President-elect Trump’s leading candidates to head the Food and Drug Administration oppose regulations that require drugs to be safe and effective.
By Michael White
In the late 1950s and early ’60s, thanks to an official at the United States Food and Drug Administration, Americans escaped one of the largest avoidable medical disasters in modern history. Dr. Frances Kelsey, an FDA physician, refused to approve a United States license for a popular European drug, thalidomide, because she was worried that the data indicated the drug was unsafe. More than 10,000 children worldwide were born with birth defects caused by thalidomide, but only a dozen or so were affected in the U.S., thanks to Kelsey’s caution.
This close call in America, and thalidomide’s disastrous effects elsewhere, led directly to the legal framework that governs how drugs are regulated in the U.S. today. While some drug safety regulations were established early in the century, laws passed in 1962 and ’63 required, for the first time, that drug companies scientifically demonstrate that their products are both safe and effective before marketing them.
Jim O’Neill thinks that the FDA should let companies sell drugs without first showing that they work.
But the people reported to be Trump’s leading candidates to head the FDA think we should be scrapping these regulations. Trump, who is being advised on the FDA by technology billionaire Peter Thiel, was reported in December by Bloomberg to be considering venture capitalist and Thiel associate Jim O’Neill for the job. And, last week, Bloomberg reported that another Thiel associate was also in the running: Balaji Srinivasan, an engineer and former biotech executive. Unlike previous FDA commissioners, neither O’Neill nor Srinivasan is a doctor or clinical scientist, though O’Neill did serve as an associate deputy director in the Department of Health and Human Services (of which the FDA is part) during the George W. Bush administration. Both O’Neill and Srinivasan, and Thiel as well, have questioned whether pharmaceutical companies should be required to show that their drugs are safe and effective before selling them to patients.*
O’Neill thinks that the FDA should let companies sell drugs without first showing that they work. In a speech at a biotech conference in 2014, O’Neill complained about the heavy regulatory burden faced by the fledgling biotech companies that his investment company supports. He argued that “We should reform FDA so it is approving drugs after their sponsors have demonstrated safety and let people start using them at their own risk.” This, he suggested, is a way to get promising new therapies into the hands of patients more quickly.
But this idea fundamentally misunderstands the science of clinical trials. Any study that will confidently tell you that a drug is safe will also tell you something about whether it is effective. And, in fact, as anyone who has read the warning labels on a prescription bottle knows, no drug is completely safe. When the FDA considers a new drug, its main task is to decide whether the drug’s benefits outweigh its risks. In 2006, the FDA actually approved thalidomide as a cancer drug. Doctors, too, have to consider a drug’s risks and benefits when deciding how to treat their patients. Without good data showing how well a drug works, doctors would be left with little to go on except small, inconclusive studies and the marketing spin of the drug company.
Srinivasan has expressed even more radical views about the role of the FDA, largely in a series of tweets that he deleted shortly after visiting Trump Tower in January. Astoundingly, he tweeted last year that “Drug development prior to FDA shows that modern regimen is not necessary for safe innovation.” This claim has no basis in reality; before modern FDA standards, the drug market was flooded with bogus and dangerous patent medicines, and even some effective drugs were formulated with other toxic ingredients. But, as Mother Jones recently reported, Srinivasan thinks he has a solution. He tweeted that “New tech also allows far better regulation than FDA.” This “new tech” would let you rate your drugs the way you rate your Uber driver: “Scan a drug barcode, get 1000 worldwide MD opinions and 1 million patient self reports.”
In other words, he’s proposing to toss out scientific studies altogether, replacing FDA-mandated clinical trials with an enormous pile of useless anecdotes that are likely to be heavily biased. Clinical trials rigorously compare patients who take an experimental drug with a control group that is given a placebo or alternate therapy, and they rely on well-defined medical outcomes to establish the drug’s success or failure. When done properly, these trials avoid confounding factors that bias the conclusions, such as when a drug falsely seems to work better than the alternative simply because it tended to be prescribed to healthier patients. Bias can be an enormous problem. For example, some early studies, which lacked appropriate control groups, reported that hormone-replacement therapy reduced the risk of heart disease in women after menopause. This turned out to be the opposite of what more rigorous, less-biased studies found — that hormone replacement therapy, in fact, doesn’t lower, and may increase heart disease risk. Srinivasan’s million patient self-reports may sound like a lot of data, but, unless they were organized into a proper study, these reports would offer little of value.
And finally there are the views of Thiel himself. According to Fortune, Thiel gave a 2015 speech in which he said that the FDA should permit drug companies to sell drugs that are less effective, but cheaper than the best drugs on the market. In other words, those who are less well off will have to be satisfied with inferior drugs, while the rich get the best that science can devise. Aside from the harm this will cause to patients, this idea also puts doctors in an impossible bind: Should they knowingly give their patients drugs that don’t work as well?
The common thread that binds the ideas of O’Neill, Srinivasan, and Thiel together is that their proposals for reforming the FDA clearly represent the interests of biotech investors, and not those of the patients and even doctors who the FDA exists to protect. Investors like Thiel and his associates are constantly exposed to persuasive pitches from entrepreneurial biomedical scientists who think they’ve come up with a promising idea for some new treatment or medical device. Once you’ve invested in a biotech start-up founded on one of these supposedly brilliant ideas, it’s tempting to view the FDA’s regulatory standards as an unhelpful barrier that stands in the way of success.
But part of the job of the FDA commissioner is to recognize that most promising ideas in biotech and drug development will fail — not because of excessive regulation, but because medical science is challenging. Given the high failure rate of experimental drugs, it is critical that the FDA enforce high standards. History shows us what happens without these standards: We’ll be ripped off by high-tech patent medicines, or become the pharmaceutical industry’s unwitting guinea pigs.
*Update — January 19, 2017: This post has been updated to reflect the fact neither of the candidates are clinical scientists.