposals
focusing on change to health systems and research and development. These include sector and system reforms to
make care aff ordable to all, policies to promote growth of civil society around both cancer and Millennium
Development Goals, major improvements to public health services (particularly the introduction of national cancer
plans), improved career development, and increased remuneration of specialist health-care workers and government
support for childhood cancer registries. Research and development proposals focus on sustainable funding, the
establishment of more research networks, and clinical research specifi cally targeted at the needs of low-income and
middle-income countries. Finally, we present proposals to address the need for clinical trial innovation, the complex
dichotomy of regulations, and the threats to the availability of data for childhood cancers.
February 20, 2013
This is the fourth in a Series of
four papers about improving
cancer care for children and
Institute of Cancer Policy,
King’s Health Partners
Integrated Cancer Centre,
(Prof R Sullivan MD);
Department of Paediatric
Haematology, Oncology, and
University, Lublin, Poland
(Prof J R Kowalczyk MD);
Department of Paediatric
Haematology and Oncology,
B J Wadia Hospital for Children,
Mumbai, India (B Agarwal MD);
Children’s Cancer Research
Institute, St Anna Children’s
Hospital, Vienna, Austria
(Prof R Ladenstein MD);
European Cancer Organisation,
(E Fitzgerald PhD); Department
Figure 1: Policy issues surround the struggle to improve childhood cancer survival
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X
political circumstances vary widely in developing
countries, eff ective cancer treatment for children will
need strategies that are adapted to individual countries
with limited resources. The policy myth that developing
countries cannot aff ord to treat children with cancer
needs to be debunked. High cure rates in children result
in many potential years of life saved, and for some
childhood cancers, such as Burkitt’s lymphoma and
Wilms’ tumour, aff ordable treatments can be highly
eff ective when given appropriately.6 Formal economic
evaluation, by use of quality-adjusted life-years, has
shown that treatment of cancer in children is a very cost-
eff ective investment,7,8 particularly for cancers such as
Burkitt’s lymphoma and acute lymphoblastic leukaemia,
which are curable in children.
The quantity and quality of statistics describing burden
of disease in developing regions vary. In Africa, only
three countries—Mauritius, South Africa, and Egypt—
provide cancer mortality statistics to the WHO mortality
database, and only about 1% of the African population is
covered by reliable population-based cancer registries
providing data on cancer incidence (fi gure 3).9 The
population data—which are needed to produce incidence
and mortality rates—are not available or are insuffi cient;
therefore, the statistics are based on little real data.
Existing population-based cancer registries are the
forerunners of the cancer control plan, and should
therefore receive wide-ranging support to continue
providing unique and indispensable information about
cancer burden.10 Despite resource limitations, several
middle-income countries—eg, Argentina, South Africa,
and Iran—have implemented national population-based
cancer registration for children, with support from non-
governmental organisations in some cases.11
In high-income countries in the past few decades, the
most substantial gains in outcomes have been in
childhood cancers. 5-year survival has increased from
less than 30% in the 1960s to about 80% in the 2000s for
all childhood cancers combined.12,13 The most important
reason for this achievement is the integration of care and
research in paediatric oncology; however, serious policy
issues exist—eg, the future sustainability of research and
development, integrated care networks, and the eff ect of
regulations. We look at the issues and solutions from the
other papers in this Series14–16 and propose solutions for
all children with cancer for the next decade, irrespective
of where in the world they live.
High-income countries: changing the policy
Outcomes in children in high-income countries have
substantially improved, but have varied with cancer type
and geography.14 Despite an overall improvement in
childhood 5-year survival,12,13 several solid cancers are still
refractory to treatment. As discussed by Vassal and
colleagues,16 this lack of response is partly attributable to a
lag in the scientifi c understanding of these types of cancer,
but also to the translation of adult research and
development into the paediatric setting. Importantly for
policy makers at the national and supranational level,
Pritchard-Jones and colleagues14 state that improvements
in effi cacy of present regimens and treatment approaches
are reaching their limit, and, despite substantial
improvements in outcomes, we are a long way from
curing all children with cancer. Furthermore, even for the
children saved by present approaches, long-term toxicity
and the associated eff ects on future health remain
important.17 The risks include continuing excess mortality,
second primary neoplasms, neurocognitive defects,
cardiovascular disease, other organ dysfunction, and the
psychosocial eff ects of disease and its treatment on the
patient and their family.18 The policy environment for
adults who survived childhood cancer needs to be
reviewed, irrespective of any health consequences.
