Yesterday a panel of outside experts — formally known as the Vaccines and Related Biological Products Advisory Committee — and laypeople convened to advise the U.S. Food and Drug Administration (FDA) on how to make the approval process for Covid-19 vaccines safer, more robust, and deserving of public trust. One thing became clear over the course of the seven-hour meeting — that a hastily expedited vaccine might benefit some people, but fail those who need protection most.
The primary objective of the ongoing late-stage vaccine trials, which have involved hundreds of thousands around the world, is to prevent the onset of Covid-19 symptoms in half of everyone vaccinated. What we really need from a vaccine, however, isn’t a broad reduction in mild cases, but mitigation of serious illness and death. The probing of the advisory committee, as well as presentations that featured insights and concerns from everyday folks, raised issues with the current regulatory framework that are threefold: efficacy, safety, and access.
First and foremost is the issue of efficacy, or how well a vaccine candidate actually works when administered to the general public. The purpose of vaccinating against a disease as lethal as this one — a disease that has claimed more than a million lives since the beginning of the pandemic and brought harm and devastation to millions more — shouldn’t be to stop the majority of people from getting colds. It should be to protect the elderly and infirm, Blacks and Latinos, and other groups who are becoming critically ill and dying from Covid-19 at disproportionately higher rates.
As of now, this isn’t the case. Earlier this month, the FDA published a set of stricter guidelines for clearing Covid-19 vaccines — ostensibly against the wishes of their White House overseers, who held up their release for weeks. One of the new criteria is that some members of the control group — those participants receiving a placebo rather than the vaccine — need to develop severe symptoms. While intended to create some parameter for evaluating efficacy against serious disease where none existed beforehand, the magic number candidates must meet is startlingly low. Of the 30,000 people participating in a clinical trial, it only takes five cases of severe Covid-19 in the control group to tick this particular box. We cannot assume that a vaccine protective against mild illness will do the same for critical illness, and so long as we can’t assume it we must do better to prove it.
The second issue discussed during yesterday’s meeting, not mutually exclusive from the first, is safety. Another criteria included in the updated FDA guidelines is a two-month monitoring period following the completion of phase III trials, notably pushing the potential timeline for any candidate well past Election Day. While the requirement of following up with participants to ensure the vaccine provides the protection it promises — not to mention doesn’t trigger any harmful side effects — is absolutely necessary, two months is hardly enough time to conduct a rigorous long-term evaluation.
Human coronaviruses are some of the wilier threats we’ve faced from the microbial kingdom in decades, and studies show that they’re not just capable of reinfection, but potentially even linked to antibody-induced enhancement — meaning antibodies created against the virus enhance its capabilities upon reentry. If we don’t thrust the horizon of Covid-19 vaccine development beyond just a few months, we risk creating entirely preventable challenges that will play out over several years.
This brings us to the third issue the panel raised — access, or who will receive a vaccine and when. It appears that emergency use authorizations (EUAs), as Helen Branswell of STAT News astutely observed, have perhaps fallen out favor with the FDA and the general public, who have seen treatments like hydroxychloroquine and convalescent plasma receive authorization based on preliminary data, only to later be discredited by clinical and anecdotal reports of ineffectiveness or even harm. For the same fate to befall an emergency authorized vaccine — especially knowing that in the early days of rollout, doses will go to priority groups like healthcare workers and nursing home residents — would be nothing short of a humanitarian crisis.
Instead, FDA representatives at the meeting floated the idea of distributing vaccines through a program of “expanded access” — a mechanism that, rather counterintuitively, would be more limiting in scope than an EUA and might potentially resolve an issue known as early unblinding. If a vaccine is approved through an EUA, members of control groups in ongoing clinical trials will naturally want the real deal rather than a placebo, all but eliminating the opportunity to obtain the long-term data on efficacy we need. While the alternative of “expanded access” raises the question of who, exactly, so limited a notion of access will privilege, once in effect it wouldn’t necessarily impede clinical trials.
Recent surveys reveal that the number of Americans willing to get vaccinated as soon as they’re able has dropped significantly — more so for Black Americans than white. On the flip side, the fear that political interests will override scientific evidence as the primary criteria for vaccine approval is on the rise. The vaccine advisory committee meeting can serve as a catalyst for the FDA to reverse course, slow down, and introduce more regulatory rigor to a process that has largely gone off the rails. Now is not the time to take a gamble and try our luck on a shaky candidate.