How Can We Be Sure the New COVID-19 Vaccines Are Safe?

* What is Phase III Testing?
“These are rigorous investigations, closely monitored for safety and for efficacy; they ensure that the vaccine’s side effects are minor and that they resolve, and that the vaccine prevents COVID-19. They also measure the strength and duration of the immune response in a large, randomized cohort.”

The emergency approval process currently underway for two vaccines is based on two months of phase III testing data. That is the recommendation of the FDA’s independent advisory committee for an emergency situation like we’re in now. We want to end the pandemic, so we want to get things done as fast as possible. That’s why two months is not unreasonable for people who have the highest risk of COVID-19 exposure and the lowest risk of adverse vaccine reactions – people who have more to gain from a vaccine – such as primary care providers and first responders. If I were in this group, I would say, “OK, two months will do for me.”

But for people at lower risk of contracting COVID-19 – those who can work from home, for example – but at higher risk of medical complications, then I think when to get vaccinated becomes a personal decision. They may want to wait until we accumulate more information from longer follow-up times – perhaps six months from the start of the phase III trials.

Understanding different options; reaching the global population

JAIME SEPÚLVEDA, MD, DSC, MPH

Professor of epidemiology and biostatistics; Haile Debas Distinguished Professor of Global Health Sciences; executive director, UCSF Institute for Global Health Sciences

There are currently 13 vaccines in phase III trials. Three of them – those made by Pfizer, Moderna, and AstraZeneca* – have completed their efficacy and safety studies, and two are in the process of seeking emergency use authorization from the FDA. According to information the manufacturers provided, different age groups and ethnicities were included in the vaccine trials. Based on those reports, it seems that even in people over 70 years of age, the response is very positive. However, it is important to have peer-reviewed scientific publications confirming both the efficacy and the safety of the different vaccines.

Vaccines produced in China and Russia have apparently been applied to selected local populations. Some experts think this rushed preliminary approval carries risks since phase III trials have not been completed.

The ideal vaccine would accomplish three endpoints: prevent infection, reduce the severity of the illness if someone does get the disease, and interrupt the chain of transmission. It is unlikely we will have one single vaccine doing all three. It is possible that different vaccine technologies may offer different advantages with respect to these distinct goals.

Equal allocation of vaccines globally will be of paramount importance to ending the pandemic because as long as SARS-CoV-2 exists somewhere, it will be everywhere. The World Health Organization has proposed guidelines to ensure that vulnerable populations have access to vaccines and has participated in creating a platform for funding and distributing a COVID-19 vaccine globally. However, reaching at least 70% of the global population with two doses of vaccine – an estimate of the vaccination coverage needed to achieve worldwide herd immunity – will be a major challenge.

Building trust across communities

STACY TORRES, PHD

Assistant professor of social and behavioral sciences, UCSF School of Nursing

I have an autoimmune disease, Sjögren’s, which puts me in a higher-risk group that may be encouraged to receive the vaccine before younger, healthier people. So I monitor the safety of vaccine development and distribution from a very personal place. To achieve the vaccinated population percentages that would allow us to more safely resume in-person interactions, we will need a concerted effort to overcome growing distrust of vaccines among the public.

For example, if I saw Dr. Anthony Fauci take the vaccine on TV, I’d feel much more comfortable taking the vaccine myself and urging family members to comply, especially those who are vulnerable to COVID-19 complications and death due to underlying medical conditions and/or advanced age. I point to Dr. Fauci as one exemplar of a trusted public health expert, but we will need to enlist a wide range of trusted partners* to work with communities of color and those across a range of abilities, ages, legal statuses, sexualities, etc., to instill confidence in the vaccine and help keep the complex distribution process exquisitely transparent.

Relying on multiple independent reviews

SUSAN BUCHBINDER, MD

Clinical professor of medicine, epidemiology, and biostatistics; director, Bridge HIV, San Francisco Department of Public Health

I will feel confident that a vaccine is safe after multiple independent groups have reviewed the safety data. Here’s how it works for any vaccine seeking emergency approval:

First, an independent group of experts, the Data and Safety Monitoring Board, reviews safety and efficacy data from the phase III vaccine trials. Then the FDA staff and their independent vaccine-advisory committee do their own reviews. Safety is one of the FDA’s top priorities when the agency considers whether to recommend that emergency use authorization be granted to a vaccine, including for COVID.

The Centers for Disease Control and Prevention’s advisory group, the Advisory Committee on Immunization Practices, also reviews the data in order to make recommendations about which populations should be first in line to receive the vaccine.

Finally, in California, we have an independent group of scientists and public health experts who will also review the safety and efficacy data before distribution begins. And then the data will be published, so we will all be able to review them. With all of those layers of review, I feel confident that a vaccine that is rolled out in California will be safe and effective for use.

That said, it’s worth addressing the popular notion that as soon as we have a vaccine, life will go back to “normal.” The ultimate achievement of herd immunity – population-wide protection – will rely on whether and to what extent the vaccine keeps people from being infectious. We know that some of the vaccines reduce the virus’s severity – fewer people who got the vaccine got sick than those who received the placebo. We will need some other studies, currently being planned, to tell us whether it is also keeping people who become infected from passing the virus on to others. We don’t have all that data yet. So for now, we are going to need both a vaccine that induces high levels of protection against infectiousness, and a population willing to receive a vaccine*.

Look to the FDA’s review and statewide infrastructure

LISA KROON, PHARMD

T.A. Oliver Professor and Chair, Department of Clinical Pharmacy, UCSF School of Pharmacy

I’d first look to the FDA’s rigorous evaluation process for COVID-19 vaccines. Despite the unfortunate insertion of politics into the handling of the pandemic, I turn solely to the science, which is what the FDA reviews. Knowing that many Americans may be apprehensive to use a vaccine that was developed at light speed, the FDA has made a commitment to being open and transparent with the public about their process to make safe and effective COVID-19 vaccines available. I’ve been impressed with how the companies developing the vaccines have made their data on safety and effectiveness so readily available to the public. I expect the FDA to follow suit with their announcements about emergency use authorization and/or licensing approvals.

In California, the governor’s COVID-19 Vaccination Plan and COVID-19 Testing Task Force provide all the infrastructure you’d really hope for – including a community advisory committee to ensure equitable decision-making around distribution plans and a scientific workgroup to review safety and efficacy data as specific vaccines become available on a state level. I am confident that our process* will be highly organized and coordinated, with distribution handled in an ethical manner.