CENTRE FOR DRUG SAFETY SCIENCE

It is estimated that adverse reactions to drugs constitute the 4th most common cause of death in the USA. In the UK, adverse drug reactions (ADRs) are a financial burden on the health services, a major cause of drug withdrawals for the pharmaceutical industry and a life-threatening experience for some patients. A recent survey indicated that 6.5% of hospital admissions were due to ADRs costing the Nation #466 million annually. With the increasing emphasis on polypharmacy and multidrug combination therapy, this situation is set to worsen. At the individual level, whilst many ADRs are relatively mild and self-limiting, in some cases ? in particular the allergic or hypersensitivity reactions ? they can result in permanent disability or fatality. Several recent high profile incidences of adverse drug reactions, for example the withdrawal of Vioxx (a COX2 inhibitor) because of heart attacks and the TGN1412 incident in Northwick Park in 6 healthy volunteers, have undermined confidence in existing preclinical testing procedures, and subsequent safety assessment in man. Despite this, our understanding of ADRs and the mechanisms underlying them are seriously deficient. ADRs are complex biological events which require broad-based expertise and meticulously conducted clinical studies to address. The Centre for Drug Safety Science will provide a unique infrastructure for studying the mechanisms of ADRs and will provide a focus for establishing the critical mass of expertise required to make a real impression on the incidence, prediction and management of such reactions, both within the health services and pharmaceutical industry. Our mission therefore is to create a world-class centre for the investigation of fundamental mechanisms by which adverse drug reactions which are important in our clinics and hospitals, with the overall aim of preventing such reactions through (a) better design of drugs, (b) identifying the factors by which ADRs only occur in some patients, and (c) develop better tests to identify these ADRs early before the reactions develop or become more severe. Another important effect of creating the Centre will be to increase scientific expertise in this area which is important for our healthcare system, regulatory agencies and pharmaceutical industry.

We propose to create a Centre for Drug Safety Science at the University of Liverpool, in collaboration with the University of Manchester, the MRC Toxicology Unit in Leicester, the Medicines for Healthcare products Regulatory Agency (MHRA) and Pharmaceutical Industry. This will provide a centre of excellence for research into drug safety, which is important because: (a) adverse reactions to drugs are common accounting for hospitalisations, visits to GPs and in some cases, patient deaths; (b) drugs continue to be withdrawn from the market because of safety concerns with adverse economic consequences and reduced expenditure on future R & D; (c) the number of new drugs coming onto the market has been poor over the last decade; and (d) the combination of drug withdrawals and lack of new drugs will adversely affect drug choice for patients.

Our mission in the Centre will be to enhance drug safety by developing a facility that will enable research that goes from the laboratory bench to the patient bedside (and vice versa) to identify, evaluate and understand the fundamental mechanisms of adverse drug reactions. We have a 20-year track record of research in this area. The Centre will allow us to consolidate and strengthen this expertise, and will have an unrivalled breadth of research ranging from fundamental cellular processes through animal physiology and pathology to modelling and human population studies, inter-linked in a real sense to add value to research into drug safety science right through from molecule to man. We believe that with Centre status we will be able to compete at the highest levels internationally in undertaking translational research in drug safety for the benefit of patients, the public, the industry and regulators. We have several objectives for the Centre: (a) enhance the safety of medicines; (b) provide new knowledge that informs the design and development of medicines in the future; (c) provide an environment for collaboration between scientists from Academia, NHS, Government and Industry; (d) facilitate training for safety scientists from both clinical and basic backgrounds; and (e) provide impartial advice to all relevant stakeholders.

Most importantly, we believe that a fundamental understanding of the mechanisms of adverse drug reactions will serve to inform the patient, the doctor and the medicinal chemist about the risk-benefit of new medicines and through this make drug therapy safer. This is the ultimate aim of our proposed Centre for Drug Safety Science.