Clinical trials that form part of the drug development process are conducted in progressive phases which are designed to assess a new medicine for safety and effectiveness. Each phase must be successfully completed before the next can begin.
Phase 0 trials are small (10-15 subjects) first-in-human trials. Typically a suboptimal drug dose is tested to generate preliminary data on a drug’s pharmacodynamics and pharmacokinetics.
Phase 1 trials are slightly larger studies (20-100 subjects) spanning several months, with the aim of evaluating the safety and tolerability of the new drug, and determine dosage ranges. These studies can also begin to identify early side effects. Some phase 1 trials are carried out in healthy subjects, others in patients with specific health conditions who are willing to try an experimental treatment. Around 70% of phase 1 trials progress to phase 2.
Phase 2 trials (several hundred subjects) spanning several months to two years, are designed to evaluate the efficacy of a drug in the target patient group. This level of trial is usually randomised, double-blinded and placebo controlled and would be expected to identify further side effects. Approximately 33% of phase 2 trials progress to phase 3.
Phase 3 trials (300-3000 subjects) taking 1-4 years, are designed to confirm the effectiveness of a drug observed in a phase 2 trial. Larger subject numbers increases the statistical veracity of the results. Phase 3 trials will often compare the new drug to existing therapies (active comparators), and will potentially identify rarer side effects. Although effectiveness of a trial drug is best assessed in a large trial, in the case of rare diseases, by definition the available patient cohort limits the size of the trial.
Phase 4 of the clinical trials take place after a drug has been marketed and typically involve post-marketing safety monitoring following use in the general population. This level of investigation provides additional information in respect of the treatment’s risks and benefits, informs its optimal use, and can identify any side effects resulting from long-term use.
This is a narrated slide-set comprehensively covering drug development and regulation, presented at a level for first year medical students. Authored by Prof. Simon Maxwell, University of Edinburgh (s.maxwell@ed.ac.uk).