Have you ever wondered why new drugs that you see reported in the papers never seem to become available, or if they do, it’s many years down the line? Drug approval is a long and expensive process, and in this article I intend to explain the process referred to as ‘clinical trials’ which determines whether a new drug will become a medicine that your doctor prescribes.
Clinical trials are studies that use human volunteers to test the safety and efficacy (i.e., effectiveness) of potential treatments. In order for these new treatments to be approved, they must go through several stages or phases of testing.
Before studies can be conducted on human subjects, the potential treatment (investigational product) must go through pre-clinical development, which involves testing both in vitro (testing on cells in flasks) and in vivo (testing in animals such as mice) to observe its toxicity and estimate a safe starting dose for humans.
Once the investigational product passes pre-clinical development, the next step is testing on human subjects. Phase 0 trials are the first trials involving human subjects. In these trials, a small number of healthy human subjects (around 10-20 subjects) are exposed to small doses of the investigational product to determine pharmacokinetics (what the body does to the investigational product) and pharmacodynamics (what the investigational product does to the body). Only ten percent of drugs that enter Phase 0 go on to be approved by the Food & Drug Administration (FDA) in the United States.
The next phase in clinical trials is Phase I. In this phase, healthy human subjects (around 20-80 subjects) are exposed to various doses of the investigational product to determine safe dose ranges and observe any side effects.
If the investigational product is found to be safe in Phase I, testing in Phase II trials can begin. This phase involves testing the investigational product on a group of subjects (around 100-300) with a specific disease or indication to determine the efficacy compared to a placebo or different drug, and to further assess its safety.
After Phase II trials, larger scale trials will be conducted to confirm the safety and efficacy of the investigational product. In Phase III trials, a large group of subjects (around 1,000-3,000) with a specific disease or indication will be randomly selected (randomized) to receive either the investigational product, placebo, or current/commonly used treatments. The results from the group (treatment arm) that received the investigational product will be compared to the treatment arms that received the placebo or other treatment to determine if the investigational product is as effective as treatment already available.
For example, Pfizer announced in November 2016 that it will discontinue trials of their investigational cholesterol-lowering medication, bococizumab, which was in Phase III of clinical development, due to an increase in adverse reactions compared to PCSK9 inhibitors already on the market.
If the investigational product is found to be safe and effective, it can then be approved to be marketed and sold. The investigational product will also undergo Phase IV trials, in which subjects are monitored for any adverse events/reactions while the drug is on the market.