Phase Stage of Clinical Trails
Before a new drug is allowed to test their treatments on humans, it goes through lab studies or pre-clinical research. Only the promising drugs can move forward for more research. Then the FDA must review and approve the Investigational New Drug Application (IND) for the clinical trials using humans. Many clinical trials to develop new interventions are conducted in phases and there are 3 main phases of clinical trials, namely Phase I, Phase II, and Phase III. Phase IV trials are done after a drug has been licensed. As clinical trials progress, new drugs may move to later phases of testing where the number of participants increases to gather more information about the efficacy and possible side effects.
Fig.1 Phase Stage of Clinical Trails (Brown, 2011)
Phase I Clinical Trial
Phase I clinical trial is the earliest mandatory phase of a clinical trial in humans, which is done to determine whether a new biomedical intervention is safe and effective. In this phase, a clinical trial is conducted in a very small number of healthy volunteers (e.g., 20-100). The contents of Phase I trials normally include the identification of safe dosage range and side effects. Safety is the main concern and the researchers need to see that the new treatment is safe and effective in patients. In addition to evaluating the safety and ideal dosage, researchers also look at the best administration route. If all goes well in this phase, the treatment can move on to the next stage. According to the FDA, approximately 70% of medications move on to phase II.
Phase II Clinical Trial
This next phase of the trial usually includes a larger group of participants (several hundred) and can last as long as 2 years. The purpose of Phase II clinical trial is to learn more about the side effects of the treatment and further assess its effectiveness. In this phase, patients with the same type of cancer get the new treatment using the dose and method found to be the safest and most effective in phase I studies. Everyone gets the same dose in phase II clinical trials and Placebos (inactive treatments) are not used in phase II trials. The less common side effects may be seen in phase II trials due to the larger numbers of patients. If the studied drug proves to be effective, and the side effects aren’t too bad, then it will move to Phase III. Usually, about 33% of drugs entering Phase II trials progress to the next phase.
Phase III Clinical Trial
Phase III studies are done to further evaluate the drug’s effectiveness, safety, and side effects in around 300-3,000 study participants and can last 1-4 years. During these trials, the investigational drug is compared with other standard or experimental interventions. The participants are often picked at random to get either the new treatment or the standard treatment, and even neither the patient nor the doctor knows which of the treatment is getting (called a double-blind study). Phase III clinical trials are often done in many places across the country at the same time, and Placebo may be used during this phase. As with other trials, the side effects of the new treatments are watched closely. Approximately 25-30% of drugs in Phase III studies will move to the next phase or approval per the FDA.
Phase IV Clinical Trial
Phase IV studies are done after a drug is already FDA approved and has been marketed. The goal of these studies is designed to monitor the effectiveness of new drugs and to collect information about any adverse effects. Even after testing in Phase I, Phase II, and Phase III studies, all the effects of the treatment may not be known. Therefore, the approved drugs need to be watched over a long period. Phase IV studies look at long-term safety, which allows researchers to determine how well this newly approved drug works over a long period and possibly identify side effects not detected in the earlier stages. In addition, they can be used to study the potential use of new drugs in different situations or combination with other therapies. Phase IV studies may also look at other aspects of the treatment, such as quality of life or cost-effectiveness.
Brown, S., Gregory, W., Twelves, C., Buyse, M., Collinson, F., Parmar, M., Seymour, M. and Brown, J., 2011. Designing phase II trials in cancer: a systematic review and guidance. British Journal of Cancer, 105(2), pp.194-199.