The Different Phases of Clinical Trials

The development of investigational new drugs (INDs) involves performing clinical trials (or studies) to assess the safety and efficacy of the IND in humans.  These trials are usually classified into 4 phases of development (Phase 1 to 4), with each potentially lasting for several years.  Successful completion of each phase and approval by the appropriate regulatory authority or authorities (the European Medicines Agency [EMA] in the European Union, Food and Drug Administration [FDA] in the United States, Health Canada in Canada, or the Ministry of Health, Labour and Welfare in Japan) is required for progression to the next phase.

Satisfactory completion and approval of Phases 1 to 3 is required for a drug to be approved for marketing.  Phase 4 studies are conducted after a compound has been approved, for the primary purpose of post marketing surveillance.

In an attempt to both speed up the drug development process and to quickly identify safety issues, Phase 0 studies, also referred to as ‘human microdosing studies’ were introduced. 

The different clinical trial phases are described in further detail below and summarised in the table at the end of this blog.

Phase 0

The official name of a Phase 0 study is an exploratory IND study, and the goal is to quickly establish whether an agent will work as desired in humans, based on in vivo safety pharmacology and toxicology preclinical studies.  In Phase 0 studies, a single subtherapeutic dose of the IND is administered to a small number of healthy subjects (c.10 to 15), over a short duration (7 days).  Since the dose administered is too low to result in a therapeutic effect (ensuring the absence of toxic effects), preliminary pharmacokinetic (PK) and, where possible, pharmacodynamic (PD) data are collected for evaluation. 

Phase 1

Phase 1 studies are designed to assess the safety of an IND, to understand its PK and PD properties, and to ideally identify a potential therapeutic dose.  These studies are usually conducted in a small number of healthy volunteers/subjects (c.15 to 30). 

Phase 2

These studies are typically conducted to test the IND in a larger group of patients who have the disease or illness for which the IND is being developed, to determine whether it is efficacious, at least in the short term.  Phase 2 studies are larger than those conducted earlier in the drug development, typically comprising up to 300 patients.

Phase 3

Phase 3 studies are designed and performed to assess the efficacy and effectiveness of an IND in a larger cohort of patients, all of whom have the disease that the treatment is intended to treat.  Such studies are typically conducted in several hundred patients, and are usually conducted at multiple sites in multiple countries.  Phase 3 studies often compare the new treatment versus the current ‘gold standard’ treatment for the condition for which the new treatment is being developed.

Phase 4

Post marketing surveillance involves monitoring for safety (pharmacovigilance) once a treatment has been approved by the appropriate regulatory authority or authorities.  Such surveillance is intended to identify any rare adverse effects that have not been observed previously or have only been observed infrequently, and to monitor the effects of long term administration in a wider population.

* Not always performed

Authors note: This blog was originally published on 25/08/2011 and has since been updated.