Skip to Main Content

When 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.

Unlock this article by subscribing to STAT+ and enjoy your first 30 days free!

  • FDA CDRH has allowed “select” industry mfrs to mislabel cervical corpectomy devices as “non-cervical VBR systems” for bogus uses in the back. FDA ortho reviewers can’t deny they don’t know how to recognize cervcial spinal cages [ So either they were in on the fix to sham-label cervical corpectomy cages or they were duped. No legally marketed predicate, no evidence-based clinical data. Scores of Americans harmed with no disclosure of device-use risks or actual safety profile consistent with cervical design rationale. Why? Because they are sham-labeled for use in the back. #FDAFail #NoConsent

  • I would nominate an engineer to lead the FDA, and especially, the device unit. They do not let planes fall out of the sky, or build bridges that collapse. They understand materials safety. They understand the concept of Precision Devices and Precision Medicine (testing to insure “right for you” and your allergies, immune system and genetics), making sure you get the right kind – not the wrong kind – of gas in your car. They look at the big picture and study all the data – the wall built between medical and dental records and health impacts would come down. Imagine the possibilities!

    In addition, FDA needs to reboot the Expert Advisory Panel system where specialists in an organ or body part review and make decisions about devices that are inserted in that organ or body part. To understand systemic impacts, all Panels should also include an allergist, immunologist, geneticist, functional medicine physician, and biologic dentist. You need all of the elephants in the room to consider benefits, risks, and ways to modify and limit risks of installing devices with 24/7/365 impacts on a genetically and medically diverse population.

  • Your article makes the common mistake of forgetting about the “F” in FDA. The FDA has a Center for Food Safety and Applied Nutrition. What it does, or does not do, affects millions of people. CFSAN needs to ensure all food ingredients are safe. It must:
    • Obtain greatly increased funding to protect the safety and ensure honest marketing of everything in our food supply.
    • Ban, restrict the use of, or require warning labels on foods that contain additives that cause heart attacks and strokes (excessive levels of sodium), obesity, diabetes, and tooth decay (sugars, high-fructose corn syrup), cancer (aspartame), adverse behaviors in children (food dyes), and severe allergic reactions (mycoprotein).
    • Stop widespread deceptive labeling that makes foods appear more healthful or of higher value than they really are.
    • Stop inappropriate uses in farm animals of medically important antibiotics to reduce rates of antibiotic-resistant antibiotics.
    • Stop the marketing and deceptive labeling of worthless (and sometimes dangerous) dietary supplements.
    • Require that companies that add unapproved substances to their foods under the “generally recognized as safe” (GRAS) rule ensure that such substances are indeed safe based on reviews of public, peer-reviewed data by objective scientists without conflicts of interest.

    • Michael, good comment. With all due respect, CSPI really needs to look into the latest research on harm from the ADA’s favorite product that fueled its growth, mercury dental amalgam, especially for those with genetic susceptibilities who don’t clear it well so it bioaccumulates. There is arguably an even greater danger from what we chew with than what we eat. Time to pay attention to that as well.

  • “As a former reviewer I would like to comment on Dr. Gortler’s proposals.

    Fix the Broken Hiring Process – Agree

    Institute Consequences for Bad Decisions – The problem is what is a bad decision is in the eye of the beholder. I have seen where managers openly admit that drugs don’t work and still approve them knowing that people will be killed. Yet such acts are rewarded. As for petty individuals with personal agendas my concern is that it is exactly these individuals who will use such an ability to fire staff.

    Negotiate Disagreements between Reviewers and Management – 100% agree. This is Dr. Gortler’s best advice

    Better Collect and Monitor Safety and Adverse Event Reports – This would be nice and a system similar to the yellow card system used in UK might be useful

    Play a Role in Drug Pricing – While nice, I don’t know if this will fly and it’s not part of the FDA’s current mission

    Stop Abusing Startups and Small Drug Companies – I seen this on occasion. However more often start-ups will come in for a meeting that is designed to address whether they have sufficient animal data to start human studies and instead want to talk about their financial issues or the studies for proving efficacy and the NDA submission. Things which are either irrelevant or should be addressed in a separate meeting later in the development process. On other occasions small companies will simply not listen to scientific and regulatory advice even when what they are proposing is scientifically invalid and contrary to specific requirements in the Food Drug and Cosmetics Act. Abuse typically comes more from the senior managers for example refusing to meet with small companies when they do need some hand holding, or not informing them that the studies that they are proposing are unethical as they can’t provide any useful information. This is not only dangerous for the study subjects but it wastes the resources of the small company and could cause them to go under. Also managers will schedule meeting after meeting with large companies to go over the same issue time and time again in order to pressure reviewers to agree to what the large company wants, while dismissing requests to meet from smaller companies. As for rating reviewers this can and will be abused. Typically when large companies don’t like the advice that a reviewer is giving them they will make false complaints about the reviewer. This can also happen internally when managers are angling for personal advantages and want to show a company that they are on their side.