Survivors aged 30–50 years have much the same general
indicators of economic achievement and insurability as do
people in the same age group who did not have cancer as
children.19 But despite this, survivors in this age group are
denied entry into the military and can have applications
for life insurance rejected. Survivors aged 20–29 years are
worse off than those who have not had cancer in several
areas including educational achievement, employment,
workplace and social relationships, and the ability to
obtain health and life insurance.
Although we have the knowledge and methods to deliver
excellent outcomes in many childhood cancers, the
of Pathology and Department
of Medicine at McMaster
University, Hamilton, ON,
Canada (Prof R Barr MD);
for Research on Cancer,
(E Steliarova-Foucher PhD);
International Network for
Cancer Treatment and
Research, Brussels, Belgium
(Prof I Magrath MD);
Department of Oncology,
St Jude Children’s Research
Hospital, Memphis, TN, USA
(S C Howard MD); Department
of Paediatrics and Child Health,
Faculty of Medicine and Health
University, Tygerberg, Cape
Town, South Africa
(Prof M Kruger MD); Center of
Biostatistics for Clinical
Epidemiology, University of
Milan-Bicocca, Monza, Italy
(M G Valsecchi MD);
Department of Paediatrics,
University of Milano-Bicocca,
Monza, Italy (Prof A Biondi MD);
Alberta Health Services,
Edmonton, AB, Canada
(P Grundy MD); National
Institutes of Health, Rockville,
MD, USA (M A Smith MD);
Division of Clinical
Figure 2: Cancer deaths as a percentage of total deaths, 2008
Actual numbers of cancer deaths are shown next to the bars.2 WHO, Health Statistics and Informatics Department,
World Health Organization, Geneva, Switzerland, 2011. http://www.who.int/evidence/bod (accessed Nov 21, 2012).
Cancer deaths (%)
7 771 478
7 512 864
3 663 069
3 507 850
1 155 957
1 119 741
2 469 746
2 452 030
≥30 years of age
15–29 years of age
0–14 years of age
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X 3
Therapeutics, The Children’s
Hospital of Philadelphia,
Philadelphia, PA, USA
(P Adamson MD); Institut
France (Prof G Vassal MD); and
Institute of Child Health,
University College London,
(Prof K Pritchard-Jones MD)
Prof Richard Sullivan, Institute of
Cancer Policy, King’s Health
Partners Integrated Cancer
Centre, Guy’s Hospital Campus,
SE1 9RT London, UK
diff erences in outcomes between more and less affl uent
populations—irrespective of whether these are in high-
income or low-income countries—is concerning. In
developing countries, one of the strongest determinants of
childhood mortality is the socioeconomic class of parents
(fi gure 4).20 In high-income settings, diff erences in
geographical outcome fell between 2005 and 2009;
however, childhood cancer mortality is more than 20%
higher in central and eastern Europe than in the rest of
Europe (fi gure 5).20 To close this gap, the underlying
reasons for the divergence need to be understood, and
social and health policies need to be introduced. Attempts
to help with transnational clinical research in Europe have
unintentionally had negative consequences.22 Paediatric
oncology groups from several central and eastern
European counties were involved in international clinical
trials before their countries joined the European Union
(EU); almost all of the front-line treatments involved the
off -label use of long established medicines that were out of
patent. This situation was generally accepted by regulatory
authorities, and the trials were seen as obligatory standards
for the treatment of childhood cancer. However,
implementation of European directives led to the
overinterpretation of some regulatory requirements,
without any funding to support the infrastructure changes
necessary for compliance. Both research-active care
networks and the viability of the care centres were adversely
aff ected. For example, Polish paediatric oncology centres
are not currently able to open any new academic clinical
trials because the universities do not have the resources to
meet the responsibilities assigned to the sponsor role by
the Polish Government.23 Very little government or
philanthropic funding is available to support cancer care in
these countries.24 From a policy perspective, the crucial
work is to attempt to revise European clinical trials
legislation and provide advocacy, such as the European
Society of Paediatric Oncology’s promotion of national
support for childhood cancer research.
