The regulations that oversee the prescription drug industry and protect consumers from dangerous products are surprisingly fragile and young.

In wasn’t until 1962 that the Food and Drug Administration starting asking drug companies to prove their products were both safe and effective before they hit the market.

Until that time there were some standards related to adulteration and labeling, but otherwise it was mostly a free for all. It took the infamous scandal around thalidomide, a morning-sickness medication that caused severe birth defects, to strengthen the FDA. An FDA medical officer, Dr. Frances Kelsey, adamantly opposed allowing thalidomide to be sold in the US — saving American families from the pain wrought by the drug in many other countries.

After that, in 1962, Congress passed the Kefauver-Harris amendments, acknowledging the importance of having independent FDA scientists comb through data about new drugs to make sure their benefits outweighed their harms.

Now, we’re living in a time when the FDA seems to be moving backward. Researchers who study the agency say the agency's standards are slowly and methodically being eroded — particularly with the forthcoming implementation of the 21st Century Cures Act. And they're worried about what’s to come under President-elect Donald Trump. After all, Trump has promised to get rid up as many federal regulations as he can, and his potential nomination of a libertarian Silicon Valley investor to lead the FDA could further weaken the agency.

The FDA is being nudged to be more lenient on drug companies

On Tuesday, President Barack Obama signed the 21st Century Cures Act into law — the biggest health reform bill since the Affordable Care Act.

The 996-page bill has some great elements (like more money for health research at the NIH, and funds to fight the opioid crisis) but it also contains language that could water down FDA oversight. And this is why health researchers who study the agency have been decrying this act since it started making its way through Congress in 2014.

"There are lot of good things in the bill," said Joseph Ross, a Yale researcher and FDA expert, "but they are all bungled together with things that undermine the FDA’s regulatory authority."

One concerning provision in the act has to do with the use of "real-world evidence" — safety monitoring data, observational studies, et cetera — for drug approvals.



Right now, before a new drug can be marketed for a particular use, the drugmaker needs to present high-quality evidence in the form of randomized clinical trials (the gold standard of medical evidence) to the FDA. The bill asks the agency to set up a program to evaluate the use of real-world data when companies are seeking approval of a new indication (or use for an already existing drug) or trying to satisfy the FDA’s post-marketing study requirements.

On the plus side, this would allow the FDA to incorporate more types of evidence than just the randomized control trial into its decision-making. But the worry is that, unlike clinical trials, these types of evidence aren't very rigorous — they’re just observations about trends, not experiments with placebo controls. The researchers I spoke to said this opens the door for data dredging, and that there’s really no way to know whether a drug is safe or effective based on that kind of research.

"It’s a lower level of evidence than the gold standard, which is randomized controlled trial," said Michael Carome, the director of Public Citizen's Health Research Group. "Real world evidence is easier to do, less expensive, less onerous. It’s easy for that type of research to be designed in a way that leads to biased results."

The Cures Act will also allow the FDA medical reviewers to use "summary-level reviews" written by drug companies when making decisions about new indication approvals, instead of raw data. Now, this provision wouldn’t require the FDA to rely on these summaries. But it gives FDA officials permission to not look at the raw data.

While this may speed up the approval process, the reviews may be biased in favor of the drugs (remember — they are created by the industry trying to get their products passed by FDA). And critics worry that, because the FDA is starved for resources, officials will wind up using these summaries more often than not.

Carome called the provisions "a stepping stone" in "the gradual erosion [of the FDA] since 1992," referring to the Prescription Drug User Fee Act (PDUFA), which allowed drug companies to pay user fees to the agency in exchange for speedier reviews of their products.

Before the PDUFA law was enacted back then, taxpayer money funded the FDA's programs related to human drug development. Nowadays, about two-thirds of that budget comes from drug companies — which, some argue, changed the dynamic between industry and FDA and created a conflict of interest since the agency now heavily relies on funding from the industry it regulates.

Separately, there’s also a push to make the FDA more lenient on another aspect of regulation: marketing.

In the US, companies can only advertise their drugs for FDA-approved indications, not so-called "off label" uses (as when doctors prescribe, say, birth control for acne). But recently, two pharmaceutical companies have turned this into a First Amendment issue, suing the FDA for violating their right to free speech.



If others follow, this will hamper the FDA's power to crack down on misleading marketing practices and encourage companies to make all kinds of claims about their products, not necessarily evidence based. (Right now, the FDA has to come up with a policy for off-label promotion after considering evidence from a public hearing on the topic.)

"There are changes of degree and changes in kind to consider," said Dr. Josh Sharfstein, an associate dean at the Johns Hopkins School of Public Health and former deputy commissioner of the FDA. "[The 21st Century Cures Act] is a nudge to move in a certain direction," he added. He doesn’t think the Cures Act will necessarily be ruinous for the agency, since there is some leeway in the language of the bill. Instead, he thinks that its provisions could allow a leader who wants to move backward on medical regulation to begin to do so.

A libertarian Silicon Valley investor with no medical background is in the running to lead the FDA

Last week, rumors started to circulate that Trump may chose Jim O’Neill, a Silicon Valley investor and associate of billionaire Peter Thiel, as FDA head.

O’Neill has no medical background, but very strong views about medical regulation. In the past, he’s basically advocated for turning the FDA back to that pre-1962 free for all. "We should reform FDA so there is approving drugs after their sponsors have demonstrated safety — and let people start using them, at their own risk, but not much risk of safety," he said in a 2014 speech. "Let’s prove efficacy after they’ve been legalized."

As Forbes’s Matthew Herper wrote, "That quote betrays a lack of understanding of how drug approvals actually work, or a commitment to rolling back the clock 50 years."

Indeed, having an FDA chief who wants to get drugs on to the market before they’ve been fully vetted could turn us back to a time before the Kefauver-Harris amendments. "[It's] a terrible idea, but O'Neill is not alone in saying this," said Harvard's Aaron Kesselheim, who has been studying the FDA. "It is an idea that has been increasingly pushed by people affiliated with the American Enterprise Institute and other conservative and libertarian think tanks."

The idea behind this push is that weighty regulations hold back drug innovation. Yet, Kesselheim said, requiring some proof that drugs work coincided with a golden age in pharmaceutical innovation, "in part because drug manufacturers knew that in order to be able to sell their drugs, they had to be able to demonstrate some evidence that they actually work to help patients."



Instead of helping spur innovation, turning back on those standards will slow it down. (You can read more here about how the speed of drug approvals isn't the bottleneck of innovation.)

Even if O’Neill isn’t Trump’s final pick, Carome of Public Citizen's Health Research Group predicts a weaker FDA in the future. "Trump has signaled a deregulatory approach in multiple areas of the government," he said, "and one would expect he’ll nominate someone to [FDA] with that same deregulatory approach."

Whoever takes the lead, changes at the FDA won’t be immediate, Sharfstein said. "The FDA doesn’t not turn on a dime and many at the agency will want to implement the new provisions responsibly … but having somebody who thinks the FDA’s main law [regarding proving drugs both safe and effective before going to market] is the wrong law at a fundamental level would be a real danger." And, at the forthcoming Trump FDA, that danger seems imminent.