Phases of drug trials
Clinical trials of drugs and biologics are conventionally described as phase 1, 2, 3, or 4.[10,14] The phase of trial depends on the function of the trial and timing with respect to its approval. One distinction is that phase 1-3 trials are typically conducted prior to approval of a drug for market entry, while phase 4 trials are postmarket studies. While classification of drug trials into phases is useful, in practice trials do not always fit into mutually exclusive categories.14
Phase 1 trials are small studies of about 20 to 80 patients used to characterize the toxic and pharmacologic effects of a drug, such as dosages that can be safely tolerated, although phase 1 trials may also in some cases provide preliminary information about drug activity.10,14 While phase 1 trials are conducted among healthy volunteers for many types of drugs, these trials may also be conducted in patients who have not responded to existing therapies as occurs in oncology research.14
Phase 2 trials are studies of about 100 to 300 patients which are used to test the efficacy of a new drug and provide additional information about drug safety.10 A comparison may be made with a concurrent control group or historical controls or between the pre- and post-treatment periods. As studies of this size have less statistical power than larger studies, assessment of treatment effect tends to rely on measures such biomarkers or less definitive clinical outcomes.14
Phase 3 trials are randomized controlled trials conducted in a larger group of patients, such as 1000 to 3000 or more, which provide a more valid assessment of drug efficacy and safety than earlier phase trials.10 Conventionally, evidence from phase 3 trials has been required for market approval of drugs in countries like Canada and the US, although in some cases approval may be based on phase 2 trials without phase 3 trials having been conducted.14,15
Phase 4 trials serve to provide information about drug adverse effects after a drug has entered the market. This is important because some adverse effects may take years to develop and some adverse effects are rare and might not become apparent until a drug is used by a larger number of people or in a broader range of patients.10