Although comparable statistics are available in high-
income countries, funding cuts and unjustifi ed
requirements on data confi dentiality pose a challenge to
established cancer registries. National population-based
cancer registries should be advocated for childhood
cancers because of their rare occurrence, centralised
treatment, internal migration, data quality, and cost
considerations, as recommended by EUROCOURSE
ERA-Net. To improve interpretation of follow-up and
outcome data, clinical trial groups or consortia can
enhance the quality of their data and enlarge their database
with clinically relevant information. Additionally, precise
statistics can help to identify gaps and outline directions
for improvement—further reduction of mortality,
extension of long-term survival, and limitation of
treatment-related late side-eff ects.25 Registries are not just
important in high-income countries, and policy makers
can learn from good models being implemented in
emerging economies such as South Africa.26
Why have the cancer communities in high-income
countries been so successful in improving outcomes in
the past 30 years? One of the major lessons learnt has
been for the care and research communities to organise
themselves to deliver a continuously innovating system of
care, with research fully integrated into clinical pathways.
Innovation in the organisation of care in high-income
countries has enabled the localisation and eff ective
networking of appropriate expertise, data collection, and
research. Clinical trials have also had an important role in
the improvement of outcomes; the accrual rate is an order
of magnitude greater for children than for adults in high-
income countries, and enrolment on available clinical
trials at fi rst diagnosis has become the standard of care—
an important point often not acknowledged by policy
makers. The eff ective management of children with
cancer needs long-term commitment from both health-
care professionals and federal authorities to support
research and care networks. The gains in outcomes
should be seen in the context of other major issues, and
drawbacks that arise as health-care and political systems
change. In terms of policy, high-income countries still
need continuous vigilance and development.
Low-income countries: improving outcomes
The burden and eff ect of childhood cancers in developing
countries is complex; level of income, social indicators
(eg, general health and education), vulnerability and risk,
and sociopolitical access all play a part.27 Poverty aff ects
health and mortality at all ages, but particularly children,
including those children from less affl uent backgrounds
in high-income countries.28 As well as the direct eff ect of
poverty, low-income countries have poor health-care
provision, which means that few special cancer centres
Figure 3: Incidence and mortality rates of childhood cancer, and percentage of population covered by cancer
Percentage fi gures above the bars are the percentage of the population covered by cancer registries. Reproduced
with permission from Eva Steliorova Foucher.
EuropeLatin America AfricaNorth America OceaniaAsia
Number per 100 000
For the EUROCOURSE ERA-Net
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are available, and if they are, they are likely to be a long
and expensive journey away. 80% of people in Africa
have no access to radiotherapy, cancer surgery, or the
infrastructure needed for the basic delivery of cancer
care.29 Suffi cient numbers of health-care workers and
adequate levels of fi nancial capital to bring health care to
all do not exist. Such substantial intrinsic hurdles
seriously compromise the development of services for
children with cancer. From a policy perspective, catalytic
programmes are needed to overcome this inertia.30
Twinning is extremely important; the term encompasses
the engagement of centres in high-income countries
with developing countries, but also more regional
programmes such as the links between Northern and
South Africa with sub-Saharan Africa.31
Developing countries can be optimistic for the future.
Social and health conditions are improving in many parts
of the world—eg, growth in per-person private
consumption in developing countries increased from
1·4% per year between 1980 and 1990, to 2·4% between
1990 and 1999, and the percentage of people living in
extreme poverty (ie, less than US$1 a day) fell from 28% in
1987 to 23% in 1998, and 19% in 2009. Policies to increase
social capital—ie, the development of social relations and
networks that produce strong societal bonding, mutuality,
and solidarity—around children with cancer will play a
major part in the delivery of better access and services.32
While patients’ organisations and advocacy movements
are a young social phenomenon in many developing
countries, the drive to create them has been led by the
childhood cancer community in many parts of the world.
Wilkinson33 stated that social capital is essential for the
enhancement of equitable service performance through
the engagement of civil society to advocate for services
and hold providers to account. The eff ect of poor social
capital on outcomes in children with cancer is pronounced.
