There are several phases of clinical research, aimed at making the safety and efficacy testing process of drug development safer and more rigorous.
Target Selection This stage of drug development aims to identify targets that may be effective for treating the condition of interest. This also allows the exclusion of targets that may not have good success rates and so helps direct limited resources in likely productive directions.
Preliminary safety and toxicology This stage of testing aims to identify whether the drug is safe in animal models. These model organisms may have the condition being studied present within them, such as through the use of transgenic mice. Typically, this stage involves both rodents and mammals (beagles, marsupials, monkeys). Additional steps, such as receptor occupancy studies, can be added here to provide additional safety data to obtain regulatory approval for human trials to begin, however these are not legally required and therefore are not always completed.
Phase I The first stage of testing a drug in humans. A small group of individuals have the drug administered, with a number also having a placebo. After numerous issues in this phase, a pair of participants are selected to have the drug first, with one being administered the active drug and the other a placebo. By then allowing time to confirm there is no immediate adverse reaction, the safety of the trial is improved. If the results of this phase demonstrate the drug is safe, then the trial is allowed to continue on to phase II. This phase may be with healthy individuals not presenting with the target condition, or in some circumstances with the condition (but this is not necessary as this stage is solely to determine that the drug is safe).
Phase II The second phase of the drug trial aims to identify whether the drug is effective and has an impact on the condition of interest. By enrolling a larger group of participants, with the condition, the efficacy can be determined. However, this phase only provides preliminary efficacy data and so phase III trials must be used to make these results more robust. During this phase the safety profile of the drug is evaluated further, and due to the larger group of participants, more side effects are likely to arise.
Phase III This is the final stage of drug testing, identifying further side effects due to the larger group of participants, and providing more integrity to the efficacy of the drug. After this phase of the trial concludes, the data is sent to regulatory agencies (US FDA, EMA, MHRA, …) to approve the drug and authorise market usage.
Phase IV This stage of drug release occurs after it has been released for market use. Post-marketing surveillance monitors the drug for side effects or other adverse events that may occur through the course of the drug’s use. This is particularly important with identifying long-term and rare side effects. Poor results in this phase have led to drugs being withdrawn from the market, including thalidomide during the 1970s.