Karl W. Smith, MDT/Bloomberg
The U.S. Food and Drug Administration’s decision to recommend a pause in distribution of the Johnson & Johnson Covid vaccine has been roundly — and rightly — condemned across the political spectrum. It’s clear that the hypersensitive “abundance of caution” standard the FDA applied is inappropriate for a global pandemic. Less well recognized is that the same standard, applied during normal times, also has enormous costs for lives and health of Americans.
The FDA acted after blood clots were observed in less than one in a million people who have received the J&J vaccine in the U.S. By contrast, Covid has already killed 1,712 out of every million Americans. What’s more, from the information the FDA released initially, it was not clear that any of the blood clots were fatal, though officials later said one woman had died. By its own admission, the agency does not know if there is a causal link between the vaccine and the clotting.
Sadly, this kind of deadly overweighting of costs relative to benefits is not uncommon at the FDA.
No decision rule is perfect, and oversight agencies (public and private) inevitably make mistakes. But analysis by researchers at MIT suggests the FDA’s basic approval standards are too cautious.
These standards persist in part because it is extremely easy to measure the lives lost by a drug’s side effects, but it is nearly impossible to calculate the lives lost by a drug never having been introduced at all. Would it have mitigated the illness it was designed to treat? Would it have complemented or discouraged the development of later therapies?
All that can be said is that those standards raise both the costs and financial risks of pharmaceutical development. One of the mRNA vaccines against Covid was famously synthesized days after the virus’s genome was published. Even in the midst of a pandemic, however, pharmaceutical companies were reluctant to move forward with development without either direct support from the federal government’s Operation Warp Speed or, in Pfizer’s case, a $2 billion purchase guarantee.
The experiences of AstraZeneca and Johnson & Johnson, both of which used a more conventional approach to vaccine development, show why. In the former case the drug has still not been approved in the U.S. despite a safety profile similar to those of its competitors. In the latter, the requirements for approval were met, yet the vaccine now faces an uncertain future because of side effects that may not even be caused by the vaccine itself.
By contrast, the mRNA vaccines from Pfizer and Moderna have turned out to be slightly more effective and with side effects regulators deemed less troubling. Pharmaceutical companies, however, had no way of knowing that in advance. In fact, researchers have known for years that mRNA technology has potential as a treatment for cancer, but have been reluctant to pursue it because of high development costs and regulatory uncertainty.
If such a successful and now potentially revolutionary technology was deemed too risky even before the pandemic struck, then consider how many other therapies have been shelved before they reached that stage. Again, it’s impossible to know because pharmaceutical development is an iterative process that proceeds from the successes and failures of the past.
Even the development of therapies that never make it to market can shed vital insight that leads to breakthroughs in other areas — but only if the initial investment in R&D is made. That’s precisely what the FDA’s overly cautious standards discourage.
The Covid pandemic has laid bare the enormous resources necessary to bring a new drug to market and how easily the FDA’s regulatory process can derail those efforts. Now both the public and their politicians might see the need for better regulations that allow the full might of the pharmaceutical industry to be deployed against the health threats of the 21st century.
Karl W. Smith, MDT/Bloomberg
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