By Jaimy Lee
Whether you’re new to investing in pharmaceutical or biotechnology companies or simply paying close attention to the race to develop a COVID-19 vaccine, questions may have occurred about how clinical trials work — here’s what you need to know to understand the process.
The first thing is that we’ve never seen vaccines developed as quickly as what is happening right now. It took a year and a half to develop a Zika vaccine, four years for a mumps vaccine, and 10 years for a flu vaccine.
The COVID-19 vaccines being developed by AstraZeneca /zigman2/quotes/200304487/composite AZN +1.46% /zigman2/quotes/203048482/delayed UK:AZN +0.13% and the University of Oxford, BioNTech /zigman2/quotes/214419716/composite BNTX -0.27% and Pfizer Inc. /zigman2/quotes/202877789/composite PFE -0.63% , and Moderna Inc. /zigman2/quotes/205619834/composite MRNA -1.05% are well into Phase 3 clinical trials in the U.S., with the makers of all three claiming it’s possible to have clinical data from the late-stage studies for their vaccine candidates during this calendar year.
It’s been nine months since Chinese authorities first notified world health officials about the presence of the virus.
What each clinical-trial phase means
Preclinical studies: These are studies that test how a drug or vaccine fares in animals, often macaques, a kind of monkey, or mice. These studies are traditionally performed before a therapy or vaccine moves into clinical trials with humans; however, in the pandemic, some preclinical trials for COVID-19 vaccines have been conducted concurrently with Phase 1 trials. “I don’t think proving this in an animal model is on the critical path to getting this to a clinical trial,” Dr. Tal Zaks, Moderna’s chief medical officer, told Stat News in March.
Phase 1 clinical trial: These are small studies designed to evaluate the safety and efficacy of a drug or vaccine in healthy adults. In the case of the COVID-19 vaccine candidates, this means fewer than 200 people were enrolled in the early-stage studies in the U.S., including ones conducted by BioNTech and Pfizer, Inovio Pharmaceuticals Inc. /zigman2/quotes/202993817/composite INO -1.96% , and Moderna Inc. Inovio’s early-stage study enrolled 40 people.
These trials focus on safety; assess immunogenicity, which is the ability to generate an immune response; and help researchers better understand the correct dosing amount. (Based on the Phase 1 findings, for example, BioNTech and Pfizer plan to advance a two-dose regimen of 30 micrograms of their candidate, BNT162b2, into the Phase 2/3 trial.)
Phase 2 clinical trial: The midstage studies also assess dosing amounts and enroll hundreds of participants. In some cases, the trials overlap, such as Novavax Inc.’s /zigman2/quotes/202614340/composite NVAX -2.65% Phase 1/2 study for its experimental COVID-19 vaccine, which has enrolled 131 healthy adults between the ages of 18 and 59. (The first two phases of the study are being conducted in Australia, but the late-stage trial is expected to be conducted in the U.S.) “This phase includes studies that may provide additional information on common short-term side effects and how the size of the dose relates to immune response,” the Food and Drug Administration has stated in public documents.
It’s common for phases to overlap, said Dr. Henry Miller, a former FDA official. “Phase 1 merges almost imperceptibly into Phase 2 very often,” he said.
Phase 3 clinical trial: This is the crucial phase. The goal is to enroll thousands of people, to better evaluate how a vaccine candidate performs in a significantly larger patient population. AstraZeneca, BioNTech, Pfizer and Moderna have all committed to enrolling up to 30,000 participants in their late-stage trials. “Phase 3 is the final and most important phase where the vaccine candidate is tested in the field, if you will,” said Dr. Howard Koh, professor of public health leadership at the Harvard T.H. Chan School of Public Health and a former U.S. health official.
Postmarketing surveillance: In short, this is a way to track the product’s effectiveness as well as any potential side effects once it is distributed in the real world. “Monitoring is essential for two reasons,” the FDA has said. “First, even large clinical trials may not be big enough to reveal side effects that do not happen very often. ... Second, vaccine trials may not include groups (including pregnant women or older adults) who might have different types of side effects or who might have a higher risk of side effects than the volunteers who got the vaccine during clinical trials.”
Other terms and distinction you should be aware of
What is an adverse event?
These are negative reactions or side effects to drugs or vaccines being tested. In vaccines, adverse events usually crop up within two months of dosing, according to Sept. 10 remarks by Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
An adverse event recently caused AstraZeneca to halt the Phase 3 study of its vaccine candidate, citing a “potentially unexplained illness” in one of the trial’s participants. According to RBC Capital Markets analyst Brian Abrahams, the participant in the study whose health triggered the hold reportedly was diagnosed with transverse myelitis, a rare spinal disorder potentially associated with vaccines. (AstraZeneca has not confirmed the type of illness, which was first reported by the New York Times .)