Recognizing the Importance and Complexity of Clinical Trials
Researchers and reviewers spend months or even years addressing the complexity of clinical research. They look at each study carefully to ensure the procedure is as effective as possible and the results will further our knowledge of diseases.
To learn about the effectiveness and safety of new medical treatments, scientists must conduct clinical trials that look at how these treatments work in actual patients.
The complexity of clinical research is staggering. Whether you've thought about participating in a study or want to know more about how drug studies work, here's an inside look.
How Do Drugs Get to Clinical Trials?
The research process starts long before a drug enters clinical trials. Researchers use prior studies and laboratory experiments to investigate scientific questions, such as how certain cancers develop.
If a study team thinks it has an idea for a new therapy, the scientists start researching details such as dosage. Research begins in the lab with cell samples and animal experiments.
Studies that show promise at this phase may move into clinical trials. However, before that happens, the study team must develop a research plan called a protocol.
The protocol must earn approval from the U.S. Food and Drug Administration (FDA) and the university sponsoring the research. Reviewers must ensure the trial is scientifically valid and safe for human volunteers.
Phases of Clinical Trials
Before clinical trials in humans can commence, an Investigational New Drug (IND) application must be submitted to the U.S. Food and Drug Administration (FDA). This application is an important step that provides comprehensive data on the drug’s preclinical studies, including animal testing results and safety profiles. The IND application also outlines the proposed plan for clinical trials, detailing the protocols for phases I, II, and III and ensuring that the rights and safety of human participants are protected. The FDA reviews this information to determine whether the investigational drug is reasonably safe to proceed to human trials. This regulatory step is essential to ensure that any potential risks are minimized and that the proposed trials are scientifically sound and ethically conducted.
Once a study has received approval, researchers can start investigating the drug using human volunteers. There are four phases of clinical research, and each study must complete one stage before going on to the next.
Phase I
Scientists use Phase I trials to investigate different doses. Phase I trials usually involve:
- Treatment mechanism trials: Explore how a treatment works in the body, focusing on the biological processes it affects to improve and optimize the treatment.
- Dose-finding trials: Determining how much of the drug the body can tolerate or how little the doctor can administer to have the desired effect. These are called maximum tolerable doses and minimum effective doses, respectively.
Phase I trials typically involve 20 to 80 volunteers — a small number considering the thousands of patients involved in later tests. In some cases, researchers may investigate dosage safety using volunteers who don't have the studied disease.
Phase II
Phase II trials seek more information about the treatment's effectiveness and safety. A Phase II study is often the first time someone with the disease in question will receive the drug or procedure.
Phase II trials typically need 100 to 300 volunteers. More patients provide more data about benefits and adverse effects.
For example, a drug could be promising if 5 out of 20 patients benefit. However, if 5 out of 300 patients benefit, the effectiveness is more questionable.
At the end of Phase II, the FDA and the pharmaceutical company will meet to decide whether the treatment is effective and safe enough to progress to Phase III.
Phase III
A Phase III trial studies the effects of a treatment on a large group of patients—typically 1,000 to 3,000 people across multiple locations. However, the number may be higher depending on the study. For example, the Phase III clinical trial for one COVID-19 mRNA vaccine recruited more than 43,500 volunteers.
Phase III trials compare the effectiveness of a drug against standard or no treatments. Scientists accomplish this goal by sorting volunteers into two groups—a control group and a treatment group. This step is called randomization. The treatment group receives the studied therapy. The control group receives a placebo—an inactive substance that has no effect but looks and feels like the studied drug.
Most studies are blinded, meaning patients don't know whether they receive the placebo or the studied treatment. Sometimes, even the researchers don't know who received which treatment until the study is over. This is called a double-blind study, and it helps to reduce bias and ensure patients report what happens, not what they think will happen because they're taking a particular drug.
If the tested treatment is safe and significantly effective, drugmakers can apply for approval from the FDA. The drug must have authorization before the company makes it available to the public.
Phase IV
Drug companies use Phase IV trials to study new therapies in their post-approval phase. One reason for doing this is to study rare outcomes or adverse reactions that may not appear in studies with a few thousand patients. By studying a drug in widespread use, researchers can learn more about how it performs in a wider variety of patients.
Phase IV trials also allow scientists to integrate the new drug into treatment plans. For example, in cancer research, oncologists use Phase IV trials to test the effectiveness of new therapies in conjunction with surgery or other established treatments.
What Makes a High-Quality Clinical Trial?
You can learn the most about clinical research complexity by looking at the rules of trial design. Scientists must make a clinical trial as reliable and trustworthy as possible. They do this by:
- Identifying a specific study question and the steps needed to answer that question
- Reducing variables that could influence results — for example, using the same lab for all testing to ensure a consistent procedure
- Choosing participants who accurately represent the patient population
- Increasing objectivity through randomizing and blinding
Researchers and reviewers spend months or even years addressing complexity in clinical research. They look at each study carefully to ensure the procedure is as effective as possible and the results will further our knowledge of diseases.
Who Can Participate in Clinical Trials?
Each trial—and each trial phase—has different participation needs. For example, a Phase I study may need healthy adults from as many ethnic groups as possible so safety data is complete and accurate. When the same drug moves to Phase II or III, the researchers may decide to narrow the age range or include patients with a specific medical profile.
Scientists need to study new therapies on diverse populations, but volunteer statistics don't always reflect that goal. For example, a recent study showed that vaccine clinical trials recruited more working-age adult females and fewer racial and ethnic minorities and older adults than the general population. Historically underrepresented volunteer populations are precious to vaccine and treatment researchers because they show how the studied drug will affect diverse communities.
At Studypages, we're committed to helping research teams find the volunteers they need to move science forward. If you're curious about participating, check out studies that may be recruiting in your area. To stay connected to the latest health and research news, Sign up for our free Pulse newsletter today!