A Guide to Understanding Clinical Trials: Part 1 - What They Are and How They Work

A Guide to Understanding Clinical Trials: Part 1 – What They Are and How They Work

By Gloria Rosado | Clinical Care Research, COVID-19, Infectious Disease, Medicine | 1 comment | 3 June, 2020 | 0

When a new disease such as COVID-19 is discovered, it is up to doctors and scientists to investigate how the disease behaves so treatments can be developed and tested.
There are numerous clinical trials for COVID-19 therapeutics across the globe, and results from these trials (often uncontrolled and published in non-peer reviewed journals) are being released on a regular basis.

With all of the new information coming out so rapidly, it can be confusing to understand what these results mean. The Mass General Research Institute is providing a resource to explain how clinical trials work and share what makes for a strong clinical trial with clear and promising results.

What are clinical trials and why are they important?

Clinical trials are scientific studies designed to test the safety and usefulness of new medical interventions such as treatments, devices, preventative care, screening or diagnostic procedures, and more.

They are crucial to the advancement of strong science and patient care because, if well-designed, they can validate the performance of an intervention under controlled circumstances to ensure it is safe, effective and provides measurable benefits to patients.

How do they work?

Scientists typically conduct research on a disease or potential treatment for several years to lay a foundation for a clinical trial. During this time, they are gathering as much information as possible to learn about how a disease behaves, what it does to the body, which populations are at risk for it and what may be potential targets for treatment. Research can move into the next phase, called preclinical or translational research, once enough promising and validated reproducible data have been generated to justify further testing.

Preclinical trials are the first opportunity to see how a treatment may work in specific non-human models. In this stage, scientists must follow strict guidelines to test their interventions in vitro (in a petri dish or test tube) or in vivo (in a living organism such as an animal model) before moving on to human trials. If the findings are promising, investigators must fill out the necessary paperwork and get approval so the study can move onto a Phase I clinical trial.

What happens in the four phases of clinical trials?

According to the Federal Drug Administration (FDA), there are four phases of clinical trials that each inform decisions made in the next phase:

Phase 1

Focus: Establishing the safety and correct dosage of a treatment
Time frame: Typically lasts several months
Sample size: 20-100 participants who are either healthy or have the targeted condition
Bottom line: Designed to understand how the treatment and dosage are tolerated within the human body

Phase II

Focus: Investigating the efficacy and side effects of a treatment in patients with the disease
Time frame: Typically lasts several months to two years
Sample size: Several hundred participants with the targeted condition (not large enough to show whether a treatment will be beneficial)
Bottom line: Provides scientists with both efficacy and safety data, which can help refine research questions and inform study protocol for Phase III

Phase III

Focus: Further investigation into efficacy and monitoring of adverse side effects
Time frame: Can last anywhere from one to four years
Sample size: 300 to 3,000 participants
Bottom line: The larger sample size and longer study duration provides more information on long-term or rare side effects. After phase III, data is submitted to health authorities and the FDA considers the treatment’s approval and marketing.

Phase IV

Focus: Assess the cost-effectiveness and performance of a treatment in real-life scenarios after the treatment has been approved by the FDA
Time frame: Several years
Sample size: Several thousand participants
Bottom line: Since the treatment has been approved and marketed to the general public, Phase IV trials allow for the continued performance and safety monitoring in a broad population over an extended period of time.

How have clinical trials for COVID-19 been moving so quickly?

In the interest of time for COVID-19, instead of searching for a new treatment, scientists have opted to test treatments that have already been approved for other diseases or have been tested in humans. Some of the first medications to be tested were remdesivir and hydroxychloroquine, two antiviral medications that were developed for Ebola and malaria, respectively.

By starting with a treatment that has been tested extensively in humans, researchers can take advantage of the years of research, preclinical trials and early phase safety trials that have already been conducted on these drugs to move quickly into human patients.
While the results from these early clinical trials have generated lots of media attention and it’s understandable that people are eager for good news—it’s important to look past the headlines and into the details of the trial itself.

COVID-19 Research at Mass General
Researchers and clinicians at Massachusetts General Hospital Research Institute are mobilizing to develop new strategies to diagnose, treat and prevent COVID-19. Learn more.

Charlotte Fleet Reply May 25, 2022 at 6:49 pm

I loved learning that clinical trials help to test the safety of new medical treatments or devices. I think it would be smart to find a clinical research company that has a lot of experience. Along with that, it’d be smart to find one that works with a health condition you are familiar with.