What are Clinical Trials?
Clinical trials are the last step in the development of new drugs.
Before new agents are tested in humans, they have been extensively investigated in the laboratory with different tests.
Only if this range of laboratory and animal tests show positive results, the drug can be tested in humans.
In a clinical trial, patients sign an informed consent and accept to participate in order to test a new drug or a new combination of new or existing drugs, a new surgical intervention or a new radiotherapy regimen. Other trials evaluate new screening methods, biomarkers or imaging techniques.
Without clinical trials, no new drugs, no new treatment regimens or no new biomarker or imaging test can be approved and thereafter routineously used in patients. Each treatment now in routine use previously went through this rigorous process of test in a clinical trial.
Phases in clinical trials
In phase I, a small group of patients is selected to evaluate the effects of a drug on the human body. The most important results in this phase are the safety profile and adverse events associated with the drug. In addition to this, investigators also try to define the correct dosage and evaluate antitumor activity.
If phase I shows that the drug is well tolerated and was able to identify the correct dosage, phase II is started. In this phase, a larger group of patients is selected in order to further analyze the effects and adverse events of the drug. Efficacy is also a major endpoint of phase 2 trials.
In phase III, the new drug is compared with the existing standard treatment (or placebo) in a very large patient population. These patients are divided into two (or more) groups of which one or more groups receive the new drug and one group is treated with the standard treatment (=standard of care). This division into treatment arms is done randomly. In many cases, patients and investigators don’t know if in addition to standard therapy they receive also the new drug (double blinded trial) By doing so, researchers avoid biaises. In this phase, the investigators analyze whether the efficacy and adverse events of the new treatment are comparable, better or worse compared to the standard treatment. Once an experimental treatment is associated with a better outcome in a phase III clinical trial, the sponsor can submit an application for official registration in this indication in order that the drug can become a new standard of care.
Phase III B or IV trials (postmarketing) are conducted to identify more rare side effects and to evaluate the long term effects of new drugs and treatments in a larger patient population. They are started after market approval of the drug. These trials are important in order to confirm market approval. According to the outcome market approval can be withdrawn.