In the froth and frenzy surrounding Ebola reaching America, a surprisingly unprepared Department of Health and Human Services, particularly the Centers for Disease Control, largely failed to rise to the challenge. The FDA contributed to, and continues to contribute to, that lack of preparedness. Both HHS secretary Sylvia Burwell and President Obama’s Ebola “response coordinator” Ron Klain need to intervene.
In 2007 Congress passed legislation to spur drug development for tropical diseases. Congress authorized the FDA to award transferrable “priority review vouchers” to any company that successfully developed a drug for a list of neglected tropical diseases. Given the increasing sluggishness of FDA approval reviews, this type of incentive has proven to be popular and effective. The FDA awarded its first voucher under the statute earlier this year.
The new law listed a number of diseases, including malaria, dengue fever, cholera, and African trypanosomiasis. Oddly, it did not specifically include Ebola, but it gave the FDA authority to designate additional diseases.
The FDA response to this statutory change was so desultory that in 2009 Congress directed the FDA to issue guidance to the industry on the statute. The FDA dithered until July 2014, when it finally issued brief guidance on the topic. Despite the concurrent hysteria, the FDA did not even mention Ebola.
What’s worse is that the FDA, although theoretically acknowledging that it could approve a drug for a neglected tropical disease based on data from nonrandomized trials, essentially made it impossible to do so. Many of the countries that suffer horribly from tropical diseases simply do not have the infrastructure to run classic randomized trials for diseases that spring up on an unpredictable basis; it would also be unethical in many cases to run such trials. In other words, the FDA guidance responded to congressional concerns—and the people who suffer from those diseases—with the back of its rubber-gloved hand.
To be fair, once there was intense public and political pressure to treat public health professionals with investigational drugs, the FDA went to the limits of its authority to respond to that pressure, including apparently authorizing use of at least one drug that had been tested only on animals. The basic science for these investigational drugs was mostly familiar and low-risk, the specific animal data were supportive of safety and efficacy, and the mortality risk for the infected patients was very high. As far as I can tell from limited public data, there is no reason to do anything but enthusiastically applaud the FDA’s rare risk-taking for recent Ebola patients.
From there, the story goes downhill. Although on its website the FDA touts in detail the specific investigational diagnostic products it allowed to be used for Ebola testing, it inconsistently withholds under inapplicable legal authorities any details about the investigational drugs it allowed to be used. The FDA won’t even disclose how it approved those investigational drugs, although one official strongly implied to me that the agency relied, perhaps for the first time, on the Pandemic and All Hazards Preparedness Reauthorization Act of 2013 rather than customary “expanded access/compassionate use” laws, which allow emergency use of investigational drugs. That information, and medical data on safety, dosing, and efficacy that could almost certainly be obtained from consenting companies, would be enormously helpful to medical professionals who must respond quickly to new Ebola outbreaks.
All of the companies making serious efforts on Ebola are small ones subject to SEC requirements mandating disclosure of significant FDA actions relating to their programs; several of them are hardly publicity-shy. Ron Klain, the president’s point man on Ebola, needs to cut through the FDA’s traditional nontransparency and call together the heads of the FDA and the CDC, top experts at NIH, and the CEOs of all the Ebola companies to work together to create the best possible repository of clinical experience with the new drugs. Any treating clinician should be able to access these data immediately when the next patient appears at an unpredictable time and place.
The alternative to a constantly updated repository is forcing suddenly stressed clinicians to piece together the pros and cons of treatment alternatives primarily from fragmentary disclosures on the Internet. After that delay, they would have to petition one or more companies and the FDA without even being sure which regulatory framework the FDA will use—or how quickly. Delays in the first critical hours and days will inevitably cause deaths; yet the FDA stubbornly hoards information that could prevent those deaths.
The FDA should perceive its Ebola-related inconsistencies as a case of déjà vu. In the mid-1980s HIV activists pushed the agency into using expedited reviews to approve the early HIV drugs in record time and with far less data than the one-size-fits-all template on which the FDA too often relies.
Once the HIV activists won their war with the FDA, David McIntosh, who led Vice President Quayle’s Competitive Council, provoked a moral and medical debate within the Bush administration. He argued, persuasively, that there was no moral or medical difference between patients dying from HIV and patients dying from other diseases for which there were no approved therapies. Despite fierce resistance from the FDA, the Bush administration issued the first accelerated drug approval regulations in 1992. Shortly thereafter, the FDA used those regulations to approve drugs—drugs that would have been rejected in the past—for a variety of diseases, including rare cancers, multiple sclerosis, and fatal protein deficiencies of children. It is no overstatement to say that McIntosh’s crusade benefited millions of Americans.
Despite the success of McIntosh’s initiative, the FDA doggedly continued to undermine those regulations, which caused an angry Congress to pass corrective legislation many times on a bipartisan basis. For Ebola, as with HIV in the 1980s, the FDA needs to look at its choices allowing the use of investigational drugs and ask if it is applying the same principles to less high-profile patients dying of untreatable diseases.
A recent example of the FDA’s indefensible inconsistencies is its October decision to demand more data yet again—without clear, science-based standards—for companies seeking approval for several new drugs that should be available now to patients with the fatal disease of Duchenne muscular dystrophy. What makes the muscular dystrophy pronouncements worse is that there are signs that they are driven by the FDA’s worst cultural tendencies: retaliation behind closed doors, “leveling the playing field” for competing companies by slowing down the company in the lead, and improperly relying on outside advisers with a strong financial interest in the outcome of its decisions. As the new Congress establishes its oversight priorities, this shameful mess should be high on its list.
The FDA should learn from its mistakes. It needs to be more proactive with guidance on the standards for approval of drugs for Ebola and other tropical diseases, more transparent about the safety and efficacy of investigational drugs for Ebola, and more understanding about why randomized trials for rare diseases are often not feasible. When it comes to children dying of muscular dystrophy, the FDA needs to show more of the urgency it displayed when approving investigational Ebola drugs for heroic public health workers.
Michael Astrue is a former commissioner of Social Security and a former HHS general counsel.
