Follow the science. That’s the guiding principle we’ve been encouraged to use when deciding what information to listen to about COVID-19, and it’s a sound one. So that same principle is what should guide us as we gauge the safety and effectiveness of the vaccines we’ve all so fervently hoped will provide a path out of this global pandemic.
The U.S. the Food and Drug Administration (FDA) and its independent Vaccines and Related Biological Products Advisory Committee (VRBPAC) are set to meet on December 10th to review and question the vaccine trial data presented to them by Pfizer, and a similar meeting is expected to take place around December 17th to review the Moderna data. If the data withstands the rigorous scrutiny of these two scientific bodies, and they agree that the vaccines offer a high level of protection against COVID-19, the FDA could quickly act to approve the request for Emergency Use Authorization (EUA), which paves the way for distributing the vaccine in the U.S.
Too slow or too fast of a pace?
There’s been plenty of controversy about the timing of the vaccine research. It hasn’t been quick enough for some, and others are concerned that vaccine safety and effectiveness may be compromised by the expedited timeline. Again, following the science provides the most reassuring answers to these concerns.
The vaccines currently being evaluated didn’t develop overnight. Years of research going back to previous viral epidemics such as SARS, MERS and Zika provided the framework for the current vaccines. Modern technology took that basic framework and filled in the specific genetic code of COVID-19 at lightning speed, a stunning feat that Dr. Anthony Fauci described as “a reflection of the extraordinarily exquisite – breathtaking in some respects – advances in science which are allowing us to do things in weeks to months that formerly took years.”
Human clinical trials are another part of the vaccine development process that previously plodded on for long periods of time. Assembling the needed resources and volunteers for clinical trials of over 70,000 people was done with laser-focus and major collaboration between government and the private sector (the Pfizer trials had over 40,000 participants; the Moderna trials had 30,000). It came together quickly because there was no time to lose, with a surging virus that’s already claimed over 270,000 lives in the U.S. alone. Defense Department logistical support and federal dollars assured the process moved along at “warp speed.” Moderna, for example, didn’t have to wait for an air handling unit needed at a factory, or for a specialized pump to make the first batches of the vaccine. Each time the government team assigned to support their efforts intervened to get what was needed in record time.
Do we know everything, or do we know enough about what is known?
The clinical trials data awaiting final government review were not assembled until there was enough of it to provide reliable analysis. Pfizer, in fact, delayed its first look into the trial results because they wanted a larger data set to analyze. The delay of about a week, coupled with a raging virus claiming more and more victims, did indeed create a larger data set. The initial review of data from Pfizer was encouraging: on November 9th they announced the vaccine was testing at a 95 percent effective rate. Moderna followed with a similar announcement a week later – their vaccine was 94.5 percent effective in fighting off the coronavirus.
Scientific scrutiny of what is known, that is, the science used to create these vaccines, and the studies analyzing the Phase 3 clinical trials, can provide the evidence needed to move forward with confidence.
While this positive news is exciting, the scientific community has a major responsibility to fulfill: it must provide a final, thorough vetting of processes and trial results that the public can understand and use to answer their questions. Certainly, there are answers we can’t yet know, such as what may be revealed after years of follow-up studies. But scientific scrutiny of what is known, that is, the science used to create these vaccines, and the studies analyzing the Phase 3 clinical trials, can provide the evidence needed to move forward with confidence. All eyes will be on the December 10th meeting of the FDA and the VRBPAC because this is when the public will get the evidence – both the trial data and the scientific evaluation of that data.
All eyes will be on the December 10th meeting of the FDA and the VRBPAC because this is when the public will get the evidence – both the trial data and the scientific evaluation of that data.
What is known about development of the vaccines?
The Pfizer and Moderna vaccines are based on models developed after the viral outbreaks that occurred in the opening years of this century (the SARS outbreak, for example, occurred in 2003). Called a messenger RNA vaccine, or mRNA, this model doesn’t depend on inactivated or weakened strains of the virus to work.
Instead, the vaccine delivers only the genetic code of the coronavirus protein (called the spike protein) that infects human beings. The genetic code is harmless, but it does stimulate the body to make antibodies that will fight against an actual encounter with the virus. It’s as if the vaccine simply displays a picture of the harmful parts of the virus, and that’s enough information to trigger the body into producing antibodies to fight off the real thing.
