Clinical Studies & Trials
For a drug to become a medicine that doctors can prescribe, investigational drugs must first go through testing in people. During drug development, most drugs are tested in steps or phases.
Each phase of a clinical trial helps researchers learn:
- How the drug works
- How much of the drug to give
- How often to take the drug
- Whether the drug is both safe and effective
Phase 1 Clinical Trials
After animal testing is complete, investigational drugs start the first phase of clinical trials. Phase 1 clinical trials are often held in a small group of healthy volunteers to assess whether the drug is safe and whether there are any unwanted side effects. In rare diseases like FOP, sometimes Phase 1 trials are conducted in people who have the disease.
Phase 2 Clinical Trials
If Phase 1 trials show an acceptable
, investigational drugs then move on to Phase 2. Phase 2 trials usually enroll a slightly larger number of individuals than Phase 1 and include patients who have the disease. Phase 2 trials involve additional testing of a drug’s safety and begin to test the medicine’s effectiveness (e.g. whether the medicine has a positive effect on the disease). Different amounts of a drug are often given during the trial to assess how much of the drug is needed to achieve its desired effect. Some Phase 2 trials have a group of participants taking a placebo to prove the effectiveness of the drug. A placebo can be a pill, a powder, or a solution that resembles the test drug, but has no treatment value.
In rare disease drug development, study medications that show substantial benefit may be approved on the basis of Phase 2 data alone.
Phase 3 Clinical Trials
During Phase 3 trials (sometimes referred to as “pivotal trials”), sponsors look to learn more about how people react to the drug. They watch for any side effects and attempt to confirm the effectiveness of the drug that was observed during the Phase 2 trial. Phase 3 clinical trials enroll a larger number of individuals with the disease than the Phase 2 trial, and often, the investigational drug is compared to a placebo to assess the medicine’s true effectiveness. In rare diseases, data from natural history studies may be used in comparison instead of a placebo.
In rare diseases, study sponsors sometimes combine phases. It’s not uncommon to see Phase 1 and Phase 2 trials combined or to have Phase 2 and Phase 3 trials combined. By combining trial phases, drug manufacturers hope to speed up the development timelines for new drugs.
Phase 4 Clinical Trials
After a drug is approved by the regulators (e.g. U.S. Food & Drug Administration, European Medicines Agency, etc), there may still be unanswered questions about the drug’s effectiveness or safety profile. Consequently, Phase 4 studies may be conducted to answer these questions, even after a medicine has been approved by a regulator and is available by prescription.
Natural History Studies
Natural history studies are a type of observational study that are designed to look at the course of a disease without any type of treatment or intervention (other than the standard of care). Natural history studies help researchers better understand the course of the disease over time and what demographic, genetic or environmental factors are associated with the disease progression.
A visual overview of how a drug moves through clinical trials:
Learn more about Participating in Clinical Trials.