    Improve the Quality of Advisory Committees – Many times Advisory Committees are not so much for advice on the science but for advice on judgment decisions as to risk vs. benefit. Such advice could be better served by including not top researchers but by practitioners who deal with patients. Also the slant is too much to even patient representatives from organizations funding by Pharma who push for approvals. A balance with patient representatives who have been hurt and may be more attuned to potential risks may strike a better balance in certain areas.”

  • As someone else said – my comments to reform the agency didn’t get posted either . My recommendations are : 1. Stop fighting pt. rights movements like Right To Try . Stop defending the broken so called ” compassionate ” use system . Your paperwork took hours, days for oncologists to complete . You admitted as much when you cut your paperwork to a supposed ” 45′ ” timeframe. I say you should get a simple, notification e – mail only that a pt. is taking a drug that has already passed Phase I safety in the trials that you are already getting data on . Rec. # 2 : Join pts. in advocating that ALL the recommendations of the Andrea Sloan Comp. use reform act be brought into law. The 21st century Cures Bill only passed one of the 4 recommendations made in memory of Andrea Sloan and so many others who could not get any compassion from either the FDA or Pharma. The only recommendation 21st Century passed was that co.’s post a compassionate use access policy and contact info. Wow , big whoop ! No GAO oversight, no task force for reform , no increased openness about how the FDA uses ” adverse events ” to deny, delay approval. We pts.’s know that Pharma is conning us when they blame the FDA only – Big Pharma gives out about 2500 compassionate use requests a yr. , for all ” terminal ‘ illnesses in a country of 314 million . We know they see dying pt’.s as ” investment risks ” . But your bureaucratic , slow 20th century , 7 – 10 year long partial, restricted approval system is a BIG part also. . So , Rec. # 3 : Be open to innovations like a rolling approval system . Rec. # 4 . More Transparency in general, for ex. Admit mistakes like you made in denying early approval to Kadcyla in 2010, and delaying Iclusig and Lemtrada in 2012.
    Up here in Boston , large healthcare systems have learned that admitting that you can make mistakes goes a long way towards decreasing pt. anger . Does that ever happen in D.C. ?

  • Shut down, restructure for limited reach and STOP being bought and paid for by big pharma?

    Do what’s right for all people not just the few greedy people. Acknowledge that corporations are NOT people with rights!”

  • Since the recommendations made to improve the agency did not get posted, let me just we need a “Precision Device” Framework, with prescreening each individual for biocompatibility to ensure a device is “right for you” before it is installed. Regarding the FDA Center for Devices’ Dental Unit, at one time they created a new element of the periodic table, “Dental Mercury,” and said it was Class I. They ignored the majority sentiment of its own expert Dental Products Panels in 2006 and 2010. The ADA holds the nation’s health hostage to a product on which it was founded, and on which its affiliate held patents. Genetic susceptibility to mercury toxicity is fairly common, and mercury off-gases from amalgams with heat and abrasion. Why play Russian Roulette with our health?

  • In fact, some of the panels, supposedly independent, do have conflicts now. Imagine how much worse it could get if this suggestion is followed. Furthermore, there is no chance at all that a Republican Congress is going to do anything about drug prices. Surprised that a conservative pharmacology professor would imagine that it would. And does anyone think that a privatizing, anti-regulation Congress would want to hire more FDA government employees, which by their definition are in agencies that are non-functional. Of course, not having enough employees to do the job might make an agency non-functional. In fact, the stated aim of the incoming administration and Congress is to speed up approvals. How many more bad drugs are going to hit the market?

  • Make it policy that when randomized clinical trial designs cannot adequately ensure ecological validity, that FDA consider well-established alternatives such as nonlinear dynamical models. This is especially important for post-approval modeling which can predict when significant side-effects signal trouble long before linear models can do so (e.g., agent-based models).

  • I strongly agree with all the points made in this article. And, for starters, the FDA has to have its own specialized recruiters who will directly receive all job applications and who can also directly contact and can be directly contacted by applicants. Having the qualified staff is a must in an efficiently-ran FDA, otherwise, all other changes the author suggested to improve the FDA processes will not be optimal.

Comments are closed.