Safety Implications of Regulatory Rollback at the FDA

Prescription drugs in recent years have experienced breathtaking price hikes and occasionally have proven dangerous after they have gone on the market. What is happening with these issues since the Trump administration took office? For one, President Trump announced recently his intention to roll back FDA regulations as much as 75%.  Scott Gottlieb has just been named Trump’s choice to lead the FDA, and he as well as the other two candidates, Jim O’Neill and Joseph Gulfo, called for streamlining regulatory procedures. Jim O’Neill even called for drugs to be tested only for safety.

Once marketed, individuals can take new drugs “at their own risk” and thereby prove – or disprove – their effectiveness.

All adults as they age are more likely to take not just more drugs but drugs for both acute and chronic conditions. These individuals, with few exceptions, take prescription medicines because they need them to stay alive, to manage conditions adequately enough to be functional, or to dull chronic or acute pain. Taking drugs for them is not a choice—they have no option but to “take the risk.” Under O’Neill’s plan, prescription medications intended for life-threatening conditions could end up killing these people if they turn out to be ineffective, an outcome that is all too likely given that an average nine out of ten new drug candidates prove unsuccessful.

Furthermore, the need to take such unsafe risks is not spread evenly across the population.

Lower income individuals, although they do not take more prescription drugs than higher income individuals, suffer from higher rates of chronic and life-threatening diseases. They, then, would be impacted the hardest.

Though data on gender is not plentiful, one 2014 study found that out of a sample of approximately 30 million individuals, women overall are more likely to use prescription drugs than are men, with 67.5% of women utilizing prescription drugs versus 58.9% of men. In the 18-44 age group the difference was even greater, with 64.1% of women versus 48.6% of men utilizing at least one prescription drug. Women also overall took a higher number of prescription drugs, 5 on average versus 3.7 for men.

These statistics evidence the fact that, though everyone who takes prescription drugs is at risk of regulatory rollbacks – and in the space of a lifetime, this includes most people – women are at more risk given the higher number of prescription drugs they consume.

Frighteningly, despite being prescribed more drugs, women are less frequently given the clinically recommended medications for particular . For example, they are less likely than men to be given the recommended medications for cardiovascular disease or diabetes. Women with histories of coronary artery disease receive cholesterol-lowering drugs at significantly lower rates than men with the same history – 59% vs. 71.5%. Down the road, this could mean that women are at higher risk of inadequately-managed coronary artery disease, while men receiving the latest cholesterol-lowering drug or beta blocker will be at higher risk of adverse reactions from inadequately tested new pharmaceuticals.

One potential reason for Trump to trim regulations is to speed the approval of drugs, something that on the surface seems like a good idea. The faster a new drug can be approved, the faster it can get to market and to the people who need it. And indeed, it takes a long time to get a new drug approved for market: an average of eight to twelve years.

Yet, the current approval process emerged for a reason: it was implemented and revised in response to preventable tragedies arising from unsafe drugs.

The original Pure Food and Drug Act of 1906 was strengthened in 1938 when an anti-infective elixir called Dr. Massengill’s Elixir Sulfanilamida killed 107 individuals. Public fear resulting from these deaths led Congress to pass a bill that strengthened labeling of food, drugs, and cosmetics, and also gave the FDA greater power to seize products. The thalidomide tragedy, when hundreds of babies were born with no or underformed limbs to women who had taken thalidomide during pregnancy, prompted Congress to pass the 1962 Kefauver-Harris Amendments. These Amendments, among other things, enabled the FDA to prevent new drugs going to market, and created the three-phased, randomized controlled clinical trial structure required today for thoroughly testing a drug’s safety, dosing, and efficacy. With the AIDS epidemic, the FDA created a fast-tracking mechanism to get drugs approved more quickly in urgent circumstances. This concession came only after intense and consistent campaigning by early AIDS activists tired of seeing hundreds die while new pharmaceuticals were showing the promise in early-phase testing of keeping them alive.

Though certainly not infallible, the FDA’s current set of regulations and procedures for drug and new device approval are there for good reason: there is little doubt they succeed much of the time in shielding the public from the worst consequences of what can happen when drugs, vaccines, or devices are not properly vetted.

Indeed, in a report released last year, the FDA noted twenty-two drugs that had shown promise in early-stage testing (which tests for safety) but had failed late-stage, Phase III testing (which tests for efficacy while continuing to test for safety). Seven of these twenty-two failed to prove either safety or efficacy in Phase III trials.

Returning to the question of time to approval, expedited approvals themselves, once the exception at the FDA, are now becoming more the norm. A recent article from The New England Journal of Medicine shows that in 2013 more than 60% of new drugs were fast-tracked through the approval process. In addition to the AIDS drug-related fast tracking program, the FDA now has four more programs enabling pharmaceutical companies to receive expedited approval for drugs, for example, for rare diseases, breakthrough therapies, and even for antibiotics. Yet as the authors of the NEJM article note, this is not necessarily a good trend. Expedited review is typically intended for patients with urgent conditions who have no other options, and as such, the FDA requires less evidence of safety or efficacy for these therapies.  For that reason, though, the expedited review is often time-limited and approval granted contingent upon a promise of further testing even while making the expedited drug available in humanitarian cases. Nevertheless, given the FDA’s wide latitude in defining what qualifies for expedited approval, pharmaceutical companies are increasingly fast-tracking drugs because it means earlier time to market, not because it means saving more lives.

There is also little doubt that in recent years the FDA has come under fire for long delays in drug approval that are not related to testing, but rather to how long it takes new drug, vaccine, or device applications to wind their way through the approval process.

One of these problems is due to the vicissitudes of funding that the FDA, like all federal agencies, experiences with changes in administration. As noted by one commentator, there are about one thousand vacant seats at the FDA right now, which inevitably has to cause delays.

Despite this barrier, the FDA set a goal to approve standard new drugs within ten months, and expedited drugs within six.  For 2016, they met that ten-month average goal, and almost met the priority approval goal. In contrast, in 1993 average times to approval were twenty-seven and twenty months, respectively. Now, however, Trump has issued a hiring freeze, which is likely to undermine this progress.

Rolling back regulations at the FDA would not accomplish the efficiency that Trump wants. On the contrary, slashing the budget would ensure that seats remain empty and that more become empty, resulting in fewer experts to make the approvals still necessary even with regulatory reductions, and consequently, longer approval times. Fewer regulations would put individuals at vastly higher risk when consuming new pharmaceutical drugs and vaccines or utilizing new devices. These risks could be relatively minor, but they could also be catastrophic.

To add such significant safety risk to prescription medications inadequately tested before marketing is inhumane; it treats individuals as guinea pigs while the risk of injury is unevenly spread by income and by gender.

No one needing prescription drugs would be spared the unconscionable risk entailed in allowing new drugs, vaccines, and devices to be marketed with little testing, and equally little knowledge about whether they are safe or effective. The one optimistic note here is that several pharmaceutical companies themselves have pushed back on Trump’s recommendation. They note the uncertainty this would lend to the FDA and its approval system, and cite as well the safety issues that would inevitably result. If the pharmaceutical industry doesn’t even want rolled back regulations, why should Trump?

Susan Craddock, Acting Director, Center for Bioethics; Professor, Gender, Women and Sexuality Studies and the Institute for Global Studies, University of Minnesota

— Photo by Meghana Kulkarni