A COVID-19 vaccine is quickly becoming a reality, with Pfizer and Moderna set to obtain emergency use authorization of their vaccines in mid-December with limited distribution soon after; both of these vaccines have been over 90% effective in phase three clinical trials. AstraZeneca believes its vaccine could be available in January 2021. Understandably, there is fear and confusion about the safety and efficacy of the vaccines. Thus, I wanted this post to focus on the clinical trial process and how these vaccines have moved through the proper steps of that process despite the vaccine production being named “Operation Warp Speed.”
Clinical Trial Phases
Clinical trials for the COVID-19 (SARS-CoV-2) vaccine began in March 2020 with over 40 potential options. They are coming to a close in November and December, with only a handful of viable candidates left.
The clinical trial process for vaccines are similar to those for any other medication. There are three clinical trial phases. Weijer (2020) explains phase one trials recruit 10-100 healthy volunteers who receive varying doses of the vaccine, and phase two trials include hundreds of healthy volunteers who are more diverse. In phases one and two, vaccine efficacy is evaluated using antibodies found in blood; however, the major focus of these trials is on safety by determining adverse reactions that are very common (occurring in 10% of people) or common (occurring in 1% of people). Phase three trials primarily focus on efficacy since the vaccines have been deemed safe, but these trials also have a much larger, more diverse pool of volunteers so that uncommon (occurring in fewer than 1% of people) and rare (occurring in 0.1% of people) adverse effects can be discovered. After successfully navigating all three phases, a vaccine may be approved by the Food and Drug Administration (FDA).
Vaccines do not need to be 100% effective to be approved by the FDA; in fact, according to
Zhang (2020), the FDA has set the threshold at 50% effectiveness for a COVID vaccine.
A vaccine candidate that gets to a phase three trial is considered safe, but the safety and efficacy of the vaccine will continue to be monitored after it has been approved and is being administered. There will be rare adverse reactions as time goes on and more people receive the COVID vaccine. Rare adverse reactions happen with well-established vaccines and medications, and they aren’t uncovered by longer clinical trial processes; instead, they are uncovered by a large amount of the population receiving a vaccine. Zhang (2020) points out that the COVID-19 vaccine phase three clinical trials are much larger than traditional phase three trials which is beneficial because it will help uncover those adverse reactions that you see as more people receive the vaccine faster than trials with a smaller sample size that are conducted over years.
How is it possible to have a vaccine so soon after learning about the new virus?
It seems unbelievable that we can go from COVID-19 stepping onto the scene in December 2019 to an approved vaccine (or two or three) by the end of 2020, but it is possible.
Understanding a virus’s genetic code can greatly speed up production of a vaccine. COVID-19 began appearing in December 2019 (although at that time it was only known as a virulent strain of viral pneumonia) in Wuhan, China. On January 24, 2020, the French Ministry of Health confirmed its first three cases of the virus, and on January 29, 2020, scientists at France’s Institut Pasteur had sequenced the entire genome for COVID-19. In contrast, the HIV 1 genome wasn’t sequenced in its entirety until 2009 (Britannica, 2020), nearly 30 years after HIV/AIDS became a global health crisis.
Also, although COVID-19 is a novel coronavirus, scientists did not start from scratch developing the vaccine. There were previous coronavirus outbreaks that led to vaccine research. SARS (SARS-CoV-1) struck the world in 2002 and 2003, and MERS popped up in 2012. Fortunately and unfortunately, none of these outbreaks lasted long enough or were far-reaching enough to warrant pharmaceutical companies investing money into full-scale vaccine development, although research and laboratory testing were done in the hopes of taking a vaccine candidate to clinical trials. According to Roosinck (2020), vaccines for SARS also went through animal testing in preparation for human clinical trials.
Companies used this vaccine research from the previous coronavirus outbreaks as their base for further developing and modifying a vaccine for COVID-19. Unlike with the previous coronavirus outbreaks, because of the scale of COVID-19, there was interest across the globe in developing a vaccine. In fact, in March 2020, there were over 40 companies that were interested in taking a COVID vaccine to trial (Padron-Regalado, 2020). Also, unlike with previous coronavirus vaccines, the federal government provided the funding for the COVID-19 trials so we could have “Operation Warp Speed.”
What’s in a name? AKA, what makes this “Operation Warp Speed”?
The name “Operation Warp Speed,” has left many with the impression that a vaccine will be fast tracked and appropriate safety measures will be skipped. Biologist Preston Estep explains that “Operation Warp Speed” is not changing any of the trial processes or necessary safety measures for testing a new vaccine; instead, it is removing the financial hurdles to vaccine production. In “Operation Warp Speed,” the U.S. federal government is investing hundreds of millions of dollars into the trials to ensure the trials can happen (as cited in Sleiman, 2020). Remember earlier when I mentioned that SARS and MERS vaccines never made it to large scale clinical trials because they weren’t deemed to be worth the financial risk? That’s not happening now. Also, the HHS (2020) tells us that with the federal government financing and managing the trials for multiple vaccines, all clinical trial protocols can be aligned to better compare results. This also allows the government to pre-order doses and begin to prepare for production and distribution while the vaccines are still in the trial phase so it’s ready to go if a candidate is approved.
But the trials were paused, so the vaccines are unsafe. Right?
Moderna, Johnson & Johnson, and AstraZeneca briefly paused their phase three clinical trials after a small number of participants experienced adverse reactions. These pauses were featured in the news as if this was something uncommon; however, it is not uncommon to pause clinical trials. Also, just because a person in a trial has an adverse reaction does not automatically mean it was caused by the vaccine, so the pause helps figure out the cause of the event.
Bioethicist Ruth Faden explains that during the clinical trial process for any medication or vaccine, safety standards are set and the data and trials are reviewed by an independent board that ensures those standards are adhered to; these standards include the number of people with adverse reactions required to trigger a pause. In the case of AstraZeneca, the trial was paused after a single participant experienced adverse reactions, and this was in accordance with its safety guidelines. Faden also tells us that the risk-benefit calculation impacts the number of acceptable adverse reactions. With traditional medications, fighting a disease may allow for a greater number of adverse reactions because people in the trial are already sick, possibly dying, so the medication reactions may be minimal in comparison. But when you’re developing a vaccine, otherwise healthy people could get sick, and this “significantly heightens the risk-benefit calculus for the participants” (as cited in Skerrett, 2020) meaning trials may be paused when only one or a few participants experience an adverse reaction.
Hopefully this blog post has helped shed more light on what is happening with clinical trials and the vaccine safety, neither of which are influenced by politicians. This is information you can use when deciding whether to talk to your physician about the vaccine.