How does a clinical trial progress from basic concept to an approved treatment? What is meant by Phase I, II, and III?
Margaret Mooney, MD
Senior Investigator, Clinical Investigation Branch
National Cancer Institute
Usually a clinical trial is actually the one of the last steps in a very long process of evaluation of a new treatment and a new drug or a new therapy. It begins with painstaking research in the laboratory. Development of new drugs in the laboratory then usually proceeds to testing in animals. Once testing is shown to be safe and potentially effective, then it is moved into clinical trials which are trials on voluntary human subjects. At that point, particularly in drug development--I am using that as an example--, there is a phase of clinical trials that a drug goes though in terms of evaluation. The first is something called a phase I trial, and in that trial the main goal or objective is to really try and figure out whether the drug is safe and at what doses is it safe and how is it best delivered. The second phase in that development and process is something called a phase II trial. In those types of trials you also continue to develop and to monitor the safety of the drug, but you are also trying to figure out if it is effective agonist a particular type of cancer. If the results of the phase II trials are promising, in both the terms of safety of the drug as well as in terms of effectiveness in terms of a particular cancer, then it moves into what we think of a final stage, which is a phase III testing.
Phase III clinical trials are large trials usually involving hundreds if not thousands of patients in which we are trying to test weather a new cancer therapy or procedure is better or better tolerated than the standard of care for that particular disease. They are usually conducted in multiple institutions across the United States, and the reason that there are so many patients involved or volunteer for these trials is so that we can have a high degree of confidence once the trial is over, and when we evaluate the results, whether the new treatment should replace the previous treatment.
Why do some people chose to participate in clinical trials, while others decline?
I think that there are a lot of reasons that people don't participate in clinical trials. One is that there are some myths about participating in trials. People sometimes think that they are going to be treated with a placebo, or essentially no treatment, and that is almost never done in cancer treatment clinical trials. Another myth that I think prevents people from participating in trials that they feel that they will be treated like guinea pigs. And usually what we find when we talk to people who have participated in trials is that they felt quite the opposite, that they felt empowered by participating in a clinical trial. That they felt what they learned in participating in the clinical trial and though the care that they had received, they felt that they understood more about the disease, and about the options of standard care as well as potential new treatment.
There is really a whole system of protections in place for to protect the rights and the safety of anyone who participates in a clinical trial.
I think that the heart of safety, as well as insuring that a person understands what they are getting to when they participate in a clinical trial, is the informed consent process and that happens at a very local level between the person who potentially participates in the trial and the particular research team composed of the physicians as well as nurses and any other health care professionals at that institution that will be conducting the trial.
In that process the patient learns not what only is the purpose of that trial is but also what the risks and the potential benefits of participation. And it is important to remember that that process is not only a one time process--it is an on-going process as people continue with participation and clinical treatment trial. Particularly in cancer, but in any disease they are informed at all points as to what is happening, of the results of tests that are being taken during that to monitor the progress of that treatment. And at the same time as any safety issues come up, they also are made aware of those issues by the research team.
Patients and potential participants should also realize that their participation is completely voluntary, not just at the beginning, but anywhere in the process. They can decide at anytime to stop participating in a trial if they feel uncomfortable or if they no longer--for what ever reason--want to continue to participate. Their medical care will not be effected at all by there choice.