Drug Development

The clinical stages of drug development are traditionally divided into:

• Phase I. Phase I trials involve between 20 and 80 healthy volunteers and include initial single dose 'first into man' studies followed by repeated dose studies. The objective is to investigate a drug's pharmacokinetic (absorption, distribution, metabolism and excretion) and pharmacodynamic (beneficial and adverse effects) properties. Average duration: six months to one year.
• Phase II. Phase II trials usually involve 100 to 200 patients. The principal objective is to determine the drug's effectiveness ('proof of concept') and dose-response relationship in the target population to determine the optimal dosing regimen for confirmatory Phase III studies. Average duration: one to two years.
• Phase III. Phase III trials involve several hundred to several thousand patients. The principal objective is to verify efficacy and to describe the safety of the drug in the target patient population. Average duration: two to three years.
• Phase IV. Phase IV trials begin after regulatory approval and typically are used to evaluate new indications, new dosage strengths or formulations. They may be required to show cost-effectiveness or to provide information on long-term safety

The ultimate goal of this resource-intensive activity (Fig 7) is to develop a a medicinal product that will be not only safe and effective but also practical. For example, a new treatment for Alzheimer's disease, which needs to be given chronically but can only be given by continuous intrathecal injection, is very unlikely to be viable as a medicine, even if it is effective in clinical trials. The combination of efficacy, safety and practical considerations mean that less than a quarter of the drugs that enter Phase I eventually gain a license. The requirements for manufacturing of pharmaceutical products are very stringent and ensuring consistent compliance with these requires considerable ingenuity and resource.