Clinical trials: A lay explanation

Before a doctor can prescribe a medicine to a patient there is a long process of research and development that must first be carried out. Here we describe the different stages of research involved in the development of a drug in language understandable to a lay audience.

Pre-clinical research

The early stages of drug development involve preclinical studies using drug molecules that researchers believe have the potential to effectively treat a disease. These studies are conducted in the laboratory setting in body tissues/cells (known as in vitro studies) or in animals or humans (in vivo studies). The purpose of these studies is to find out if the drug might cause serious harm if given to humans (known as toxicity). After reviewing the results of preclinical studies, researchers decide whether to test the drug in humans in clinical trials.

Phase 1 trials

Phase 1 trials are small studies in fewer than 100 humans that last for a relatively short period of time (e.g. a few weeks or months). Participants in these studies are a mix of people who have the disease of interest as well as people without the disease. The purpose of Phase 1 studies is to find out if the drug is safe for humans to take and to get an indication of which dose of the drug might be most appropriate.  Approximately 70% of drugs tested at this stage will progress to the next stage of research.

Phase 2 trials

Phase 2 trials are larger studies in up to a few hundred patients who have the disease of interest. These studies typically last from a few months to up to two years. The purpose of Phase 2 trials is to find out if the drug is effective at treating the disease in question and to identify the drug’s side effects. Around one third of drugs tested in Phase 2 trials progress to the next stage.

Phase 3 trials

Phase 3 trials are larger studies of a few hundred to up to a few thousand patients with the disease of interest that last for between one and four years. The purpose of these studies is to further assess the effectiveness of the drug for treating the disease and to monitor rates of adverse reactions in patients. In Phase 3 studies the drug of interest is usually compared with either another drug that is widely used to treat the disease in question, or with a placebo (i.e. a control treatment that does not contain any drug molecule). Findings from Phase 3 trials provide key evidence that is used by regulatory bodies to decide whether a drug will be allowed to be prescribed by doctors for specific diseases (known as ‘approval’).

Phase 4 trials

Phase 4 trials are done after the drug has been shown to be safe and effective and once the drug has been approved by regulatory bodies for use in patients. These are large-scale long-term studies conducted to monitor ongoing drug effectiveness and safety, and to determine the long-term balance between benefits and risks of the drug.