New prescription medicines are developed through a series of carefully controlled phases, which help to best determine the safety and efficacy of each new medicine by applying the highest scientific standards.
After extensive preclinical testing of an experimental medicine, clinical studies are conducted in volunteer study subjects across all phases of medicine development. To ensure that such studies are ethically conducted, careful attention is paid to the study design; investigator training; external Institutional Review Board (IRB) or ethics committee review; monitoring of study sites; and accurate presentation to potential study subjects of the risks and potential benefits of participation through the informed consent process. The participant confirms his or her willingness to take part in a study with a written, signed document called the informed consent. Informed consent is not a contract, and participants are free to withdraw from the trial at any time.
The Phases of Clinical Development
Phase I
In Phase I clinical trials, a prospective medicine, also called an "investigational new drug", is studied for the first time in human subjects. Phase I 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 subjects under the close supervision of an investigator. Study subjects are typically healthy individuals, although for some types of medicines, Phase I trials may be conducted in patients who have the condition that the experimental medicine is intended to treat. The dose of the new medicine is gradually increased to allow the investigator to measure the 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.
Phase II
In Phase II clinical trials, the focus is on the experimental medicine's effectiveness against an illness or medical condition as well as its safety, side effects, and potential risks. During Phase II, researchers also seek 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.). This stage involves a larger number of study subjects; typically up to several hundred (although in some cases there could be fewer than 100). The subjects studied in Phase II are usually patients who have the medical condition that the experimental medicine is intended to treat, and who may be recruited by physicians at research centers, clinics, and hospitals around the world.
Phase III
Phase III clinical trials are typically conducted in a larger population in order to confirm the results of earlier studies and gather additional information about the effectiveness and safety of an experimental medicine. This phase will usually involve several hundred to several thousand subjects from multiple sites with many different physician-investigators. These trials are often randomized and "double-blinded." "Double blinded" means that during the study, neither the investigator nor the subject know whether the subject is receiving the study medicine, or a placebo (sugar pill), or a comparator medicine. Phase III studies 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 in the medicine's labeling.
Registration
The next step in bringing a new medicine to the 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 US a New Drug Application (NDA) is filed with the U.S. Food and Drug Administration (FDA).
In Europe, a Market Authorization Application (MAA) is filed with the European Agency for the Evaluation of Medicinal Products (EMEA). A description of the medicine's manufacturing process along with all quality data and study 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 made commercially available to patients.
Recent Approvals
Medicines that have recently been approved for marketing in the U.S. or Europe and are either currently marketed and available to patients or about to be launched and made available in the near future are known as "recent approvals."
Phase IV
Phase IV studies – also called "post marketing studies" – are conducted after approval of a medicine for marketing. Through such studies, researchers can collect additional information about long-term risks, benefits, and optimal use. These studies often involve thousands of subjects and may continue for many years.