Miguel Paniagua, 48, blocked off his morning on Thursday, Sept. 17. Normally, he spends his weekdays either developing assessments for medical students as a member of the National Board of Medical Examiners, teaching students at the University of Pennsylvania’s school of medicine, or working in palliative care at one of the university’s hospitals. But on that morning, right at 8am, he walked into one of the university’s vaccine trial sites to begin a three-hour screening process that culminated with a quick jab in his right upper arm.
The University of Pennsylvania has partnered with Moderna to run one of the company’s phase 3 clinical trials for a Covid-19 vaccine. Paniagua is one of what will be tens of thousands of participants receiving either the new mRNA-based vaccine, or a placebo. So far, Paniagua says he feels fine. “The first three days I had some moderate soreness in my deltoid where they injected me, not unlike where I get a flu shot every year,” he says. “I don’t know what that means… If it was the vaccine, I didn’t have a severe reaction.” He posted a selfie on Twitter the next day.
To get emergency use authorization from the US Food and Drug Administration (FDA)—a status that would fast-track production and distribution—Moderna has to show that the vaccine is safe and effective for eight weeks after the second of two injections. (Paniagua will get his second injection in about three weeks.)
That timeframe is both prolonged and not: It’s long enough to make sure that, for most people, the vaccine is safe and has no long-term side effects, but short enough that Moderna could conceivably scale up and produce millions of doses by mid-2021 if the trial is effective. (The US has already pre-ordered millions of doses from Moderna.) Normally, vaccines take over a decade to make, from research to manufacturing to distribution; with the Covid-19 pandemic, pharmaceutical companies have been asked to do it in a little over a year. The best way to ensure these trials get done quickly is for everyone who can participate to do so. “To me, it’s my duty,” Paniagua says. “I took an oath regarding my patient care.”
One participant among thousands
Paniagua know’s he’s in a good position to help Moderna generate data on their vaccine candidate. For one thing, he gets regular exposure to Covid-19 through his work practicing palliative medicine. Once a week, he could potentially be exposed to someone who is dying of Covid-19 or other complications. Additionally, his wife is also a physician; she, too, could come into contact with the virus. Some exposure is necessary to assess if the vaccine works.
Paniagua is also Latino, a group that has been historically marginalized and neglected by the US medical community. As the pandemic has progressed, it’s become clear that Covid-19 disproportionately affects the Black and Latinx community. These groups have to be included in these trials to make sure that they’d actually benefit from a vaccine’s protection.
Paniagua heard about the trial through an internal communication from his employer; after filling out an online questionnaire assessing his eligibility, he received an email from someone running the trial, scheduling a date for him to come in. When he arrived, he received a physical assessment, including a Covid-19 screening, and gave 10 vials of blood so that the trial could assess other baseline measures of his health. Paniagua also had a chance to meet with the trial’s principle investigator to ask questions. Once those were answered (no, he can’t donate blood during the trial, because it would reveal whether he’d received a placebo; yes, he can get his annual flu shot), he got a jab, a thermometer, and instructions to download a smartphone app. The whole thing took less than three hours.
Paniagua will receive $225 in compensation for participating in the trial. For about a week after each jab, he’ll need to fill out a daily symptom diary, and update the team if he develops any unexplained symptoms or Covid-19 itself. He’ll also do follow-up visits, and will have at least a phone call a month with the trial’s investigators for the next 25 months—more than two years.
Any outcome is valuable information for Moderna. If Paniagua got the real shot and has reactions, it could indicate that the vaccine isn’t safe for him for whatever reason. If he got the shot and still gets Covid-19, it could be that the vaccine was ineffective or only partially effective. If he took a placebo but still gets sick, it could mean that the vaccine actually worked in people who got it. (If Paniagua does get sick, Moderna will send a doctor to his home.)
Gaining FDA authorization
Normally, the FDA approves vaccines, a process that involves carefully evaluating three phases of clinical trials, each with more participants than the last. After the FDA signs off on a candidate, manufactures get to mass producing.
We don’t have time for that with Covid-19. Instead, the FDA is planning to give vaccine candidates emergency use authorization—a status that means, given the state of the pandemic and the fact that there are no other alternatives, if the vaccine seems safe and effective based on the best available data, companies will be allowed to manufacture it and providers will be allowed to administer it. The US government has preemptively bought millions of doses of vaccines from various companies, even before results from their clinical trials are ready. Essentially, this means that the government is eating the cost of research; if a vaccine doesn’t work out in a late-stage clinical trial, the drug company won’t have lost money on mass producing it overall.
Even on an accelerated timeline, regulators have to factor in safety. Earlier this week, the Washington Post reported that the FDA would be upholding specific guidelines for authorizing a Covid-19 vaccine: First, all trials will have had to follow participants for at least two months after they receive their final injection. Second, at least five people will have to get severe cases of Covid-19 after receiving the placebo, which would indicate that the real vaccine was sufficiently effective at preventing these infections.
The data safety monitoring boards are charged with holding Covid-19 vaccines to the same standard as any other vaccines, says Paul Offit, a pediatrician who led the development of the rotavirus vaccine and served on the Advisory Committee on Immunization Practices to the US Centers for Disease Control (CDC). Most vaccine safety trials require at least 42 days of follow-up, or six weeks; two months, therefore, seems right in line.
For other vaccines, this two-month period is long enough to observe any common side effects caused by the vaccine itself. But what it won’t be able to catch are uncommon side effects, those that occur in only a handful of individuals. Offit says those types of side effects—like Guillain-Barre syndrome, a progressive paralysis—wouldn’t show up in clinical trials anyway. That’s why it’s important to keep monitoring vaccines even after they’ve been developed.
“That’s true of any medical product,” Offit says. “That’s why we have to be honest about what we know and what we don’t know. The question is when do you know enough.”
US president Donald Trump, eager to have a vaccine before the election on Nov. 3, has said that he may reject the FDA’s guidelines for authorization. Trump told reporters on Wednesday that he believes delaying the vaccine’s approval is a political move, rather than a scientific one. But scientists would likely be highly skeptical of a vaccine deployed on a faster timeline; without the data from clinical trials, it’s impossible to assess whether or not it would actually work. And an ineffective vaccine is just as bad as no vaccine at all.