In one study of outcomes in children with acute
lymphoblastic leukaemia in Indonesia, 47% of parents
from deprived areas refused or abandoned treatment
compared with 2% from affl uent areas.34 The same study
suggested that strong social hierarchical structures
hindered communication with doctors, and resulted in
insuffi cient parental understanding of the need to
Infant mortality rates fell from 107 to 59 per 1000
livebirths between 1970 and 1999, and adult literacy rose
from 53% in 1970 to 74% in 1998.35 These changes are
important because a lack of young people who are
Figure 4: Mortality in children younger than 5 years per 1000 livebirths by wealth quintile, in six developing countries
Data are from demographic and Health Surveys survey data from 1996–2004.
Mortality in children younger than 5 years (per 1000 livebirths)
VietnamBrazil Cameroon Burkina FasoIndiaMali
For the Institute for Health
Metrics and Evaluation
Demographic and Health
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qualifi ed to attend university limits the capacity for
training health-care workers. Cancer care depends on a
range of professions, including engineers, pharma-
cologists, and many specialists such as ophthalmologists,
radiologists, and pathologists, in addition to the oncology
community. The introduction of education and social
capital policies in developing countries, and the
development of dedicated units for treating children with
cancer, will be essential for the delivery of adequate
childhood cancer services.36
The most important determinant of outcome for a child
with cancer is where he or she is born. In south Asia, four
out of ten households (more than 500 million people) are
in poverty, and infant and child mortality varies widely
between diff erent regions. In our health lifecycle,
childhood is one of the most vulnerable periods with
respect to disease and ill health because of biological and
socioeconomic immaturity; therefore, children suff er the
consequences of poverty more than adults.37 Parental
income is an important determinant of child cancer
inequalities across countries, but other determinants—
eg, education, the political situation, and environ ment—
are also important.38 Average country income has a strong
indirect eff ect on maternal education, which has a major
infl uence on child health.39 Maternal education is closely
related to a woman’s control over household issues,
including awareness of health issues. Additionally,
accessibility to health services is very important; countries
that have achieved good health at low cost also had health
systems that were free at the point of delivery and easy to
access. Unsurprisingly, high maternal mortality rates are
associated with regions of high childhood cancer
mortality. Diff erences between regions in female access
to education also aff ect the ability of countries to deliver
improved childhood cancer services—eg, India has a
16·6% diff erence between the school enrolment of girls
and boys aged 6–14 years. In Niger, the enrolment rate
of boys is 41% higher than that of girls. The development
of health policy is as important as are cancer-specifi c
initiatives in developing countries.
New policies to support research into childhood
A new paradigm for drug development
Drug development for cancer has progressed from
cytotoxic regimens to molecularly targeted agents.40
Molecular dissection, targeted agents, and biomarker
codevelopment have shaped and driven adult oncology,
and are now being applied to some childhood cancers
previously defi ned in anatomical terms—eg biomarkers
are available for medulloblastoma and neuroblastoma.41
However, increased understanding of the complex
biology of certain cancers, and their subsequent
molecular characterisation, has not been easily or quickly
translated into improved outcomes. This shortfall might
be an issue of scientifi c progress in the elucidation of
complex biological pathways in childhood cancers, or
something more fundamental—eg, higher-resolution
pictures of cancer might not necessarily translate into
improved outcomes. Likewise, Vassal and colleagues16
point out that only some of the identifi ed targets might
be treatable with present technologies. Furthermore, the
economic ability to develop drugs for rare targets is a
serious policy issue. Although molecular characterisation
of adult malignant disease has paved the way for novel
drug development, many of the paediatric targets diff er
Figure 5: Relation between annual governmental health-care expenditure and childhood cancer survival, 2008
5-year survival for all countries in red (from Bangladesh to Venezuela) were not measured, but derived from a survey of health professionals. Reproduced with
permission from reference 21.
5-year survival (%)
10 100 1000 10 0000
Annual government spending on health care per person (US$)
r2=0·882, p=0·0001r2=0·469, p=0·134r2=0·108, p=0·273
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from those in adults. Big challenges remain in the
translation of the science of childhood cancers into new
drugs, and specifi c programmes and funds are needed to
drive this fundamental research.42 Moreover, the short-
term and long-term toxicity profi les of these new agents
are very unpredictable.
