The US Food and Drug Administration (FDA) regulates a number of consumer products, including drugs, medical devices, vaccines, blood products, biologic agents, animal and veterinary products, cosmetics, tobacco products, radiation-emitting products, and food.
The FDA approved or added new indications to 47 drugs or biologics for oncology in 2018, and 20 such approvals in oncology have already been made in 2019.1 The drug-development process that may ultimately result in FDA approval is long and requires many steps to ensure that the product is safe and effective.
Although there are different regulatory paths for different types of products, most oncology drugs follow a similar overarching drug development path. The traditional drug development pathway can take up to approximately 15 years, but efforts have been made by industry and the FDA to reduce this timeline.2
Generally, drug development is a long process because a potential new drug must be identified and then evaluated in preclinical and clinical studies. The discovery of a potential new drug can occur several different ways.3 Researchers may identify a new drug by testing numerous compounds in a laboratory panel to assess for any beneficial effects, such as stopping cancer cell growth or killing cancer cells.
Sometimes, new understanding of a cancer type can lead to rational drug design, in which a compound is developed to target a specific disease process. Sometimes, existing drugs are found to have a beneficial effect against a different cancer type. Finally, new technologies and/or formulation designs can change how drugs reach cancer cells within the body, thus leading to the ability to develop a compound that may not have been possible previously. This initial process is referred to as target and lead identification, validation, and optimization.1
After initial testing, any promising compounds undergo further study in the laboratory.2,3 Preclinical studies are conducted using cancer cells and animals to determine how the compound is best administered and at what dose, its mechanisms of action, how the body absorbs and metabolizes the compound, how it interacts with other drugs, and its effectiveness compared with established drugs.3 Animal studies are often used to determine detailed information about dosing and toxicity.4
If the results from preclinical studies warrant in-human studies, the lead compound enters clinical testing.2 This process includes several stages of clinical trials: phase 1, phase 2, phase 3, and sometimes, phase 4 (which may also be referred to as the postmarketing or postapproval phase). Clinical studies are carefully designed to answer specific research questions about the compound for a specific indication.5
Phase 1 studies are small, and typically include approximately 20 to 100 healthy volunteers or patients with the target cancer of interest. The purpose of phase 1 is to identify a safe dosage, although the effectiveness of the compound is sometimes also assessed.
Approximately 70% of drugs that enter phase 1 clinical trials move on to phase 2.5 In phase 2 trials, the compound is tested in several hundred patients with the cancer type to evaluate any efficacy and adverse events.
Phase 2 studies can last from several months to up to 2 years, and usually do not have a control or placebo group. Approximately one-third of drugs that enter phase 2 will continue on to phase 3.5
Phase 3 clinical trials are larger can last for several years, and may include several hundred to several thousand patients with a particular cancer type. The purpose of phase 3 trials is to evaluate the safety and efficacy of the drug in a larger group of people, and these trials are typically used in the FDA application process.
Phase 3 trials are historically understood to be “pivotal” trials because they offer clinical support in a drug manufacturer’s quest to gain marketing application approval from the FDA; they are efficacy trials used as evidence to support the approval of a drug indication. Although confirmation of benefit is usually required in these trials, in oncology, drugs can be approved by the agency after a single pivotal trial.
If approved by the FDA, some drugs will go on to phase 4 testing. In this postmarketing setting, the long-term effects of a product are tracked.