New medicines are developed through a series of controlled trials which assess the safety and efficacy of each new medicine by applying high scientific standards. 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 trials involve volunteer trial participants. To ensure that such trials are conducted ethically, there are extensive rules and standards governing the trial design; investigator qualifications and training; external review by regulatory bodies or institutional boards; ongoing monitoring of all of the trial sites; and obtaining informed consent after the presentation to the potential trial participant of the risks and potential benefits of participation. All trial participants are free to withdraw from the trial at any time.
The Phases of Clinical Development
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 tolerability, 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, although for some medicines, the first trials in human participants are 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 the investigator to measure the participant's clinical response to the medicine, whether the medicine is sufficiently absorbed, how long the medicine remains in the bloodstream after dosing, and which dosage levels are safe and well tolerated.
In Phase 2, the focus of the trials is on the effectiveness of an experimental medicine in treating an illness or medical condition. Information about the experimental medicine's safety, side effects, and potential risks are 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 (e.g., tablets, extended release capsules, infusions, injections, etc.). Phase 2 clinical trials involve a larger number of trial participants; typically up to several hundred participants (although in some cases there could be fewer than 100). The participants studied in 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 centers, clinics, and hospitals at multiple sites around the world.
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 (sugar pill) or another medicine (a "comparator"). Phase 3 trials generally provide the primary basis for the benefit-risk assessment for the new medicine and much of the core information about the medicine that is analyzed for inclusion that will be described in the labeling of the medicine.
The next step in bringing a 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 the U.S., a New Drug Application (NDA) is filed with the U.S. Food and Drug Administration (FDA), and in Hong Kong, registration filed with Department of Health is necessary. 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 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.