MRC Clinical Trials Unit at UCL

Many of our studies of infectious diseases are international collaborations that aim to reduce the burden of life-threatening illness on people living in resource-poor communities. An example of this is a series of trials looking at the use of cotrimoxazole, carried out in partnership with researchers in several African countries. The CHAP trial, published in 2004, showed that cotrimoxazole prophylaxis in HIV-infected children not on antiretroviral therapy reduced deaths by 43%, and hospital admissions by 23%. The study results had an impact on HIV treatment guidelines around the world. Building on these results, within one of four randomisations, the ARROW trial investigated whether it was safe to stop cotrimoxazole prophylaxis for children on antiretroviral therapy, as guidelines at the time suggested. ARROW found that hospitalisations for infections were 4% higher in children who stopped cotrimoxazole than those who continued it, and health economic work revealed that cotrimoxazole prophylaxis was cost-saving. These results are now reflected in the World Health Organisation guidelines. Now the TRACT trial is investigating whether HIV-negative children with severe anaemia also benefit from cotrimoxazole prophylaxis.

The MRC CTU at UCL is at the forefront of developing new, more efficient trial designs. One of these innovations is the multi-arm, multi-stage (MAMS) design. This allows several new treatments to be compared against a single control arm, and seamless progression from Phase II to Phase III trials. Arms can be dropped early, due to insufficient activity, or added as new treatments become available for testing. The STAMPEDE prostate cancer trial uses the MAMS design. It started with six arms, but has since dropped two, and added a further three. STAMPEDE will evaluate eight treatments in 15 years, which would, in separate two-arm trials, have taken more than 40 years.