Importance of clinical trials
Clinical trials have had, and will continue to have, an
essential role in the development of novel drugs for
children with cancer. The high rates of recruitment to
clinical trials contributed to one of paediatric oncology’s
greatest achievements—a substanital improvement in
survival. However, as the biology of childhood cancers
becomes better understood,43 and more targeted drugs
are developed, the paediatric research community needs
to embrace novel trial designs and biomarker
codevelopment strategies.44 Other crucial areas for
evolution are the harmonisation of response defi nitions,
and the use of response as a continuous variable.
Importantly, for development of cooperative clinical
trials between North
harmonisation of procedures
development is urgently needed.45 Furthermore, the
codevelopment of biomarkers found from biospecimen
collection and the addition of various novel imaging
methods in several trial settings need to catch up with
the adult fi eld. Beyond the issue of trial design
development, the division between clinical trial
outcomes, overall service outcomes, and service
improvement processes is a problem. Paediatric
oncology research progressed quickly during the 1980s
and 1990s because the boundary between research and
service improvement was less obvious than it is now. As
clinical trials develop and become more focused because
of the molecular characterisation of cancers, inclusion
criteria will become more rigorous and, therefore, will
exclude many patients. To ensure outcome is not
compromised, patients who do not enter trials should
undergo the same rigor of investigation and staging of
disease as do patients in clinical trials. Countries should
ensure that quality outcomes are monitored both
nationally and for each treating centre.
Treatment of children with cancer in the foreseeable
future will continue to rely on regimens using
chemotherapy and radiotherapy,46 both of which have
serious immediate and long-term issues of toxicity.47
Academic programmes and trial investigators need to
better prospectively explore cohorts of survivors, and to
propose adapted care for adults with long-term eff ects of
their childhood cancer treatment. This approach will
include more research into mitigation of the eff ects of
toxicity from present regimens and novel targeted
agents48 and guaranteed long-term follow-up of survivors.
This latter point is particularly important as current
pharmacovigilance requirements provide little mandated
follow-up data for new medicines.
America and Europe,
Collaboration and funding
In view of the increased biological, organisational, and
regulatory complexity, and the diversity of research and
development in childhood cancers, what new models
are needed? Vassal and colleagues remind us that
“Time is an issue. Speed up new drug development for
our children”.16 Therefore, new models of partnership
and collaboration are as much about delivering new
solutions quickly as they are about innovation. In high-
income countries, the paediatric research and
development community have long had well organised
collaborations between patients, parents, clinicians,
and scientists.49 However, the interface with the adult
drug development community and the pharmaceutical
industry still has major gaps.
The continuation and advancement of research into
children with cancer depends on long-term, sustainable
funding; however, evidence suggests that paediatric
research and development is reliant on short-term,
unsustainable funding (fi gure 6). Despite new initiatives,
this short-termism is a major concern. The US National
Cancer Institute and other parts of the National
Institutes of Health have dominant roles in North
America, and fund almost half of all paediatric oncology
research in the USA.50 In Sweden, charities and endowed
foundations fund more than 40% of research. Other
nationally prominent European funders include the
Associazione Italiana per la Ricerca sul Cancro in Italy,
Deutche Krebshilfe in Germany, the Netherlands Cancer
Society, and Cancer Research UK. The European
Commission funds only 7% of childhood cancer
research. The support of paediatric oncology research by
the EU is a positive step, but it is inadequate for the scale
of the problem. Furthermore, at the national level,
funding is too low or too unstable, with much activity
reliant on short-term funding. National and international
funding needs to be more sustainable and coherent.
The role of the pharmaceutical industry
What is the best way to identify eff ective treatments for
childhood cancers? In view of the complex and
heterogeneous nature of these cancers, the trend in the
past few years for industry to drive the development of
clinical research plans contrasts with the need for broad
research and development partnerships that can deal
with complex biology
Companies are developing research plans to meet
regulatory obligations related to the drugs that they are
developing for adult cancers. This trend takes the
primary responsibility for research direction away from
the larger paediatric oncology community, and also
tends towards the fragmentation of childhood cancer
clinical research activities—as opposed to the
cooperative, unifi ed clinical research activities that are
needed in view of the small numbers of children with
specifi c cancer types. Thus, the long-term eff ects of this
trend raise serious concerns.
and drug development.
