On April 13th, citing "an abundance of caution," after the appearance of a few rare blood clots in the brain (cerebral venous sinus thrombosis, or CVST) following administration of the Johnson & Johnson COVID-19 vaccine, the FDA announced a "pause" in its administration. Regulators reversed course just ten days later, after confirming that the incidence of that adverse reaction was, indeed, extremely low, and that the benefits of receiving the vaccine overwhelmingly outweighed the risks.
The decision to pause was precipitated by six cases of the CVST clots in the U.S., in women between the ages of 18 and 48 who had received the vaccine. By then, almost seven million shots of the one-dose vaccine had been administered in the U.S., according to the FDA. As of May 13th, with over 8 million doses of the one-shot vaccine having been administered, the number of people who had experienced the "thrombosis with thrombocytopenia syndrome" (translation: "clot with low blood platelets") had risen from six to 23.
As a result of the FDA's April 13th announcement, many state and local public health agencies put administration of the J&J vaccine on hold at a time when vaccines were in short supply, and the frequency of new cases of COVID-19 was significant. More broadly, regulators seemed oblivious to the predictable chilling effect that their action would have on Americans' willingness to be vaccinated by any COVID-19 vaccine. Their precipitous action slowed the momentum toward getting as many people vaccinated as quickly as possible and, thereby, was harmful.
INCENTIVES FAVOR BUREAUCRATS' EXCESSIVE RISK-AVERSION
The FDA-mandated pause was short-lived, but as the saying goes, it's hard to un-ring the bell: that is, to forget certain pejorative information, even in light of subsequent moderating events. As a result of the FDA's mandated pause, it has become harder to inoculate the vaccine-hesitant. Many people canceled appointments during the temporary pause and haven't rescheduled, which has made reaching community vaccination goals more elusive. A survey by the Kaiser Family Foundation found that, "In the wake of news about blood clots possibly linked to the Johnson & Johnson COVID-19 vaccine and the subsequent pause in the use of this vaccine, less than half the public expresses confidence in the safety of the Johnson & Johnson vaccine, and concerns about potential side effects have increased among those not yet vaccinated, especially women."
Given the baseline of hard-core vaccine-resistant Americans, any increase in those hesitant to get a COVID-19 vaccine is a setback. We know that "herd immunity"—the point in a pandemic when enough people have either recovered from or have been fully vaccinated against an infectious disease, and there are no longer enough susceptible people in the population (the herd) to sustain transmission—is unlikely to be achieved for COVID-19, so, to keep the herd safe, we must strive to minimize the number of susceptible people. Practically speaking, that means achieving as close to universal vaccination as possible.
The FDA's action was damaging, but not surprising, in view of a long-standing pattern of excessive risk-aversion at the Agency. The late, great economist Milton Friedman had an explanation. He observed that to gain insight into the motivation of an individual or organization, look for self-interest. So, where does the self-interest of regulators lie? Not in serving the public interest, as one would hope, but in expanded responsibilities, bigger budgets, and grander bureaucratic empires for themselves. And, above all, staying out of trouble.
There is a widespread misconception that more-stringent regulation is synonymous with greater safety. In fact, the net benefit to patients is often compromised because of a regulatory anomaly that was evident in the J&J vaccine pause: the asymmetry of outcomes from the two types of mistakes that regulators can make. A regulator can commit a "Type 1" error by permitting something bad to happen (approving a harmful product like a drug with delayed side effects), or a "Type 2" error by preventing something good from becoming available (not approving a beneficial product in a timely way).
Both outcomes are bad for the public, but the consequences for the regulator are very different.
The first kind of error is highly visible, causing the regulators to be attacked by the media and patient groups and investigated by Congress. This is what happened in 1976 after the FDA hurriedly approved a vaccine to prevent an expected epidemic of deadly "swine flu." The epidemic never materialized, but about 450 people were afflicted with Guillain-Barre syndrome, a rare neurological disorder marked by progressive paralysis, after getting the 1976 flu shot. But the second kind of error—keeping a potentially important product out of consumers' hands—is usually a non-event, eliciting little attention. This is when the bureaucratic mindset—self-protection—gets in the way of public interest.
Drug manufacturers hesitate to antagonize the FDA or alarm investors by making too great a fuss over delayed approvals and most often comply with the FDA's demands for additional data or jumping through other hoops. The FDA's bias toward more career-friendly Type 2 errors means that regulators tend to be overly risk-averse about the approval of new products—or, as in this case, about allowing the distribution of a life-saving product.
Food and Drug Administration website.
WHEN BUREAUCRATS PUT SELF-INTEREST ABOVE THE PUBLIC INTEREST
Former FDA Commissioner Alexander Schmidt aptly summarized the regulator's conundrum: "In all our FDA history, we are unable to find a single instance where a congressional committee investigated the failure of FDA to approve a new drug. But the times when hearings have been held to criticize our approval of a new drug have been so frequent that we have not been able to count them. The message to FDA staff could not be clearer." Former FDA General Counsel Peter Barton Hutt echoed Schmidt, asserting that "FDA employees have been praised only for refusing to approve a new drug, not for making a courageous judgment to approve a new drug that has in fact helped patients and advanced public health."
As a result, regulators make decisions defensively—in other words, to avoid approvals of harmful products at any cost—so they tend to delay or reject new products of all sorts, from fat substitutes to vaccines and painkillers. That's bad for public health and for consumers' freedom to choose.
We need FDA reform of several kinds. We need to insulate policy-making and decisions on individual products from politics (insofar as that is possible), make regulators' decisions more data-driven, and improve pharmacovigilance—the monitoring of the safety of already-marketed drugs. Finally, we need to redress the culture of excessive risk-aversion and defensive decision-making that pervades the FDA. (That is Congress's role, but they have shown little appetite for it: a premature or mistaken approval makes for more exciting hearings, with injured patients and their families paraded before the cameras).
As to the J&J vaccine pause specifically, a more judicious decision from the FDA and its sibling agency, the CDC, would have been to recommend that administration of the J&J vaccine be limited to men and to women above the age of 60, while more data were accumulated and analyzed. Another possibility would have been simply to inform the as yet unvaccinated population of the (very low) risk of serious adverse events from the J&J vaccine, and let them decide whether to take the shot. Either of these options would have better reflected an appreciation of the need for risk-benefit assessments to take into consideration the "big picture."
There is an implicit contract between society and civil servants like those who populate the FDA: the bureaucrats are insulated from political influence and retribution and, in turn, are supposed to make decisions solely on the basis of scientific evidence and public health considerations. Unfortunately, self-interest too often intrudes on their calculus.
Henry I. Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. He was a research associate at the NIH and the founding director of the FDA's Office of Biotechnology. You can find him online or on Twitter at @henryimiller, and read more of his writing at henrymillermd.org.