Lawsuits endanger FDA role on approvals

Lawsuits endanger FDA role on approvals

By Jon Bigelow

While media attention has focused on the availability of abortions, take note: contradictory court decisions about mifepristone broadly threaten the authority of the Food and Drug Administration (FDA) to approve and regulate new medications for any indication.

Second-guessed by both sides

On April 7, Judge Matthew J. Kacsmaryk of the U.S. District Court for the Northern District of Texas — ruling in a case brought by anti-abortion groups — revoked the FDA’s 2000 approval of mifepristone for use in medication abortion. Kacsmaryk alleged that the FDA had “acquiesced on its legitimate safety concerns” under political pressure. This is believed to be the first time a court has invalidated the approval of a drug over the FDA’s objections.

Reaction was immediate. Supporting the ruling, 69 Republican members of the House and Senate charged that “the FDA’s unlawful approval and deregulation of chemical abortion drugs subverts Congress’ public policy considerations and safeguards for patient safety.” On the other hand, more than 400 leaders from the pharmaceutical industry signed a letter stating, among other things, that “if courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone.”

The Justice Department immediately appealed the Texas ruling to the Fifth Circuit Court of Appeals, which imposed a temporary stay and heard arguments on May 17.

On the same day as the Texas ruling, April 7, Judge Thomas O. Rice of the U.S. District Court for the Eastern District of Washington — ruling in a case filed by Democratic attorneys-general from 17 states and the District of Columbia — granted a preliminary injunction that ordered the FDA not to limit the availability of mifepristone in those states.

In effect, the FDA is being second-guessed by partisans from both sides of the abortion debate. The appeals will take time to work through the courts and, for now, mifepristone remains available. But given the conflicting decisions, it appears highly likely that both cases will eventually land before the Supreme Court.

Four reasons to be concerned

Whether mifepristone will remain available is an important issue, and although the final decision probably will be made by the same justices who recently overturned Roe v. Wade in a 6-3 decision, the legal questions are different and the outcome is uncertain.

But the court decisions will go far beyond the abortion issue, either reinforcing the authority of the FDA to determine what pharmaceuticals become available or inviting political interference in decisions about any drugs, for example vaccines, Alzheimer’s disease therapies, opioids, or gender-related agents. Consider a few of the implications.

First, the current regulatory process for drug approvals has served our nation well; for good reason it is widely hailed as “the gold standard for the world.” It is a science-driven framework for evaluating whether products under development are safe and effective. The process has evolved as knowledge has grown, for example to incorporate new data sources, improved trial protocols, and needs when the target patient population is small or no alternative therapies are available.

The FDA’s talented, dedicated professionals work collaboratively with the pharma industry while still maintaining independence. Yes, there have been occasional problems, but for years the FDA’s processes have brought a continuing flow of innovative new agents into clinical practice, with very few serious issues. It is hard to see how this process — or patient care — would be improved by greater political or judicial involvement.

Second, the current regulatory process is central to a drug development ecosystem involving clinical trial investigators, pharmaceutical companies, contract research organizations, and other key players. Investment in R&D already involves considerable risk, few compounds survive all the way to FDA approval. To inject the additional uncertainty of politically-motivated lawsuits that pull products off the market before companies have recouped their investments will diminish the incentives for investing in any potential therapy that might address an “unpopular” patient population or clinical need.

Third, success in undercutting the FDA’s authority to make science-based decisions in these cases may encourage further challenges.

We are only three years removed from the early days of the COVID-19 pandemic, when politicians urged the FDA to authorize emergency use of chloroquine or oleandrin without evidence of clinical efficacy and when President Trump accused the agency of being part of a “deep state” conspiracy to delay approval of a vaccine to damage his re-election prospects. More recently, Axios has reported unattributed threats of political payback from Republicans on the House committee overseeing FDA funding.

It’s also worth remembering that in early 2017, the new Trump administration was widely reported to be actively considering for FDA Commissioner persons with little relevant experience but strong opinions on reshaping the drug approval process — approving an agent based only on early evaluations of safety, and letting the marketplace determine whether it is actually effective. That would risk allowing on the market ineffective agents and delaying patients from receiving effective alternatives. It also would put small entities with incentives to cut corners on a par with the ethical pharma companies that have well-honed (albeit expensive) R&D processes, fueling a rush to the bottom.

Where would it stop?

Fourth, partisan court challenges feed public distrust in the FDA. Commissioner Robert Califf, M.D. is working diligently to reinforce the FDA’s reputation after the pandemic stresses. These efforts will be significantly undermined if the current court cases limit the FDA’s authority. As Califf said in an April 10 interview with MedPage Today, “Once you open the floodgate of political appointees making decisions about drug approvals or device approvals, where would it stop? I’d urge you to think about some of the politicians that have been elected in America. Would you want them reaching in with the connections to companies that they have and overruling the decision of full-time civil servants?”

So, the outcome of the dueling legal challenges on availability of mifepristone will be important for all of us —as health communicators and as patients.

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