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X 7
Re gulation aff ecting research and development in
childhood cancers has had both adverse and benefi cial
consequences. For example, in Europe, the Clinical Trials
Directive has had devastating eff ects on several publicly
funded clinical trials, particularly those focused on
childhood cancers. However, these international clinical
trials have delivered, and will continue to, deliver excellence
in care and new treatment strategies.51 The Clinical Trials
Directive has almost quadrupled costs and led to
substantial delays and even the discontinuation of trials.52
Additionally, data protection legislation (the 1995 Data
Protection Directive in Europe and the Health Insurance
Portability and Accountability Act in North America) has
negatively aff ected the ability of the paediatric research
community to share data internationally, and hindered the
activity of essential registries. In Europe at least, policy
makers seem to fi nd it diffi cult to create legislation that
promotes, rather than inhibits, life-saving research.
A planned revision to the European Data Protection
Directive is causing major concerns among cancer regis-
tries and researchers that this work will be discontinued.53
Another regulation issue was the attempt to improve
pipelines of novel compounds by regulatory mechan-
isms to drive crossover of adult new molecular entities
to the paediatric setting. In 1997, the USA, and in 2007,
the EU, introduced regulations for improved drugs for
children with cancer. In the USA, two pieces of
legislation, the Best Pharmaceuticals for Children Act
and the Pediatric Research Equity Act cover the need for
paediatric information for approved drugs. These
regulations have substantially aff ected drug develop-
ment for children with cancer, and other childhood
diseases.54 All pharmaceutical companies must now
consider paediatric oncology in their development
programmes. However, too many companies view
childhood oncology as a regulatory requirement to
comply with, rather than having a biology-based research
and development approach that integrates into the
paediatric setting.55 Furthermore, plans for drugs to
meet regulatory requirements in children are inherently
drug-focused rather than disease-focused; as a result, the
clinical trials proposed for a particular drug might be of
low clinical relevance or the eligible paediatric patients
might be extremely rare. Clinical cancer research should
maintain disease-focused prioritisation of clinical
research led by the paediatric oncology expert community
rather than drug-focused
pharmaceutical companies and regulatory authorities.
In low-income and middle-income countries, several
types of research are needed for progress. Because local
conditions change as new infrastructure and personnel
become available, the adaptation of treatment regimens
to local conditions is a continuous project. Therefore, a
system of continuous quality improvement should
become habitual in developing countries, so that
clinicians can cure as many children as possible with
existing resources, while simultaneously improving
knowledge and infrastructure to increase future cure
rates. This model is much like the one used in
high-income countries, where enrolment in a clinical
trial is deemed standard care, but diff ers in that each
centre—or region, if conditions are similar across the
region—must undertake its own implementation
research to identify gaps and areas for improvement.
For example, the Central American Paediatric
Haematology-Oncology Association, which comprises
eight centres in seven countries, uses uniform protocols
prioritisation led by
Figure 6: Mean percentage support for paediatric oncology research from various funding sectors in ten selected countries, 1997–2000 and 2005–2008
Graphs show combined totals for papers published in the two time periods. Percentages add to more than 100% because of multiple funders on some papers.
Reproduced with permission from Kathy Pritchard-Jones and colleagues.50
Proportion of papers (%)
8040 1200 100 6014020160 180
National government %
National private non-profit %Industry % International %Other %None %
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X
that have been adapted to the local setting, and carefully
monitors outcomes. These outcomes include death
from treatment toxicity and abandonment of treatment,
which are the two most common causes of treatment
failure for children with cancer.55 Twinning programmes
for individual centres, and regional networks of similar
Proposal Comments Diffi cultyWhen
Health systems and health policy
Diff erent outcomes
between children from
affl uent and deprived
Insuffi cient aff ordable
cancer care for most
children in developing
Research into the inequalities in outcomes of childhood cancers and
the development of new policies.
New health-sector reforms that target the health of poor people,
including improvements in tax to fi nance systems, reduction in cost
of services to poor people and social insurance models, and policies
that deliver services with equity and that have built in monitoring
and evaluation targets.
Develop a national childhood cancer plan with designated hospitals
certifi ed to provide care, rapid referral systems, and access to care
for the entire population.
Promote the growth of civil society in low-income countries to
support the fi nancial situation of existing childhood cancer
providers, with the International Confederation of Childhood Cancer
Patient Organisation to support and develop national organisations.
