Congress is trying to speed up Food and Drug Administration drug approvals, but the problem is science, not regulation.
By Michael White
Given the terrible state of our politics, this will be hard to believe: Our lame duck Congress is about to pass a major piece of legislation with overwhelmingly bipartisan support. Though it has failed to pass a budget or hold a vote on the president’s Supreme Court nominee, the 114th United States Congress is about to come together and pass a $6 billion bill that boosts funding for biomedical research, makes significant changes to how the Food and Drug Administration approves new drugs, and provides $1 billion for state programs to combat opioid addiction and other mental-health issues. Two years in the making, the so-called 21st Century Cures Act passed the House of Representatives on November 30th by a large bipartisan vote of 392 to 26. The Senate is expected to pass the bill within the week, and Barack Obama has indicated that he will sign it.
Such bipartisan lawmaking might seem like a refreshing change in an era of political stalemate, and in some ways it is. This bill does some important things: It gives the National Institutes of Health an additional $5 billion for biomedical research, provides money for state substance abuse programs, strengthens privacy protections for patients in medical studies, and fosters better data sharing among scientists.
But, like any major bill, the Cures Act has some ugly compromises. The additional money for the NIH, unlike most research funding, comes with strings attached — it must be spent on specific programs, like Vice President Joe Biden’s cancer moonshot initiative. Much of the bill is paid for by cutting money from an Obamacare fund that supports important public-health efforts like anti-smoking programs and Alzheimer’s disease prevention. The bill also loosens the rules that require drug companies to report certain kinds of payments they make to doctors, such as covering the costs of textbooks, medical journals, and courses.
One of the most significant problems with the bill, however, is that one of its major premises is flawed: the idea that medical innovation is being slowed by outdated, inefficient regulations that govern how the FDA approves new drugs. “In the 21st Century, medical innovations are moving at lightning speed,” writes Michigan Congressman Fred Upton, one of the bill’s main sponsors in the House. “But when the pace of laws and regulations don’t keep pace with these innovations, we all lose.” Upton and the bill’s Congressional supporters argue that the FDA is keeping life-saving treatments out of the hands of patients by being too slow to approve innovative new drugs. They argue that new types of clinical trials that include fewer patients, take less time, and cost less money would make drug development more efficient without compromising patient safety. The bill thus includes provisions, developed in consultation with FDA officials, that have the agency consider alternate types of evidence for a drug’s effectiveness, other than the randomized clinical trials that are the current scientific gold standard.
Critics of the bill, which include Senators Elizabeth Warren and Bernie Sanders, argue that the FDA provisions are a giveaway to drug companies, allowing those companies to market drugs without providing rigorous evidence that they actually help patients. According to Jerry Avorn and Aaron S. Kesselheim, two health policy experts at Harvard University, the bill’s FDA provisions were introduced by “political forces” that could “lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit.”
More importantly, even if we accept the need for modernizing FDA regulations, we should reject the idea that the agency’s regulations are the main problem. The development of new drugs is slow, not because regulations are too tough, but because medical science is hard. Even if the FDA were to quickly approve nearly everything submitted by drug companies — and some argue that’s basically what it’s already doing — we would still lack effective drugs for many diseases.
One key line of evidence that science is the problem, not regulation, is this: Most drugs in development fail because they prove to be ineffective or too toxic, well before they are ever submitted to the FDA for approval. A broad 2014 study of failure rates for new drugs found that most candidate drugs that are tested in early, phase 1 clinical trials fail to make it to the final, phase 3 trials that are required before FDA approval. And of the drugs tested in phase 3 trials, nearly 30 percent fail. These are drugs that don’t work, at least for the medical indications they were tested for — and no amount of regulatory streamlining will change that fact.
Furthermore, failure rates vary greatly by disease. Drugs designed to treat more challenging and less well understood diseases, such as cancer and brain diseases, have the lowest success rates. This shouldn’t be surprising: Diseases, ultimately, are driven by events that happen at the level of molecules and cells; that is also the level at which drugs act. Adding to the challenge is the fact that, at the molecular level, a disease like breast cancer or heart disease comes in many different forms. To successfully develop a drug, it is often critical to understand the multiple molecular causes underlying a disease, something that takes years or decades of research.
A clear demonstration of how difficult it is to develop drugs for a partially understood disease is the recent failure of pharmaceutical company Eli Lilly’s highly anticipated Alzheimer’s drug, solanezumab. As people live longer, Alzheimer’s is growing more common, and yet we have no drugs to treat this devastating disease. Solanezumab is one of a new class of potential Alzheimer’s drugs that targets what researchers long believed was the molecular cause, the accumulation of plaques of proteins called “amyloids” in the brain.
But on November 23rd, Lilly announced that it was ending a major clinical trial of solanezumab, because the drug failed to show any benefit in patients with symptoms of early-stage Alzheimer’s. What’s not clear though is whether this drug failed because the drug itself was flawed or because our theory of what causes Alzheimer’s is wrong. We won’t know the answer until the results from trials of other drugs that also target amyloid proteins come in over the next few years. And if our understanding of Alzheimer’s is wrong, it’s not clear what other theory, and what other types of drugs, we should turn to next.
Given the current state of medical science, many, if not most, candidate drugs will fail. The question we need to ask, then, is not whether FDA regulations are too burdensome, but how effective the agency is at stopping unsafe or ineffective drugs from coming on the market. Certainly the FDA should have the flexibility to consider alternate forms of clinical trials when they are appropriate—as long as it doesn’t waver in its commitment to only approve therapies that are highly likely to be safe and effective. But if we truly want to accelerate the pace of new cures in the 21st century, then the key is not to change regulations, but to invest more in science — something which the Cures Act does, and which Congress should do more of in the future.