hen it comes to reviewing drugs, the FDA’s job seems straightforward: make sure a drug is safe. Then make sure that it actually works and does what it is supposed to. It’s an essential mission that this deeply dysfunctional organization appears to be having trouble fulfilling. The EpiPen pricing scandal and the controversial approvals of flibanserin (Addyi) to improve underactive sexual desire in women and eteplirsen (Exondys 51) for treating Duchenne muscular dystrophy illustrate that the FDA appears to be having trouble following its own guidelines.
I have been working in investigational drug development for almost two decades. As a politically conservative medical scientist at the FDA — a supreme rarity, I assure you — who has worked as a medical officer and senior medical analyst, and as a former investigational medicine research scientist at Pfizer, I haven’t always agreed with regulatory decisions made by the FDA.
Lately though, in addition to disagreeing, I now fail to understand several of the FDA’s decisions in the very recent past. In addition to a profound lack of scientific proof, these decisions seem to lack basic common sense. For example, flibanserin worked in only 8 percent to 13 percent of the women in which it was tested. On top of this pathetically poor efficacy, flibanserin can have life-threatening interactions with recreational alcohol consumption and some of the most commonly prescribed antibiotics and antifungals on the market.
Eteplirsen’s recent approval by the FDA was deeply disquieting and, like flibanserin, also sets a terrible precedent. Eteplirsen was tested in a mere 12 individuals, with no control group — a highly unusual situation when it comes to evaluating an investigational medicine. In addition, the drug increased production of a key dystrophin biomarker protein needed for improvement by less than 1 percent of normal overall, which is neither clinically nor scientifically meaningful.
As a former FDA medical officer and erstwhile FDA observer, I offer seven of my many suggestions for fixing the agency.
Fix the broken hiring process. The FDA’s inability to hire enough qualified staff members has been an unaddressed problem for well over a decade. This hampers its ability to carry out its mission. Take, for example, the approval of money-saving generic drugs. The FDA has a backlog of as many as 4,000 applications to produce such drugs because it doesn’t have the staff to review them. Part of the problem is a broken hiring system through USAjobs.com, where all applications must initially be submitted. There, human resources managers with little or no scientific training review the applications of highly specialized scientists. To make matters worse, it’s impossible for the best and brightest in academia and industry to directly call a recruiter at the FDA, because there is no publicly available list of FDA recruiters.
(Editor’s note: If you have your own suggestions for improving the FDA, please share them here.)
Institute consequences for bad decisions. Most FDA staffers and supervisors are highly qualified, dedicated individuals from dozens of different disciplines. That said, the FDA would benefit from a good personnel sweep. The agency has its share of petty people who have personal agendas against fellow FDA employees and/or pharmaceutical companies. Firing FDA employees who have attained federal “career” or “permanent” status — which amounts to university tenure — is difficult. They essentially have to be caught red-handed breaking the law in order to be fired.
Some FDA staffers in powerful positions make bad decisions, or have views that aren’t in line with mainstream, evidence-based science. Directors, deputy directors, or others should be held directly accountable when they incorrectly approve a drug, unnecessarily hold up approval of one, or implement bad decisions, just as would happen in private sector jobs. Unfortunately, most of what happens in internal FDA meetings is never made public, so it is often difficult or impossible to hold individuals accountable.
Negotiate disagreements between reviewers and management. Reviewers are responsible for conducting the hands-on component of drug analyses. They summarize what sometimes amounts to tens of thousands pages of data for others at the FDA, including management. If management (who did not conduct the review) disagrees with the in-the-trenches reviewer, that reviewer currently has no recourse except to obey his or her supervisor. Reviewers should have the option to contact an outside group of scientists — possibly a congressionally appointed committee. And the facts of such disagreements (which occurred with both flibanserin and eteplirsen) should be made public.
Better collect and monitor safety and adverse event reports. The FDA is doing a poor job compiling adverse events and reporting them to health care professionals and the public. Adverse event tracking through the FDA Adverse Event Reporting System (FAERS) or MedWatch has the power to provide valuable real-time sharing of new drug safety issues that did not emerge during clinical trials. Unfortunately, the time-intensive process of reporting an adverse event to a drug company or the FDA is neither a requirement nor goal for prescribers, physicians, and pharmacists who are already burdened with overwhelming amounts of paperwork for insurance companies, Obamacare, and electronic medical record requirements.
Play a role in drug pricing. The FDA currently has no say when it comes to the actual price of drugs. Congress should create an offshoot of the FDA similar to the United Kingdom’s National Institute for Health and Care Excellence. It independently reviews and recommends drugs within the same class, based on their safety, efficacy, and overall merit and benefit. This is something we could definitely learn from the FDA’s European counterpart, the European Medicines Agency.
Stop abusing startups and small drug companies. Like it or not, the US depends on private drug companies to invent and develop new drugs for existing and emerging diseases. I have personally attended numerous FDA meetings during which typically smaller drug companies that needed help developing drugs were verbally abused and demeaned by FDA staffers. FDA employees who are hostile towards private pharmaceutical companies trying to help the world through legitimate development of new medicines should be held accountable for such abusive behavior. Some sort of public rating system should be created that will let drug companies publicly evaluate the helpfulness of FDA employees.
Improve the quality of advisory committees. The FDA often solicits advice from independent advisory committees on how to proceed when clinical questions arise. To be part of an FDA advisory committee, however, an individual must not have accepted any research funding or speaker’s fees from a drug company or have any conflicts with the drugs being reviewed. Because the best and the brightest scientists are usually doing original or novel research, often funded by industry, this eliminates many of the most qualified individuals. As a result, today’s advisory committees are usually made up of retired physicians and scientists who aren’t leaders in their fields, and aren’t always up to date on the latest clinical developments. Advisory committee members need to be a lot better than they are, which will make their opinions hold more weight.
These items are just the ones at the top of my list. I could easily triple or quadruple the wish list.
I recognize that higher-priority issues with the incoming administration include the economy, the repeal of Obamacare, illegal immigration, and terrorism. But I still hope that Tom Price, President-elect Donald Trump’s choice to lead the Department of Health and Human Services, puts the many serious problems at the FDA under special scrutiny.
David Gortler, PharmD, PhD, is a professor of pharmacology at Georgetown University and a former FDA medical officer, now a pharmacology expert and FDA expert with FormerFDA.com. He was also the FDA/health care policy advisor for the 2016 Ted Cruz presidential campaign.