Although many emerging economies are attempting to reform their
systems, most are inequitable and have major structural defi cits. The
delivery of aff ordable care for children with cancer is associated with
overall health-care reform. However, model initiatives can and
should be developed to act as leaders both within and outside of the
Insuffi cient civil society
and advocacy to deliver
relevant to child health
The separation between infectious and non-communicable diseases
is artifi cial, and is counterproductive in public policy terms. The
international childhood-cancer advocacy movement needs to deliver
its agenda by supporting broader child health goals and helping the
childhood cancer community to advocate for the Millenium
In many countries, the basic improvement in cancer services is a
major step in delivering better childhood cancer care. Generally,
global public health initiatives drive better outcomes. Many
countries—particularly emerging economies in Latin America—have
tried and tested public health models. In Europe for example, the
European Society of Paediatric Oncology has developed European
Standards of Care for Children with Cancer,57 but these now need
High-quality epidemiological data for health-care system planning
for childhood cancers is crucial and the knowledge already exists.
However, many lower-middle-income and low-income countries will
need substantial technical and fi nancial assistance from high-income
sources to address this issue, including initiatives from major
Health-care workers in countries of low and middle income are
poorly remunerated such that they often have to rely on additional
(non-specialist) activities or move overseas.
Insuffi cient public
health systems in
Improvements in policies that help a variety of patients with acute
and chronic illnesses. For example: societal health literacy;
community and primary care; primary, secondary, and tertiary
infrastructure and personnel training; laboratory services
(particularly microbiology); infection control programmes; blood
banking; diagnostic imaging; and paediatric surgery.
Improvements in services specifi c to cancer care. For example:
pathology, chemotherapy, and radiation treatment.
Government mandated and supported programme to create
registries. Policy makers should support institutional registries
through twinning activities—eg, the Paediatric Oncology Network
Database initiative with St Jude Children’s Research Hospital,
Memphis, TN, USA—as a fi rst step to improvement in national
Specialisation of multidisciplinary health-care professionals needed
to treat cancer in children and adolescents should be recognised and
appropriately remunerated alongside career development.
Insuffi cient childhood
cancer registries in
Poor remuneration of
in the public sector
Research and development
Insuffi cient sustainable
funding mechanisms in
Government and philanthropic funders to create long-term core
infrastructure research and development funds. Increased strategic
planning between national and international funders of research
and development. Dedicated low-income and middle-income
research and development funding streams.
Although funding levels have been good in high-income countries,
the increasing trend to short-term funding works against long-term
programmes. Conversely, in low-income and middle-income
countries, levels of research and development funding are too low
Policy makers should provide government-based economic models—
eg, the US National Cancer Institute-funded Pediatric Preclinical
Testing Program—to support key steps for the development of
childhood medicines against ultra-rare targets and other novel
targets. In countries where federal engagement is suboptimum,
strategies that give advocacy groups public-relations materials to
lobby for specifi c solutions can be very eff ective. At the national and
international level—eg, FP7 European Network for Cancer Research
in Children and Adolescents—policy is urgently needed to create
sustainable funding streams to support the international networks.
Examples such as PanCare in Europe exist, but need to be substantial. High
Slow progress in
reduction of long-term
toxicity of treatments
Create and fund national and international collaborative
programmes in this area.complexity
Create more discipline-specifi c networks (eg, pathology, surgery,
and oncology), and disease-specifi c networks—eg, Burkitt’s
lymphoma (International Network for Cancer Treatment and
Research), Wilms’ tumour, neuroblastoma (Global Neuroblastoma
Both Europe and North America have a history of successful and
sustainable networks. Such a model can and should be expanded
into other areas and worldwide.
(Continues on next page)
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centres, provide the forum for international mentoring,
development of regional expertise, and generation of
generalisable knowledge that will help others who treat
children with cancer.21 The support of twinning
programmes and regional networks—and holding them
accountable for measurable results—could transform
cancer care, provide the platform to integrate new drugs
and targeted treatments on a global scale in the
intermediate term, and lead to excellent cure rates for
all children everywhere in the long term.
