Phases of Clinical Trials
Clinical research is performed in distinct segments called phases. Each phase of a clinical trial is designed to provide different information about the new treatment, such as the dose, safety and its effectiveness compared to standard therapy. The phases are described as Ib, II, III and IV.
PHASE Ib TRIALS
These trials usually involve a small number of patients (usually 10 to 20) for whom other standard therapies have failed or no known alternative therapy is available. This phase generally lasts several months to a year. People who participate in phase Ib trials are the first to receive a new therapy or often a new combination of therapies.
In phase Ib trials, the dose of an investigational drug is gradually increased to determine the optimal safe dose. This process is called dose escalation. The first participants (cohorts) are given a small dose of the drug.If there are no or few side effects, the next group is given higher amounts of the drug until the doctors determine the optimal dose; the most effective dose which does not produce unacceptable side effects. The primary goals of this phase are to determine the agents’ anticancer activity in humans, the maximum tolerated dose or treatment, the manner in which the drug works in the body, the toxic side effects related to different doses and whether these toxic side effects are reversible.
Upon completion of phase Ib trials, the researcher should be provided with sufficient information about the drug’s pharmacokinetics and pharmacological properties (safe dose range and adverse effects), to permit designing safe, well-controlled, scientifically sound phase II studies.
PHASE II TRIALS
When the appropriate phase Ib trials have been completed and sufficient safety data are in hand, the phase II trials are initiated.Phase II studies are rigid, well-controlled studies in a relatively small patient population, usually no more than a few hundred subjects in total. These subjects have the target disease. Their purpose is to determine the effectiveness of the treatment in a specific patient population at the dose and schedules determined in the phase Ib trial.The response rate in this phase needs to be equal to or higher than the standard treatment in order to proceed to phase III trials.
PHASE III TRIALS
Phase III trials are only initiated if the data generated in phases Ib and phase II show a satisfactory safety profile and there is sufficient evidence of efficacy. The purpose of phase III trials is to demonstrate the long-term safety and efficacy needed to assess the risk/benefit relationship of the drug and to provide adequate data for the product package insert.
The goal of phase III trials is to compare a new drug or therapy with a standard therapy in a randomized and controlled manner in order to determine the proof of effectiveness. Phase III trials require a large number of patients (often thousands) to measure the statistical validity of the results because patient age, sex, race, and other factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials.
PHASE IV TRIALS
Once the drug or treatment becomes part of standard therapy, the manufacturer of the drug may elect to initiate phase IV trials. This phase includes continued evaluation of the treatment effectiveness and monitoring of side effects as well as implementing trials to evaluate usefulness in different types of cancers.
The new drug may be further evaluated in response to a governmental request to support the NDA (new drug application). Additional safety and/or efficacy data are collected. Testing of a drug may be conducted in search of additional marketing claims, new formulations, and new combinations.