The phases of the clinical Trial
Phase I trials start with the initial administration of an investigational new drug into humans to evaluate its safety, determine a safe dose range, and identify side effects.
The study is also designed to define the recommended dose for further evaluation.
Throughout Phase I trials, researchers monitor whether the new drug shows any effect against cancer. However, as these trials are often testing drugs for the first time in people, the goal is to find out how to administer the drug safely, and not how well it fights cancer.
A Phase I trial usually enrols only a small number of patients (sometimes less than 20). Usually patients who have already taken standard treatments without success and do not have other effective cancer treatment options are eligible to participate in a phase I trial. Phase I studies offer a unique opportunity to be treated with a brand-new agent, when there is non effective treatment left.
Typically, patients in phase I trials are divided into cohorts (small groups of patients), usually around 3 patients. The first cohort receives a low dose of the new drug. Researchers may collect blood or urine samples to measure drug levels in the patients. If no severe side effects occur, then a new cohort receives a higher dose of the same drug. The dose increases with each new cohort until the researchers see too many side effects or until they determine the best dose.
If a new treatment is found to be reasonably safe in a phase I clinical trial, the treatment can then be tested in a phase II trial.
Phase II Trial
Phase II trials explore the efficacy of the treatment in patients in terms of tumour regression and continue to test safety.
They usually focus on a particular type of cancer. Less than 100 patients usually participate in a phase II trial.
Patients who volunteer to participate in a phase II trial may have been treated with chemotherapy, biotherapy, surgery or radiation and still need further treatment. Only one-third of experimental drugs successfully complete both phase I and phase II trials.
If the new treatment seems to be effective against cancer in a certain percentage of patients, researchers may consider it successful enough to continue investigation in a phase III clinical trial.
Phase III trial
Phase III trials aim to demonstrate, or confirm a therapeutic benefit. In these studies, the new treatment(s) is (are) compared to the current standard treatment.
Most phase III studies are randomized and blinded trials. A Phase III trial usually enrols a large number of patients.
Relying on the results obtained after phase III, the pharmaceutical industry can submit an application for marketing approval to the relevant health authorities.
Phase IV trials
Studies in Phase IV are all studies (other than routine surveillance) performed after drug approval and related to the approved indication.
They are studies that were not considered necessary for approval but are often important for optimising the drug's use including its risks and benefits.