MRC Clinical Trials Unit
Unit profile from the MRC Network publication issued Spring 2005
In 1948, Philip D'Arcy Hart, Director of the MRC Tuberculosis Research Unit, his deputy Marc Daniels and Austin Bradford-Hill, Director of the MRC Statistical Research Unit, published the results of an MRC trial assessing the effectiveness of a new tuberculosis treatment – the recently discovered antibiotic streptomycin. Their study was soon recognised as a milestone in trial design which set the standard for modern randomised controlled trials (RCTs). Under D'Arcy Hart and his successor Wallace Fox, the Unit branched into new areas, including lung cancer trials, and became the MRC Tuberculosis and Chest Diseases Unit (TCDU). After Fox retired in 1986, many TCDU staff joined the MRC HIV Trials Centre, and in 1991 the lung cancer team transferred to the MRC Cancer Trials Office in Cambridge, which had been established in 1977 within the MRC Clinical Oncology and Radiotherapeutics Unit directed by Norman Bleehen. In 1998, the MRC integrated its cancer and HIV trials activities to create a new Clinical Trials Unit (CTU) in London, directed by Professor Janet Darbyshire.
The bulk of the CTU's work is designing, developing and running clinical trials to find better ways to prevent, diagnose, or treat major health problems, in particular cancer and HIV/AIDS. It also has a remit to expand into other areas that do not have a strong tradition of trials, for example arthritis, respiratory disease and blood transfusion. Increasingly, CTU trials are looking beyond whether a treatment is effective to see how it affects patients' quality of life. This is important where small improvements in survival come at the expense of unpleasant or toxic side effects, in end-of-life care and where quality of life is the only difference between treatments. In situations where trials are unethical or impractical, the CTU conducts observational and epidemiological studies to answer important clinical and public health questions. The Unit also evaluates worldwide data from other trials in systematic reviews and metaanalyses. Assessing whether treatments are cost effective is another important consideration, and the CTU collaborates in this area with the Centre for Health Economics at the University of York.
Team CTU
Teamwork is crucial to every aspect of the CTU's work. Its staff of over 100 includes epidemiologists, clinicians, public health specialists, statisticians and other scientists, health economists, trials and data managers, IT specialists and administrators. Furthermore, their success hinges on the cooperation of a wider external community: researchers, doctors and nurses, funding bodies, policymakers and most importantly patients and the public, without whom there could be no trials. The Unit is committed to patient involvement and participation in trials and has well-established relationships with cancer and HIV support networks. It also has close links with the MRC General Practice Research Framework, which is based at the same site.
While the Unit's core activities and many of its trials are MRC-funded, contributions to individual studies also come from the NHS, UK government departments, overseas governments, international agencies, charities, and the pharmaceutical industry. The Unit is becoming increasingly involved in collaborations with industry to develop new drugs in situations where, for example, very large trials are needed, or in uncommon diseases that are not viable commercial propositions. Industrial support, often in the form of free drugs, is also common in CTU trials of untried drug combinations or new uses for existing drugs. But most of the CTU's work is in areas of little or no interest to industry – for example, trials of generic drugs, surgery, radiotherapy and new technologies. All CTU trials retain scientific independence and are overseen by external data-monitoring committies.
Making progress against HIV/AIDS and cancer
The CTU has played an important role in advances in HIV/AIDS and cancer treatments, often through large collaborative studies with other organisations in the UK and abroad. Pivotal early trials showed that AIDS can be held at bay by using a cocktail of anti-viral drugs, and helped to refine multi-drug anti-retroviral therapy (ART). Later CTU studies showed that the advent of ART had dramatically reduced death rates in Europe, Australia and Canada, and halved the rate of progression to full-blown AIDS in UK children. However, most HIV-infected people live in societies that lack the resources and infrastructure to make ART widely available, which is why trials are under way in a number of poorer African countries including Uganda and Zimbabwe to explore ways of making ART more accessible to the patients who live there.
AIDS prevention is a rapidly expanding area of the Unit's work. A recent trial in Zambia showed that a cheap and widely available antibiotic wards off fatal infections in children with HIV-weakened immune systems, cutting AIDS-related deaths by nearly half. As a result, the World Health Organisation and UNICEF are updating their advice on effective medicines for children with HIV. The CTU is also actively involved in work to develop vaginal microbicide agents incorporated into products such as gels, foams, suppositories and sponges for use by women before intercourse to prevent the spread of HIV and other sexually transmitted diseases. Together with Imperial College London, the Unit is leading the Microbicide Development Programme, a partnership of UK and African academic institutions, non-governmental organisations and commercial partners.
Focusing on the most devastating cancers, CTU trials have demonstrated treatment benefits in operable oesophageal cancer, locally advanced bladder cancer and non-small cell lung cancer, and kidney cancer. Recently, data from a CTU trial of platinum-containing chemotherapy given immediately after surgery to women with early ovarian cancer showed that patients' chances of living another five years rose from 70 to 79 per cent. In parallel, international collaborations involving the collection and meta-analysis of data from thousands of patients have confirmed that chemotherapy improves survival in non-small cell lung cancer, invasive bladder cancer and high-grade glioma, and demonstrated harm from radiotherapy following lung cancer surgery in some patients.
Community meeting, Masaka, Uganda: Microbicide Development Programme workers tell local people about the research and how they can take part.
Clinical Research Networks
Recent developments have placed the CTU at the heart of UK clinical research. In 2001, the Department of Health (DoH) selected a consortium involving the CTU and researchers at Leeds and York universities to coordinate the new National Cancer Research Network (NCRN), a major initiative to improve the speed, quality and integration of research, with the ultimate aim of improving patient care. Patient enrolment to cancer trials has already doubled. Building on the NCRN model, in 2004 the DoH set up the UK Clinical Research Network (UKCRN) to strengthen infrastructure and coordinate trials in other diseases as part of the new UK Clinical Research Collaboration (UKCRC). It will encompass existing cancer and mental health networks, and new ones in stroke, diabetes, Alzheimer’s and medicines for children, with others to follow. The CTU is a partner in the consortium selected in January 2005 to coordinate the UKCRN, and Professors Janet Darbyshire and Peter Selby (originally Director of the NCRN) are its co-directors. As Professor Darbyshire told Network: “The UKCRC is the most important development in UK clinical research in recent years. I am delighted to be so closely involved, and that the CTU will play such a prominent role.”