Annals of Oncology
Developing innovative models for NorthSouth cooperation in clinical researchexperience from the INDOX Cancer
Research Network
R. Ali and V. Raina
Ann. Onc. 19:831-833, 2008. First published 5 Mar 2008;
doi:10.1093/annonc/mdn034
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editorial
Developing innovative models for
North–South cooperation in clinical
research—experience from the INDOX
Cancer Research Network
Cancer, long thought of as a disease of richer, industrialised
and high-income nations, is now the second leading cause
of death in many lower income countries. More than 50% of
the world’s cancer burden, in terms of both numbers of cases
and deaths, occurs in developing countries and is rising [1].
More particularly, some 45% of >1 million new cases of breast
cancer diagnosed each year and >55% of breast cancer-related
deaths occur in low- and middle-income countries [2, 3].
By 2020 it is estimated that 70% of all cancer cases will be in
these lower income countries—and approximately one-quarter
of these will be in India, with its (still increasing) population
of over a billion [1].
India is experiencing rapid demographic, socioeconomic and
risk factor changes, particularly in urban areas, leading to an
alarming rise in the incidence of chronic diseases such as
diabetes, hypertension, heart disease and cancer. As the
epidemiological transformation gathers pace, the incidence of
cancer is expected to double in the next 10 years to 2 million
cases a year [1]. Changes are also occurring in the relative
incidence of different cancers with stomach cancer in men
and cervical cancer in women decreasing (traditionally cancers
of low-income countries) and some tobacco-related cancers
and breast and endometrial cancers in women and prostate
cancer in men increasing (traditionally more common
cancers in high-income countries (Table 1).
As the mortality and morbidity from cancer increases in
India, there is an urgent need for clinical research into the
treatment and prevention of those cancers [4]. As far back as
1993 in an Annals editorial, Tobias and Mittra [5] recognised
that, ‘Perhaps the greatest handicap that developing nations
face in their fight against cancer is the lack of an adequate
research base’. Suitable training opportunities for principal
investigators, junior doctors and research nurses have also
been lacking.
Even as India has been attracting a large number of the
number of clinical trials in the last decade, the vast majority of
these have been designed outside of India by either Western
academics or pharmaceutical companies with little or no input
from Indian investigators. These trials have tended to focus
on cancers of primary interest to developed nations using
India simply as a place to recruit extra patients. As Masera
and Biondi [6] called for: ‘Research in the South should be
conducted by investigators from the South, on persons from
the South, and for the good of the people of the South, with the
ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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Annals of Oncology 19: 831–833, 2008
doi:10.1093/annonc/mdn034
Published online 5 March 2008
main goal not being to solve the North’s problems. Close
interplay is needed between North and South in drawing up
research methods and mobilising resources to conduct
investigations.’ Unfortunately, the country also suffers from
a shortage of properly trained specialists in cancer—there are
editorial
<150 properly trained medical oncologists and <100 dedicated
surgical oncologists. The situation regarding radiation
oncologists is slightly better with 1000 of them qualified
but many public sector hospitals do not have modern
radiotherapy equipment. In many of these hospitals,
chemotherapy is still practised by radiation oncologists, as
departments of medical oncology have not been created.
In order to tackle some of these problems, as reported in
Annals in 2005, a new partnership was established between the
Institute for Cancer Medicine, Oxford University, and six
leading cancer centres in India, the INDOX (INDia–OXford)
Cancer Research Network, with the assistance of an
educational grant from GlaxoSmithKline (Figure 1) [7]. ‘So
two years on, what has been achieved—have the network’s aims
been realised and what challenges remain?’
The INDOX network’s initial priorities were to improve the
clinical research infrastructure at the Indian centres as well as
the skills and expertise of researchers in India. Although all the
Indian principle investigators were senior professors with
extensive clinical trial experience, training of more junior staff
as well as research nurses and trial pharmacists had been far
more limited. Phase 1 trial experience was virtually non-
existent as phase 1 trials with foreign molecules had not been
allowed in India until 2005 and Indian pharmaceutical
companies had previously concentrated solely on producing
generic drugs.
Another aim of INDOX was to ensure that Indian
clinicians were involved in clinical trial design from the outset,
working with the sponsor to ensure that protocols were
developed which are practically suited to be carried out on
patients in India with appropriate eligibility criteria and in
those cancers which are common in India.
progress to date
There were a number of practical problems we faced in the
initial stages with one of the major challenges being able to
recruit and retain high-quality clinical research staff to run
the trials. Dedicated site coordinators were therefore
appointed at all six centres and a comprehensive training
program was established for all staff involved in clinical trials
consisting of multidisciplinary seminars, workshops and
courses held in both Oxford and India.
A fellowship scheme was also setup with a number of 1-year
clinical research fellowships leading to a diploma in clinical
editorial
trials and short-term visiting fellowships were awarded
annually. The training and fellowship scheme has proved
extremely popular and a total of 24 research staff including
principal investigators, sub-investigators, site coordinators and
research nurses from all six sites have now attended clinical
trials training sessions in Oxford. The fellowship scheme has
also been successful in reducing the staff attrition, which was
one of the main problems sites were facing in building effective
clinical trial units.
All centres now have dedicated clinical trial units and are
equipped to conduct trials to international Good Clinical
Practice (GCP) standards with India-specific Standard
Operating Procedures (SOPs) being implemented across all
sites. To date, a total of eight trials in all phases have been
conducted through the INDOX network and >100 patients
have been recruited. Two INDOX sites also participated in our
first phase 1 trial, which was one of the first to be approved by
the Indian regulatory authorities using molecules developed
outside India.
