How Trials Work
The phases of clinical development
New medicines are developed through a series of controlled trials which stringently assess the safety and efficacy of each new medicine. An experimental medicine is first tested in the laboratory and in animal studies. After this preclinical testing, the medicine can advance to clinical testing.
Clinical testing is conducted in clinical trials from Phase 1 to 4. A clinical trial is a biomedical or health-related research study in human beings that followed a pre-defined protocol.
Phase 1
In Phase 1, an experimental medicine, also called an ‘investigational new drug’, is administered, for the first time, to humans. Phase 1 clinical trials usually focus on safety and side effects, rather than the effectiveness of a new medicine. During this phase, low doses of an experimental medicine are administered to a small number of participants under the close supervision of an investigator. Trial participants are typically healthy individuals. However, for some medicines, the first trials are conducted on patients with the disease that the experimental medicine is intended to treat. The dose of the new medicine is gradually increased during Phase 1 clinical trials to allow investigators to measure the participant’s clinical response to the medicine, whether the medicine is sufficiently absorbed, how long the medicine remains in the blood stream after dosing, and which dosage levels are safe and well tolerated.
Phase 2
In Phase 2, the focus of the trials is on the effectiveness of an experimental medicine in treating an illness or medical condition. Investigators also collect information about the experimental medicine’s safety, side effects, and potential risks is also collected.
In this phase, researchers work to determine the most effective dosages for the experimental medicine and the most appropriate method of delivering it. Phase 2 clinical trials involve a larger number of trial participants, typically up to several hundred participants. The participants studied on Phase 2 clinical trials are usually patients who have the medical condition that the experimental medicine is intended to treat. They are usually identified by physicians at research centres, clinics, and hospitals at multiple sites around the world.
Phase 3
Phase 3 trials test the results of earlier trials in larger populations and gather additional information about the effectiveness and safety of an experimental medicine. This phase will usually involve several hundred to several thousand participants from multiple sites with many physician-investigators. These trials are often randomized and “double-blinded”. “Double blinded’ means that during the trial, neither the investigator nor the participant know who in the trial are getting the experimental medicine versus a placebo (medicine look-alike with no active ingredient) or another medicine (a “comparator”) in order to avoid bias when assessing treatment outcomes.
Registration
The next step in bringing new medicine to market is the filing of an application with the health regulatory authority of a country in order to obtain approval to market the new medicine. This step is known as registration. In Singapore, a Western Drug Product Licence is filed with the Health Sciences Authority. A description of the medicine’s manufacturing process along with quality data and trial results are provided to the health regulatory authorities in order to demonstrate the safety and effectiveness of the new medicine. If approval is granted, the new medicine can then be sold for use by patients.
Phase 4
Phase 4 trials – also called ‘post marketing studies’ – are conducted after the regulatory approval of a medicine. Through such trials, researchers collect additional information about long-term risks, benefits, and optimal use. These trials often involve thousands of subjects and may continue for many years.