As researchers race to develop a COVID-19 vaccine, associate professor Shobha Swaminathan, principal investigator at the Rutgers New Jersey Medical School Clinical Research Center and the medical director of Infectious Diseases Practice at University Hospital, and Michael K. Gusmano, a bioethicist and professor of health policy at the Rutgers School of Public Health, discuss how clinical trials work, the ethics of developing and distributing a vaccine, safety and efficacy in clinical trials and what a successful vaccine may mean.
Why is Rutgers involved in a vaccine clinical trial?
Swaminathan: It’s very important to include people from populations like our local community, which has been impacted by the COVID-19 pandemic, and suffered a higher incidence and more severe disease outcomes and needs access to vaccines that could protect them. The Rutgers New Jersey Medical School Clinical Research Center is one of over 90 clinical trial sites across the United States selected to participate in the Phase 3 Moderna COVID-19 vaccine trial. Our site has been funded by the National Institutes of Health and industry partners to conduct clinical trials for about 15 years – proudly serving local communities in the state of New Jersey while providing cutting edge research and engagement opportunities.
What are the general developmental processes in getting a COVID-19 vaccine ready for safe use? What do the different phases mean?
Swaminathan: A vaccine helps your immune system produce antibodies that can help fight and prevent infections. When researchers pursue a path to creating a new therapy, such as a vaccine, there are typically four phases to this voluntary research process.
The Moderna vaccine trial completed phase 1 of its study in July 2020 and has 600 participants enrolled in phase 2. Both remain under long-term safety follow-up.
Phase 3 marks the start of large-scale testing of participants of various ages and ethnic groups across the U.S. It is the final step needed to seek the Food and Drug Administration's approval to market the vaccine if it is found to be safe and effective.
In the phase 3 trial, some participants receive the active vaccine and others an inactive injection, and their experiences are compared. The fourth and final stage of research evaluates the long-term effects of the vaccine and its impact on other special populations such as children. The results of the Moderna phase 1 research can be reviewed here. The results of the Phase 2 research will be released soon.
Do people have to participate in these clinical studies?
Swaminathan: Participation is voluntary and requires those involved to provide informed consent – after receiving a detailed overview of the study, including possible benefits and side effects – if they want to participate. Participants also have the option to leave the study at any point. Participation in clinical trials are the only way we can find answers that will ultimately help us all overcome the COVID-19 pandemic.
How ethical is it to test people with a COVID-19 vaccine?
Gusmano: There is little question that this can be ethical, but as with all other clinical trials, it depends on the circumstances and design. If there is sufficient evidence from the bench science and animal models, it is reasonable to move to human clinical trials.
Once this happens, a vital issue is an informed consent. Questions we must ask are: Are the risks and benefits explained clearly? Have those running the trial thought carefully about the potential effects of framing on how people respond to the benefits and risks? Do they clearly understand that they may withdraw from the trial?
It is essential for all of the usual protections that Institutional Review Boards require, like carefully monitoring participants' health with provisions in place to suspend or stop trials if there are serious adverse consequences. Within these parameters, clinical trials can be conducted in a way that would be broadly accepted as ethical.
How do researchers guarantee people's safety during clinical trials?
Swaminathan: All participants in clinical trials are closely monitored and provided with any new safety information discovered about the vaccine.
The clinical trials are coordinated and monitored by an oversight Data Safety and Monitoring Board and frequently by a Protocol Safety Review Team, which is composed of the study sponsor, NIH and other federal officials. They review adverse events in real time to ensure that volunteer safety is prioritized. Both groups can recommend stopping or pausing the trial if needed. Local Institutional Review Boards also help protect the rights and welfare of study volunteers recruited to participate in the trials.
How do you know if a vaccine clinical trial is for you, and what should people know or do before volunteering to participate?
Swaminathan: In order to be eligible for the Moderna phase 3 trial, healthy volunteers must be 18 years of age or older with no known history of the COVID-19 infection and no previous participation in an investigational coronavirus vaccine. Within this population, we are prioritizing candidates whose locations or circumstances put them at higher risk of exposure to the virus, including:
- Age 65 or older
- Essential workers in close contact with potentially infected persons, including but not limited to health care and hospital workers, first responders, transit employees, institutional residents or workers, factory employees, teachers and students
- Racial and ethnic minorities at high risk for COVID-19
The study has multiple other criteria that will be reviewed with participants on an individual basis to ensure that involvement is right for them.
What are the risks associated with participating in a COVID-19 vaccine clinical trial?
Swaminathan: Enrollment in phase 3 vaccine studies is only possible because of the information from phase 1 and 2 studies. As of September 18, 2020, over 25,000 participants have been enrolled across the U.S. in the Moderna phase 3 study.
Will people be compensated for participating in a vaccine clinical trial?
Swaminathan: We respect the study participants’ time and effort in volunteering to participate in the study and they will receive some reimbursement, the details of which will be reviewed during the informed consent process.
Who will be prioritized first for the COVID-19 vaccine when it's finally approved and how will it be made available and distributed to the public?
Gusmano: There seems to be a broad consensus that health care providers, people in high-risk categories like nursing home residents and other essential workers should receive priority. But the federal government has not articulated clear standards and neither have most of the states. We also do not know enough about the number of doses that will be distributed to each state if and when a vaccine is approved. And we have not done sufficient planning around how the vaccines will be transported, stored or delivered. The Centers for Disease Control and Prevention's guidelines are vague on all of these points, and there needs to be a lot more work on this before we know how it is likely to work.