Our experience with the regulatory authorities has been
mixed—in general the Drugs Controller General, India, has
been very supportive of our efforts, but due to staff shortages
and reorganisation, approvals have sometimes been slow.
There, however, have been some positive regulatory
developments during the last 6 months and a new system has
now been put in place whereby new trial applications are being
processed more efficiently.
ethical concerns
Much has been written about the ethical problems arising as
a result of the rapidly increasing number of clinical trials being
conducted in India with inadequate regulatory oversight [8, 9].
Our primary concern has always been to ensure that trials are
conducted according to the highest ethical standards and all
Table 1. Most common cancers in India (data from Indian cancer
registries)
Most common cancers in Most common cancers in
India: males India: females
Lung Breast
Larynx Cervical
Stomach Oesophagus
Lymphoma Ovary
Prostate Head & Neck
Figure 1. Sites and principal investigators in the INDOX Cancer Research Network.
832 | Ali & Raina
Annals of Oncology
trials are approved by local ethics committees. However, we
recognise that some ethical problems remain, particularly
considering that a substantial proportion of the population are
illiterate and ill-informed about medical research and it is
therefore difficult to ensure that those who agree to take part
in trials are both fully informed of and understand the risks
and benefits of doing so. In the public sector, there also still
tends to be a somewhat paternalistic doctor–patient
relationship, leading to possible exploitation. Widespread
poverty means that the usual standard of care is unaffordable
to many, leading to possible inducement. These problems
are, of course, not exclusive to India, but to address some of
these issues further, we are planning to undertake India’s
first national and the largest ever survey of clinical trial
participants to assess their motivation for taking part in the
trials and how informed their consent really is.
We are also aware of the need that trials be relevant to the
population in India and that there is a realistic prospect of
these therapies being available to not just a small minority of
patients in India once trials are completed.
future plans
To tackle India’s increasing cancer burden it is of course
necessary not only to undertake clinical trials using drugs
developed in the West (which may be beyond the means of
a large proportion of the population) but also to investigate
whether alternative cheaper therapies are effective in treating
different cancers. There continues to be widespread use of
traditional Ayurvedic medicine among the Indian masses
and we plan to undertake randomised controlled trials of
some of these therapies to assess their true effectiveness in
clinical practice.
Unfortunately, there are no national or statewide screening
programmes for common cancers such as head and neck, cervix
and breast. We therefore recognise the need to address
prevention and are beginning to conduct epidemiological
research into the causes of cancer in India. There is a need to
investigate the importance of various risk factors and
opportunities for prevention in those cancers, which are
more prevalent in India (e.g. head and neck, cervix
and gall bladder) as well as those, which are beginning to
increase with changing lifestyles (e.g. breast and colorectal).
We also wish to expand the network to 12 sites and would
like to include cancer centres in the east of India and rural areas
which are densely populated and where clinical research has
been neglected. There are also plans to work with sponsors
Volume 19 | No. 5 | May 2008
Annals of Oncology
to support investigator-initiated trials and so make greater use
of the huge intellectual capital within the network.
conclusions
Over the past 2 years, INDOX has established itself as one of
India’s leading oncology networks as reflected by the
enthusiasm of other centres in India to join us. It is a true
partnership and a good example of how collaboration between
Indian and Western academic institutions and the
pharmaceutical industry can benefit all parties involved. Of
course, much remains to be done—cancer in India is a huge
and increasing problem—but we have made a start and with
continued support from both the private and public sector
there is huge opportunity to improve the lives of millions of
people. We believe that similar models of North–South
cooperation could be successful in helping to tackle cancer in
other developing countries.
R. Ali1* & V. Raina2
1
INDOX Cancer Research Network, & Department of Clinical
Pharmacology, University of Oxford, Oxford, UK
Volume 19 | No. 5 | May 2008
editorial
2
Department of Medical Oncology & Delhi Cancer Registry
Institute Rotary Cancer Hospital, All India Institute of
Medical Sciences, Delhi, India
*(E-mail: raghib.ali@clinpharm.ox.ac.uk)
references
1. Stewart BW, Kleihues P. World cancer report. Lyon, France: International Agency
for Research on Cancer & World Health Organization 2003.
2. Curado MP, Edwards B, Shin HR et al. Cancer incidence in five continents, Volume
IX. Lyon, France: International Agency for Research on Cancer 2007(eds)(IARC
Scientific Publications No. 160).
3. Porter P. ‘‘Westernising’’ women’s risks? Breast cancer in lower-income
countries. N Engl J Med 2008; 358(3): 213–216.
4. Strengthening clinical research in India. Lancet 2007; 369: 1233.
5. Tobias JS, Mittra I. Improving cancer care worldwide. Ann Oncol 1993; 4:
283–287.
6. Masera G, Biondi A. Research in low-income countries. Ann Oncol 1999; 10:
137–138.
7. Raina V. Doing cancer trials in India: opportunities and pitfalls. Ann Oncol 2005;
16: 1567–1568.
8. Srinivasan S, Loff B. Medical research in India. Lancet 2006; 367: 1962–1964.
9. Nundy S, Gulhati M. A new colonialism? Conducting clinical trials in India. N Engl J
Med 2005; 352: 1633–1636.
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