June 28, 2017
By Karl Thiel for BioSpace.com
We’re living in volatile times. If I were to put a positive spin on that, I’d say that we’re living in times where a lot of accepted ways of doing things are being questioned. And those questions can be healthy.
Take the FDA, for example. Pretty much every new president pays at least some lip service to the idea of speeding up drug approvals, cutting red tape, and helping the life sciences become more innovative. But President Trump apparently seriously considered appointing Jim O’Neill or Balaji Srinivasan as FDA Commissioner. Both O’Neill and Srinivasan are associates of Silicon Valley libertarian/iconoclast Peter Thiel, and have argued that drugs should be approved on the basis of safety alone, with the “market” deciding on whether they’re effective. (Healthcare is hardly a market in the normal sense of the term, hence the quotes.) O’Neill in particular would have done away with most clinical trials altogether.
Now, let me stipulate that it’s not clear how seriously Trump was considering O’Neill—the former HHS official seemed pretty quickly eclipsed by other candidates, and obviously it was Scott Gottlieb, more of an “insider” choice (though probably more radical than many people realize), who ruled the day.
But a more interesting question is whether O’Neill might have had the germ of a legitimate point.
I don’t mean doing away with efficacy trials—that would be disastrous on multiple levels. But the idea that the “real world” can teach us things about drugs that clinical trials can’t has been steadily gaining momentum over the past few years.
The “Thwarted Cures” Fallacy
Yet while there may be a right way to go about getting more real-world data and relying less on the kinds of clinical trials we do now, there are a whole lot of pitfalls. And unfortunately, O’Neill and Srinivasan’s ideas are exemplars of a broader school of fallacious thought that I’ll call the “Thwarted Cures” fallacy. It is a pernicious fantasy that is particularly prevalent on the political right, but also extends to the left. And before we can talk about how clinical trials might be reformed, it’s important to consider why some of the most popular ideas on the subject are so dangerous.
Many conservative ideologies hold that regulation is the enemy of progress, an unfortunate (if, grudgingly, in certain cases, necessary) brake on economic growth. And there are certainly many examples where that’s true. Given that pharmaceuticals are heavily regulated, it makes some sense at first blush to imagine that innovation is especially stifled in this industry.
However, that’s very little evidence that FDA is standing between consumers and better drugs. While most people who deal with FDA will happily tell you ways in which the agency could be improved, it is biology rather than red tape that trips up the vast majority of drug programs. Most people who work inside the industry know that. (O’Neill and Srinivasan, notably, never did.) They understand that, despite vast effort and great advances, our understanding of biology is very spotty. They’ve seen drugs perform well in phase 2 only to flame out in phase 3, even when it’s not the fault of trial design or a greedy rush to the finish line.
Moreover, those acquainted with statistics know that when it comes to clinical trials, we are looking for a tiny signal amidst a lot of noise. Drugs that cure everyone don’t actually need a ton of statistical analysis to demonstrate their worth. But many of the drugs that do make it to market have incredibly modest benefits or, in a striking number of cases, no proven benefit at all. The idea of lowering barriers and putting drugs with even more questionable virtues on the market—which is the most optimistic interpretation of what radical deregulation would mean—would have society being forced to pay for more medicines that do little, do nothing, or actually hurt patients.
But it’s not just the political right who imagines a sea of cures held back by malevolent forces. Some on the left may see the actors and motivations differently, but the outcome is similar: Patients are denied valuable medicines for selfish reasons.
One of the clearest examples of this is the explosion of “right to try” laws, which have proliferated to 37 states since the first one passed in Colorado on 2014. These were actually born out of the libertarian Goldwater Institute, but they are seen by many through the lens of activist campaigns from the 1980s, like ACT UP and other AIDS advocacy groups. Most “right to try” laws (and they are all nearly identical) allow a terminally ill patient to try any medicine as long as it has passed phase 1 testing. (Never mind that these state laws cannot supersede the FDA’s federal regulation of drugs.)
Simple statistics will tell you that the hope this provides to dying patients is almost entirely false—the vast majority of these medicines will be proven worthless, and potentially dangerous. Moreover, right-to-try laws rather toothlessly provide no means for patients to actually access these drugs—they don’t compel doctors to prescribe the drugs, nor companies to provide the drug, nor insurers to pay for them. That’s actually a good thing, since if patients were actually receiving medicines in an unregulated fashion, we’d undoubtedly see deaths or uncontrolled, unblinded “miracles” that would hamper actual clinical development.
FDA is on pace to approve a near-record number of novel drugs this year. Reform can be good—it could potentially create a better understanding of the drugs we get—but let’s not forget how good we have it now. More on reform next month.
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