Clinical research has been conducted throughout human history, beginning with the ancient civilizations who performed medical observations to identify the best use of herbs and drugs. However, it wasn’t until the early 20th century that scientists developed regulations for a “well-controlled” therapeutic drug trial.
The FDA was enacted in 1938 to evaluate the safety of new drugs, and the 1962 Drug Amendments introduced requirements for the FDA to base approvals on scientific testing and evidence. Today, in the 21st century, clinical researchers use a meticulous and highly controlled medical trial process to evaluate the effects of an intervention on health outcomes. This process involves four phases, each with a specific purpose.
A Phase I clinical trial begins after extensive laboratory research on a certain drug or device. Testing using animal and human cells may take months or years before the research is sent to the FDA for approval to continue research and testing using human volunteers.
The goal of Phase I is to evaluate the safety of the drug or device. Only a small number of participants, usually less than 100 healthy volunteers, partake in this phase of the clinical trial. Overall, researchers design Phase I to identify how the drug is absorbed, metabolized, and excreted.
By giving increasingly larger dosages to healthy participants, researchers are able to learn more about the drug’s behavior and observe common side effects. About 70% of all clinical trials pass Phase I and receive FDA approval to move into Phase II.
During Phase II trials, the same drug or treatment is given to a larger group of people, usually up to 300 participants. Instead of focusing only on safety, Phase II trials gather data on the drug’s efficacy.
Due to the need for objective data and the involvement of additional volunteers, Phase II trials are randomized. This means that one group of patients receives the experimental drug while a second group serves as the “control”. The control group either receives a standard approved treatment or a placebo in order to establish a baseline for comparison to the experimental drug.
In addition to being randomized, Phase II trials are often “blinded” as well. This means the researchers and patients are not informed of who is placed into the experimental and control groups. This ensures that all data is objective, not tainted by expectations or theories. Only about 30% of all clinical trials pass Phase I and Phase II for approval of Phase III.
A Phase III trial is much larger than the phases before it. Most Phase III trials enroll thousands of volunteers to collect, confirm, and assess the following information about the experimental treatment:
- Side effects
- Performance compared to current treatments
- Safety factors
Due to their size and scope, Phase III trials may last for years. Upon successful completion, a pharmaceutical company requests approval from the FDA. The FDA reviews the results of the study and determines whether it should be approved for marketing and consumer use.
All Phase III clinical trials approved by the FDA then enter Phase IV. This phase doesn’t involve the use of additional volunteers. Instead, it serves a few specific objectives:
- Compare the approved drug with other drugs on the market
- Monitor the drug’s long-term benefits and side effects
- Establish the drug’s cost-efficiency compared to other treatments and therapies
Depending on the results of Phase IV, a treatment may be restricted, taken off the market, or approved for long-term use.