Some Things that Some People Might Want to Know about the FDA

I’m an FDA – Food and Drug Administration – scientist. I am not alone in being very upset about many things that have occurred at the FDA in recent years. An article that describes a poll of FDA scientists conducted by The Union of Concerned Scientists (UCS) and Public Employees for Environmental Responsibility (PEER) last year sums up the way I feel about things at the FDA:


I have previously written and posted articles critical of the FDA on DU. Those articles have dealt with: The FDA’s preference for industry representatives over the public with respect to meeting invitations; George Bush’s war against science and our Civil Service system; and, the time that a scientific article of mine was pulled by the FDA Commissioner just before it was due to be published in a medical journal and just after the Commissioner had met with representatives of the corporation that manufactured the medical device that was the subject of my article.

Recent frustrations have caused in me the desire to share some things with my friends at DU, as I am very interested to see if other people see this similarly to the way that I see it. I’ll try to be as objective as I can about this.


A little background

I work for the part of FDA that evaluates and approves medical devices for use in humans. It’s called the Center for Devices and Radiological Health (CDRH). Two main components of that Center are the part that approves the medical devices and the part that evaluates their performance in humans after they’ve been approved and marketed, in order to see how they perform in “the real world”, as we say.

I work for the latter part of CDRH – the part that evaluates the devices after approval and marketing (call us “post-market”). The other part (call them “pre-market”) until recently was about ten times larger than we are – they had about a thousand employees, to our 100.

One very big difference between us and them is that almost all of our scientists have training and degrees in public health, whereas almost none of their scientists have that. It makes a big difference in one’s outlook. Public health professionals are trained to have an attitude that says that they work to serve the public. I believe that it is fair to say that, in contrast to us, most of the pre-market scientists in our center feel like they are supposed to serve the corporations that make the medical devices more than they are supposed to serve the public.


A transition to more post-market emphasis

In the last couple of years there has been a move to give us public health scientists on the post-market side of the Center more authority over post-market issues. Until very recently, the pre-market people not only had all the authority over approving medical devices, but they had authority over the post-market evaluation of the devices as well. We post-market people merely served as their consultants. We would evaluate the scientific data and make recommendations based on our public health expertise. And all too frequently our advice would be met with comments like “But that’s not fair to the manufacturer”. Why not? Because neither manufacturer A nor manufacturer B ever had do those things, so why should we require manufacturer C, for example, to conduct a study to better evaluate the safety of their product?

We always felt that having the pre-market approvers of the medical devices also be responsible for the post-market evaluation of the devices was a very bad idea. First of all, lacking public health degrees, hardly any of them had proper training for developing and overseeing post-market scientific studies. Secondly, there was a serious conflict of interest involved. Having approved a medical device, they would be very reluctant to find fault with it after it was marketed because that could be seen as admitting a serious mistake. It’s a little bit like giving the President of the United States the authority to give pardons to his own staff for crimes they may have committed. Indeed, the pre-market folks routinely exhibited much less enthusiasm for the post-market evaluation of devices than they did for the approval of the devices that they oversaw. And on many occasions when we would try to discuss with them problems with the post-market performance of a device that they had approved, they would react very defensively.

So we pushed to get more authority over the post-market evaluation of medical devices, and finally a major transition began to take place, giving us that authority. I want to believe that this transition is largely attributable to our efforts towards it, but I am unable to say for sure exactly how it happened. However, the transition is by no means yet complete, and we are still struggling for it.


An example of how the FDA makes decisions regarding post-market evaluation of medical devices

Now I come to the part that I really wanted to talk about – how decisions have been and continue to be made regarding various aspects of post-market studies to evaluate medical devices.

Recognizing that only a small minority of persons who read this post are statisticians or have significant statistical training, I’ll leave statistics out of this and try to explain it in simple English:

In considering how to design a post-market study, one of the main considerations is to decide on where to set the bar for the post-market performance of the medical device with respect to its safety and its effectiveness. More specifically, where do we want to set that bar in comparison to alternative means of treating the disease or condition that the medical device is supposed to treat? Do we want to say that it’s ok to be 10% less safe and effective than currently available treatments? 20% less safe and effective? 50%? This is a complex clinical/scientific issue, and I don’t intend here to discuss all of the many considerations that should go into such a determination. What I will do here is tell you how the pre-market folks routinely make that determination.

