From cancer treatments to game-changing therapies for autoimmune disease, medicines and medical devices need to be tested and approved by the FDA before they can be widely used. In the time of COVID-19 — when vaccines hold a key to moving life toward normal — we’ve seen headlines about various vaccines being tested in clinical trials and approved for emergency use by the FDA.

Our institute has conducted clinical research for decades, working closely with Virginia Mason to shape new therapies. BRI scientists are involved in many types of clinical research that studies whether new preventions and treatments— including the Pfizer vaccine for COVID-19 — appear safe and effective. We recently asked members of BRI’s clinical research program common questions about this type of research. They shared insight on how vaccines and medicines are tested before they are widely available.

What is the purpose of a clinical trial?

A clinical trial is a research study to answer specific questions about vaccines, new therapies or new ways to use existing medicines. Clinical trials are used to determine whether new drugs or treatments may be safe and effective.

How do clinical trials work?

Developing and testing vaccines, medicines and devices starts with an idea about a new approach for treatments. The idea then gets tested in the laboratory. The stages before clinical trials start include:

• The exploratory stage. This stage is when scientists explore different approaches to creating vaccines or treatments in the lab. With a COVID-19 vaccine for example, they may study different ways to get the body to fight off the virus.
• The preclinical stage. Once they have an idea for a vaccine or treatment, scientists do many more laboratory tests to demonstrate reasonable proof that the approach may work in the lab. This includes examining the makeup of a drug or vaccine to make sure it's exactly how they envisioned it. They use models to understand if and how the product would have the desired effect (say, preventing coronavirus infections).

We learned that multiple COVID-19 vaccines were over 90 percent effective in efficacy studies.

What does that mean? What are the phases of clinical trials?

If preclinical tests are successful, vaccines will move into the clinical development process, where scientists study if a medicine or device may be safe and effective in people. Efficacy studies investigate if a therapy is effective – if it has the desired result under typical circumstances. This largely happens during the second and third phases of clinical trials. The phases of clinical trials include:

• Phase 1: A small group of people (20-100 for the Pfizer vaccine) receive the vaccine or treatment. The goals are to make sure the medicine or device doesn’t cause serious medical problems and to gather initial evidence about effectiveness – meaning that it could prevent or treat the disease.
• Phase 2: More people (as many as several hundred) receive the medicine or treatment being tested. During this phase, researchers further study its possible effectiveness, and look at things like finding the right dose and better understanding any risks and side effects. If researchers determine that it appears safe and could be effective, they may then expand the study to a larger group of people.
• Phase 3:  Even more people get the vaccine or treatment. The Pfizer vaccine trial involved more than 40,000 people. Scientists continue to evaluate it for safety (understanding potential risks and side effects) and efficacy (how well it works).

Phase 1 of trials typically takes a few months to a year, while Phases 2 and 3 usually take a year or more. Because of the urgency of COVID-19, scientists around the world (like many at BRI) have pivoted their work to study the virus — and funders have put forward large sums of money to help find answers. This global research effort has enabled vaccine research to progress faster than ever before.

“Researchers look at the data from a Phase 3 trial to see whether the intervention is effective — for example, if a vaccine prevents COVID-19 infections,” says Cecilia Morgan, PhD, BRI’s director of clinical research operations. “Data is also reviewed by the FDA — and if they approve, it can be licensed and distributed to the public.”

Depending on the type of trial, best practices also include:

Placebo-controlled and randomized

When a study is placebo-controlled, one group gets the experimental prevention or treatment and the other gets a placebo (a medicine or treatment that doesn’t have any effect on the body). This helps researchers better understand whether the prevention or treatment they’re studying works and to understand its safety, by directly comparing people who got the treatment and who didn’t.

Who gets the placebo and who gets the treatment is determined by randomization. Participants are randomly assigned into two or more groups. For example, randomly assigned to experimental (receiving the prevention or treatment) and control (not receiving the experimental prevention or treatment). By using a computerized tool or other way to randomly divide people into groups, researchers can be more certain that the differences seen between the groups are a result of whether or not they received the treatment, and not a result of other characteristics of people who may be in each group.  

Blinded/double-blinded or Masked/double-masked

In a blinded or masked study, participants don’t know if they got the prevention/treatment or the control (placebo). This helps limit bias in a study (for example, if a participant knew they got the treatment, they may think they feel better, even if their symptoms haven’t changed).

In a double-blinded/double-masked study, neither the participants nor the research team know who received the prevention or treatment and who received the control. This also helps researchers ensure that the therapy, and not other factors, lead to a certain outcome. However, sometimes blinding/masking researchers isn’t possible because of how the therapy is administered or because certain therapies require specific safety measures in the lab.

Who can participate in clinical research?

Clinical trial research participants should include the people who are most likely to benefit from that drug, vaccine or device. This helps researchers evaluate whether the product appears safe and effective for everyone who needs it. 

“With COVID-19, for example, data shows that the virus impacts older people and people of color more severely,” Dr. Morgan says. “If a COVID-19 vaccine was only tested in groups that don’t include those demographics, you wouldn’t know if it would work for those groups.”

Research participants must meet certain criteria — which may include age, gender and health information — to be eligible for a clinical trial. BRI has many types of clinical studies, ranging from testing new therapies for autoimmune diseases to studies gathering data from largely healthy people. For example, the Sound Life Project is collecting health data over time from people who don’t have diseases of the immune system to help inform treatments for immune system disease. 

“Our studies encompass many different groups, we’re always looking for new research participants — and we are very grateful to those who participate in our trials!” Dr. Morgan says.