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CTSU & China: 20 years of collaboration

Jonathan Wood

Currently everyone is interested in China – whether its China’s astonishingly rapid emergence as an economic powerhouse, its place as a huge producer and consumer in a globalised world, its role in global politics, its part in climate change negotiations, or as a stage for a fabulous Olympics.

China is also fascinating from a medical and public health point of view. It goes without saying that China has a vast population of over 1.3 billion. But that population is spread between cold northern latitudes and tropical beach resorts in Hainan, and lives both in underdeveloped rural areas and the crowded international cities of Shanghai and Hong Kong.

It’s also an ageing population, as the effects of the rapid improvement in the general health of its population and birth control policies play out.

Changing lifestyles
On top of all that, rapid economic change has led to equally fast changes in many people’s incomes, diets and lifestyles. As a result, disease patterns have altered remarkably over the past 40–50 years so that chronic diseases such as heart attacks, diabetes and cancer are now the biggest killers rather than infectious diseases and diseases of poverty.

Coupled with relatively well established nationwide healthcare infrastructure, this means China is a very good place to carry out large-scale medical research. Clinical trials of new treatments carried out here, as well as observational studies that can reveal risk factors for chronic diseases like heart attacks and cancer, will be useful not only for public health policy in China but also to inform healthcare in both the developing and developed world.

‘There’s much that we can try to understand. In China there’s a huge unexplained variation geographically in many chronic diseases,’ says Professor Zhengming Chen, director of the China Program at the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford.

‘For example, twenty per cent of adults in rural Sichuan would die in middle age from chronic lung disease back in the 1990s, but deaths from this disease were more than 10-fold lower in many other rural areas. Smoking only accounts for part of this huge variation. Similarly, stomach and oesophageal cancers vary greatly in different regions. There is also a four-or-five fold difference in stroke death rates between different parts of China, with rates in China on average being more than five times as high as in the UK. We’d really like to understand the factors that lead to these differences to inform preventive and therapeutic measures.’

Our news pages announce today that CTSU has just extended and renewed a partnership with Fuwai Hospital of the Chinese Academy of Medical Sciences through the China Oxford Centre for International Health Research. This will further strengthen CTSU’s 20-year long collaboration with medical scientists in China and will provide researchers with dedicated new facilities in China for the next 20 years.

Where it all began
CTSU’s collaborative research with medical scientists at the Chinese Academy of Medical Sciences and the China National Centre for Disease Control started during the early 1980s, initiated by Professor Sir Richard Peto and Professor Rory Collins, co-directors of CTSU.

It began with a landmark study that mapped the regional variation of incidence of chronic diseases, and possible lifestyle and blood determinants of disease rates, at a population level across 69 rural Chinese counties. It grew to include large-scale randomised trials that have resulted in changes to clinical practice worldwide for heart attacks and strokes, and now involves one of the world’s biggest ever blood-based epidemiological studies of the determinants of chronic diseases, involving studying and monitoring the health of over 500,000 people for up to 20 years.

‘We have had the privilege of collaborating with many distinguished medical scientists in China since the early 1980s, probably well before anyone started talking seriously about China,’ says Zhengming Chen. ‘It was not an easy start, and took quite a while to convince many funding agencies and pharma what collaboration with China can really offer.’

That’s changed greatly now that CTSU has demonstrated again and again that you can get collaborative research projects carried out cost effectively in China, with rapid recruitment and high-quality data. These projects have provided clear evidence that can improve clinical practice and save lives. In doing all of this, CTSU has also built up a phenomenal set of partnerships with Chinese research institutions and a network of hospitals across the nation.

One of the early studies that began to change people’s minds was CAST, the Chinese Acute Stroke Trial. Carried out by CTSU and Fuwai Hospital, this looked at whether aspirin as an antiplatelet agent was beneficial if taken soon after the most common type of stroke. Over 20,000 patients from more than 500 Chinese hospitals were randomised to receive either aspirin or a placebo within the first 48 hours of a suspected stroke, at the same time as a similar study was being carried out in the West coordinated by Edinburgh University. This showed definitively that trials could be carried out in China to the same standard as in the West.

‘Even 15 years ago when this was carried out, the number of stroke patients receiving a CT scan in Chinese hospitals was actually higher than in the international study in the West,’ notes Zhengming Chen. The data from both studies were analysed together and showed a clear net benefit for aspirin after a stroke, with the results being published in The Lancet.

More recently, the Second Chinese Cardiac Study (COMMIT-CCS2) involved 46,000 patients from 1250 hospitals in China in investigating the effects of two different emergency treatments for heart attacks. The results, published in 2005 in The Lancet, gave clear evidence for the first time that adding clopidogrel, a new antiplatelet agent, to aspirin can further reduce the risk of mortality for patients after a severe heart attack. The drug is now used in the back of ambulances in many parts of the world.

Biobank reaps dividends
Of all the projects in China involving CTSU, the most impressive so far – in terms of the size, scope and potential scientific significance – is the Kadoorie Biobank Study led by Professor Zhengming Chen at CTSU and Professor Liming Lee in Beijing.

This joint project between CTSU and the China National Centre for Disease Control has $10 million in funding from the Kadoorie Charitable Foundation in Hong Kong, as well as core funding to CTSU from the UK Medical Research Council. It has recruited over 500,000 volunteers over 35 years old from 10 different urban and rural areas across China, and the health of study participants will be closely monitored over the next few decades.

The project started in June 2004 and finished recruiting all half a million volunteers by July 2008. Each of the participants filled out a comprehensive questionnaire on a laptop covering their lifestyle, diet and medical history, completed a range of physical examinations, and provided a blood sample for long-term storage.

This staggering amount of data and the availability of blood samples for later analysis will be an enormously powerful and rich resource in investigating the environmental and genetic causes of many common chronic diseases among Chinese adults over the coming decades. The long-term follow up for deaths and hospital admissions among the 500,000 volunteers has just began, helped by a recent grant of £2.5 million from the Wellcome Trust.

CTSU’s work has shown that high-quality, large-scale medical studies can be carried out in China efficiently, swiftly and economically, providing clear evidence about the efficacy of treatments and revealing risk factors for common diseases. The collaborative centre announced today at Fuwai Hospital will cement this work for the future and add to CTSU’s capabilities in China.