The experiences and needs of children with cancer and
their families in all settings, whether a high-income or a
developing country, need to be better understood.56
Policy development needs evidence and experience. The
table shows the policies proposed here and in the other
three papers14–16 in this Series to focus our eff orts to
address the global needs of children with cancer. We
need a broad and transdisciplinary approach to these
issues that brings in expertise from outside the
ProposalComments Diffi cultyWhen
(Continued from previous page)
specifi cally addressing
cancer care needs in
Innovation in clinical
Should include, but not be limited to, the development of clinical
research and development protocols that study adapted treatment
regimens, adapted supportive care strategies, abandonment
prevention strategies, cost-eff ectiveness of alternative strategies for
diagnosis, staging, risk stratifi cation, treatment, and follow-up.
The ability to develop and carry out more clinical studies in low-
income and middle-income countries is related to the funding
available to train and develop research personnel.
Research and regulatory communities should develop a range of
policies to improve harmonisation of methods of clinical trial
procedures, including a biospecimen policy and the application of
novel designs and statistical methods.
Despite regulatory divergence between Europe and North America,
major steps have already been taken to bring protocols together, and
novel statistical methods are now available for use in the paediatric
setting. Eff orts are already underway in Canada—eg, the eff orts of
the major research funders the Canadian Cancer Research Alliance to
urge the government body, Health Canada, to interpret the
regulatory laws in a more practical and less onerous way to reduce
the expense and time to carry out trials
The pharmaceutical industry should positively engage with the
paediatric research and development networks to create a new
collaborative model that brings funding, and new molecules and
biomarkers, into the existing clinical trial networks.
for research and
Pan-community models of collaboration (parents, academia,
industry, and regulators) should commit to medium-term and long-
term partnerships to deliver the next generation of innovations.
Harmonisation between procedures and processes between EU
groups (eg, ENCCA) and North America (COG) to encourage
collaboration and speed up the development and delivery of
advancements in treatment. Incorporation of regional networks of
centres in low-income and middle-income countries to provide
access to up-to-date treatments and to greatly increase the number
of patients able to participate in clinical research and provide
samples for translational research.
Legislatively mandated programme to create or sustain
population-based cancer registries, ideally with national coverage for
childhood populations. To avoid bias, should not need informed
consent or one-way encryption of the identifying data for
population-based cancer registration. Relieve constraints on
publication of grouped cancer data to encourage research for the
benefi t of future patients.
Transnational support to create an international childhood cancer
survivor registries research programme that builds on existing
structures is urgently needed.
Regulatory frameworks All national and international legislative mechanisms (eg, EU 27)
should have formal mechanisms in place to include childhood cancer
research within any impact assessment. Additionally, policy makers
and regulators urgently need to positively engage with the clinical
tri als and population-based research communities as current
legislation is reviewed and updated. Regulators should consider
several additional improvements to paediatric investigation plans:
consideration of the mechanism of action of drug rather than the
adult condition; reconsideration of the waiving process; improved
consideration of what is done and planned in a given paediatric
cancer through drug development strategies established for each
disease; development of paediatric investigation plans that address
several targets from diff erent companies for the same disease; and
developing mechanisms within the paediatric regulatory framework
that prioritise unmet clinical needs, led by the paediatric oncology
community in partnership with parents and industry.
Threats to availability
of data on cancer
Ensure data protection requirements do not jeopardise the ability for
clinical trial groups or national health services to share data for
pooled analyses that contribute to improved patient outcomes.
.. Easy to
Table: Policy priorities for the global childhood cancer agenda
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70007-X
traditional childhood cancer community, and also
leverages the solidarity that exists between all the
communities involved in the care, research, and
education agendas in childhood cancer. The delivery of
improved global outcomes for children with cancer will
need creative policy solutions to many issues, from
fundamental biology to the delivery of new educational
systems for sick children. Agreement, solidarity, and
mutual help will be the most important means to fulfi l
these policy recommendations. In 2023, we should be
able to look back and see real improvements in all the
issues raised in this Series; although many goals are
ambitious, none are out of reach.
RS and KP-J framed the manuscript, and all authors then contributed
Confl icts of interest
We declare that we have no confl icts of interest.
This work has received funding from the European Union’s Seventh
Framework Programme (FP7/2007–13) under the European Network for
Cancer Research in Children and Adolescents project (grant number
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