The beauty of this type of vaccine is that once the harmful genetic code of a virus can be identified, that code can be inserted into a vaccine to deliver immunization from it. Identifying the code is a complex process that requires modeling a nearly infinite number of shape combinations that define it, but technological advances have dramatically cut down the time it takes to cover this vast territory. In the years to come, if another deadly virus surfaces, this same “plug n play” system should be able to produce a vaccine in record time, just as the system has worked this time around.
What is known about the clinical trials of the vaccines?
The headline news – that the Pfizer and Moderna vaccines proved to be about 95 percent effective in clinical trials – created excitement and optimism, but that said, many questions must still be asked and answered. What we know so far is from the vaccine makers themselves. The phase 3 clinical trials involved testing the vaccine on humans. Some in the trial received the vaccine, while others were given a placebo.
Pfizer’s announcement highlighted the following:
- Among 43,000 trial participants, 170 confirmed COVID-19 cases occurred, with 162 in the placebo group and eight in the vaccine group;
- There were ten severe cases of COVID-19, with nine of the cases occurring in the placebo group, and one in the vaccinated group. This is a significant finding which may indicate immunizations will avert many deaths and hospitalizations;
- The vaccine was generally well-tolerated, though side effects noted included 3.8 percent experiencing strong fatigue and 2 percent with serious headaches;
- The vaccine was effective across age, gender, race and ethnicity groups. The effective rate in adults over age 65 was over 94 percent.
Moderna results showed:
- 196 cases of COVID-19 occurred among the 30,000 participants. 185 of those cases were in the placebo group, and 11 in the vaccinated group;
- Thirty severe cases of COVID-19 were reported, with all of them occurring in the placebo group. Getting to 100 percent effectiveness against severe cases of COVID-19 is “remarkable,” according to Paul Offit, an infectious disease and vaccine researcher at Children’s Hospital of Philadelphia;
- No serious side effects were identified, though adverse reactions were more frequent and stronger after the second dose. Pain and redness at the injection site and fatigue were among the most commonly reported side effects;
- The vaccine was effective across demographic groups, with more detailed data to come.
When do we know enough?
“It would be great if we could do a three- to four-year study and look at length of efficacy and the duration of efficacy,” says infectious disease and vaccine researcher Paul Offit. “But the question isn’t when do you know everything here – it’s when do you know enough,” he concluded.
The FDA has promised a transparent and open process as it evaluates the entirety of vaccine data and procedures. A deep data dive may help answer questions such as:
- The vaccines require two doses to be fully effective, but what is the effective rate after just one dose?
- How effective is the vaccine in high-risk subgroups, with detailed breakdowns by age, race, gender, ethnicity, etc?
- What is the full range of side effects and their severity? Are there any discernable patterns of side effects occurring within subgroups or being triggered by other factors?
- Is there any evidence of the vaccine affecting other known health problems?
- Are there factors that may affect how long the vaccine will protect against the virus?
- What is the breakdown of vaccine ingredients and their known interactions?
The data reflect up to two months following the second dose being administered. While this may not seem like a long period of time, the range of more serious side effects showed up within six weeks of the second dose. Short of the long-term follow-up that will be years in the making, the trial period has provided hard data that can be examined with scientific rigor. “It would be great if we could do a three- to four-year study and look at length of efficacy and the duration of efficacy,” says infectious disease and vaccine researcher Paul Offit. “But the question isn’t when do you know everything here – it’s when do you know enough,” he concluded.
Vigilance will serve us well in the coming months
Assuming that all goes well and there’s a go-ahead for the Pfizer and Moderna vaccines sometime this month, it’s not like a switch gets thrown and the virus disappears. There’s a long winter ahead, and staying disciplined about mask wearing, maintaining social distancing, and aggressive hand washing and sanitary practices will be key to keeping the ravaging effects of COVID-19 as low as possible. There may be a light at the end of the tunnel, but we still need to be careful to not get sick or die before we get to the other side of this dark COVID-19 tunnel.
The logistics of getting a vaccine out to a country of 330 million inhabitants will be a herculean task that the United States is certainly capable of, but it will take time. In the course of whatever comes next, remember that science may not always offer fast, easy answers, but rigorous and independent inquiry – the hallmarks of good science – will eventually lay the public health groundwork for our society to again flourish and grow.
