of the drug. Clinical trials conducted without the goal of regulatory approval (e.g., government sponsored) might test a drug or intervention in a diverse group of study participants, include a long time frame for follow-up of study subjects, and address a broader set of questions. The workshop examined a variety of clinical trials, including those sponsored by industry and government, but the focus was on large, multicenter trials.

The clinical trials process for gaining regulatory approval of a new drug has traditionally been described in five discrete phases. Each phase seeks to answer a different set of questions. An increasing number of volunteers are included in each phase as the trial progresses and attempts to build a case that an experimental drug or treatment is safe and effective against the disease or condition it is intended to treat.

Phase 0 trials are exploratory, first-in-human studies designed to determine whether a drug affects the human body as expected from earlier preclinical, animal studies. These trials involve a small number of people (10–15) who receive a low, nontherapeutic dose of the investigational drug. These preliminary trials help companies rank a number of different drug candidates in their pipeline and make decisions about which candidates should be developed.

Phase I clinical trials test an experimental drug or treatment for the first time in a small group of people (20–80) over the course of a few weeks or a month. Their goals are to assess the safety of the drug or treatment, find a safe dosage range, and identify any side effects.

In phase II trials, a larger group of people (100–300) receives the experimental drug to determine whether it is effective and further evaluate its safety. These trials involve subjects with the target disease and usually last months.

Once preliminary evidence from phase II reveals that a treatment is effective, phase III trials are designed to fully examine the risk/benefit profile of an experimental drug or treatment and test it over a longer period of time in a broader population (1,000–3,000). Because these trials are the last phase in the preapproval process, they are often referred to as “pivotal” trials.

Phase IV, or post-marketing, trials take place after a drug has been approved. They provide additional evidence on the risks and benefits of the drug or treatment and how it can be used optimally.



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