New products — clinical trials

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Phase I

Once the pre-clinical phase is completed, a clinical trial application can be made. Phase I clinical trials begin where potential new medicines are used in 50 to 100 human volunteers to see how the drugs are metabolised. From the original 10,000 interesting compounds, there may be only eight to 15 left at this stage — during phase 1 another four will fail.

Phase II and III

In phase II clinical development, the drug will be used for the first time in a small group of 200 to 400 informed patients to establish therapeutic efficacy at various dose levels. At the close of this phase, more compounds will be rejected leaving only four compounds to enter large-scale development in phase III. This is the largest and most expensive stage of development where full randomised trials are conducted in over 3,000 to 4,000 patients, often on a worldwide basis.

The exact number often depends upon the therapeutic area, the administration route, and the incidence and prevalence of the disease. Phase III is the most difficult stage of drug development. It takes many years for the studies to be completed under strictly controlled circumstances and for the results to be tabulated and analysed. The data from the variety of centres will form the backbone of clinical experience with the new chemical entity, to support regulatory requirements. Double blind comparative studies are performed to a standard that will satisfy the most rigorous needs, so that an international regulatory dossier (IRD) can then be created.

Phase IV

Local regulatory submissions are based on the IRD, with the addition of any special data required by each regulatory body. Vast amounts of data have to be sent to the Medicines and Healthcare products Regulatory Agency and European Medicines Evaluation Agency with a delay (often of up to two years) before any licence is granted. Studies do not stop there and continue after licence into phase IV where post-marketing evaluation studies monitor both clinical effectiveness and side effects that might occur after prolonged use in a larger number of the wider population.