Translational research - from preclinical to clinical studies
Consider the definition of translational research provided by the National Institutes of Health (8):
To improve human health, scientific discoveries must be translated into practical applications. Such discoveries typically begin at “the bench” with basic research — in which scientists study disease at a molecular or cellular level — then progress to the clinical level, or the patient's “bedside.”
The translational research process is long and complex. Developing a new drug or device can take from 4 to 20 years. It can take up to 3 years before an experimental agent is ready for testing in people. The National Institutes of Health, National Cancer Institute, and others are looking for ways to accelerate the process.
I. PRECLINICAL STUDIES test agents in cancer cell lines, tissue and fluid samples, and small laboratory animals. Preclinical studies help researchers estimate a safe starting dose for clinical trials in people.
II. TESTS IN PEOPLE progress through the following continuum, or series of phases.
Phase 0 studies were recently introduced to save time in learning if a new agent will affect the intended cancer-related target. Phase 0 trials enroll 10 or less patients and use smaller doses of an experimental agent over a shorter period of time. The doses are too low to be therapeutic, but large enough to make an impact, and risk of harm is minimal. In Phase 0 studies there is no control group.
Phase I studies help determine the safest dose and method of delivery. There can be as few as 12 or as many as 100 participants in a Phase I study. Generally there is no standard-of-care comparison.
Phase II studies continue to test safety and begin to show how well the new agent works. The number of participants rarely exceeds 200, and usually there is no “standard-of-care” comparison.
Phase III studies compare whether the new agent is better than the current standard of care. Phase III studies confirm side effects and establish a safety profile. Patients usually are assigned randomly to one of two groups:
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- Standard of care (control)
- New treatment (experimental).
- Random assignment, or randomization, is important because it gives each patient an equal chance to be picked for either group. As many as 3,000 patients may enroll, and the study often includes many sites nationwide.
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Phase IV studies focus on new agents that were approved based on results of prior clinical studies. Phase IV provides additional information on responses, risks, and benefits.
