Clinical Trial Terms: Phases

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Different phases of clinical trials have different purposes, and each phase helps investigators resolve specific questions.

Scientific, well-controlled clinical trials are what propel medicine forward and they are absolutely crucial in that regard. When looking for a clinical trial that is testing a drug or therapy for cancer, use the National Cancer Institute's clinical trial search engine.

Phase I Trials

Phase I clinical trials involve a very small number of people, generally somewhere between 20 and 70. Although not true in cancer clinical trials, participants in phase I trials are often healthy volunteers. The goal of a phase I trial is to test how a newly created drug will act in human beings. Investigators want to know how safe the drug is and what dosages represent safe levels. Put another way, investigators want to know what the maximum tolerated dose for the drug is that does not created unacceptable side effects.

Phase I trials are designed to better understand the drug, not to provide any direct benefit to those involved, although in cancer trials, the drug's effectiveness may be considered a secondary endpoint. This trial represents the first time human subjects will ingest the experimental drug. For that reason, phase I trials are the beginning of 'clinical research', or research that involves testing in people.

Phase II Trials

Phase II trials will involve drugs the dosages and side effects of which are well understood. Generally recruitment for phase II trials are larger (in the low to mid hundreds), and in phase II trials for cancer drugs the volunteer subjects are going to be patient volunteers who might benefit from participating, and to what extent they benefit will likely be considered among the primary endpoints.

Phase III Trials

Ideally, a phase III trial would recruit at least 1,000 or more people, although this is not as common in cancer drug trials as it is in drugs for other conditions. The phase III trial pits the effectiveness of the study drug against a comparator, generally whatever the current standard of care is. For instance, rituximab is the standard of care for maintenance therapy in follicular lymphoma; so if the study drug was designed for this setting, the trial protocol would split the participants into two groups, with one receiving the study drug and the other receiving rituximab. Neither the patients nor the investigators should know who is getting which drug (known as 'double blind') so as render the results as free of bias and as objective as possible.

Sometimes a phase III trial is called a 'pivotal phase III trial'. In reality all phase III trials are pivotal trials—which means that the trial is designed to serve as evidence of the drug's efficacy when the drug company applies for marketing approval of the drug to a regulatory agency such as the US Food and Drug Administration.

Phase IV Trials

Phase IV trials are trials that are supposed to be conducted following regulatory approval that either bolster previously submitted evidence of efficacy or allow investigators to further assess the risks, benefits, and optimal usage of the drug. The FDA often requires phase IV trials when it grants conditional approval to a new drug; it believes that the new drug can help people right away, but it wants to see more testing of the drug at the same time.

Source: FDA, NCI, NIH

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