Clinical trials are divided into several phases, and each phase can be thought of as its own study. It may take many years for a treatment to pass through the various phases.
Preclinical testing in model systems, such as animal models, is usually conducted before clinical trials involving humans. The phases of human testing are:
- Phase 0 – Study how the drug interacts with the disease tissue and affects the body in a small number of subjects.
- Phase I – Determine the safety of the treatment and the most appropriate dosage (of a medication) that can be safely given. Although it is possible that some benefits may be realized from Phase I treatment, this is not the primary aim of the study.
- Phase II – Determine the efficacy of the treatment. Specific criteria are established in advance to judge whether the treatment is working; side effects are also monitored.
- Phase III – Compare the efficacy of the treatment to other existing treatments for the disease.
- Phase IV – Monitor the treatment after FDA approval for long-term outcomes and rare side effects.
Following completion of Phase III, clinical trial data may be submitted to the FDA for approval, generally for indications that were tested in the clinical trial.
For rare diseases, however, it is possible that Phase II data may need to be submitted, for two reasons. First, there may not be enough affected individuals to do a complete Phase III study for a rare condition. Second, for rare diseases, there may not be a known effective treatment to compare with a new treatment.
N of 1 Trials
As more is learned about the cause of specific rare diseases, it sometimes is possible to implement a treatment that has never been tested before and where it is not possible to organize a randomized clinical trial with a large number of participants.
In special circumstances, it might be possible to conduct a trial just in a single patient, comparing symptoms with and without treatment. If it is an existing FDA-approved drug, it may be used clinically, as described above, as an off-label use. If it is a new drug, special FDA approval must be obtained to test it in a patient.