Here’s how they do it: First they decide, perhaps after talking with the manufacturer, how many study subjects the manufacturer would consider acceptable for including in the study. If the number is too high, the manufacturer will say that the study would be too costly or too “burdensome” for them. So, in that manner, the pre-market folks determine the number of subjects who will participate in the study.

The second step is to create scientific justification for the sample size that they determined. They do this by asking us – the post-market folks – to tell them what margin of safety or effectiveness will statistically justify their pre-selected sample size. The lower the bar, the fewer subjects they need in their study. So, their plan is simply to pick a low enough bar that they will be able to justify their pre-selected sample size.

Get it? It’s kind of like deciding that global warming doesn’t exist, and then picking the scientists who will support your conclusion – if you can find them. Or, like deciding that weapons of mass destruction do exist, and then finding the evidence to support that. It’s very simple, really.


The struggle for control

Recall I said that in the past the role of us post-market folks was merely to advise the pre-market folks on how to set up their post-market studies. I would never play along with their games. I would simply tell them that it was not appropriate to pre-select the sample size or determine the performance bar based on the need for a small sample size. They would say “Thank you very much”, and that was often be the last I would hear from them.

But now, as I said, we are attempting to gain control over the process. And just a couple days ago we began a confrontation over this issue, while it is still unclear which side is going to get to decide the matter. Next week we have a meeting to try to settle this, so wish me luck.


Viewing this in perspective

They’re not all like that. Many of them appreciate our input. And many of them appreciate our input even though they can’t even begin to understand our point of view. Most of them are good people, in my opinion. But they have worked in a specific culture for so long that they have imbibed the values of that culture, and they view almost everything through the eyes of that culture. In short, many of them don’t have the slightest clue that the FDA is supposed to be a public health agency; that the public deserves at least as much consideration as do the corporations who make the products they deal with; or that there is anything wrong with making scientific decisions based on the needs of corporations.

I’m sorry that I can’t tell you when or how this all started. I came to the FDA in 1999, and it was bad then, although I would say it got quite a bit worse during the Bush pResidency. True, in 1999 we had a Democratic President, but we had also had a Republican Congress for quite a few years by then. And this was followed, starting in 2001, with almost six uninterrupted years of a lethal combination of Republican Congress and pResident at the same time.

It’s not just the FDA, of course. All federal government agencies have been badly corrupted during the years of the Bush pResidency. In a democracy, money is not supposed to drive the most important decisions that a nation makes – but that’s the current status of our nation; in a democracy, people are supposed to have some confidence that their votes will be counted – but that’s not the current status of our nation; in a democracy, the news that people get is not supposed to be dominated by a handful of wealthy and powerful corporations – but that is the current status of our nation; and last but not least, in a democracy that also has a strong mechanism built into its Constitution for getting rid of incompetent and corrupt public officials, a pResident with a 27% approval rating would be out on his ear before too long – but that’s not the current status of our nation.

I'm guessing your in White Oak. My wife is applying over there because it looked like they were increasing staff. She's currently on an NCI contract and the cuts there are hurting her.
Have you seen any postive changes since the last election?

As I noted in the OP, there has been a major transformation recently to give us post-market people control over the post-market evaluations -- something that should have happened a long time ago. If this works out as planned, it will be a major change in a very progressive direction -- to have the post-market evaluations finally under the authority of a group of scientists with public health training and public health attitudes.

I said in the OP that I couldn't explain how it happened, and that I hoped that it had something to do with our efforts to make it happen. For some reason I hadn't even thought about the possibility, as you mention, that it is because of the change of control of Congress. How dumb of me not to consider that! So, maybe that's the answer, and hopefully we'll continue to see changes in a positive direction after the next election, which will hopefully gain the Dems even a bigger share of Congress, and the presidency too.

I work in Rockville, at the Piccard building. They're talking about moving us to White Oak in 08, but they've been talking about that for a very long time. Maybe 09.

Good luck to your wife, I'd be happy to talk with her about it if she's interested.

run the country, you get rampant incompetence and corruption.

Who ever is elected in '08 will have one huge re-building project to tackle. It appears we should be in for a major landslide, but wait that happened in '04 and we still got stuck w this bozo. Not much has changed, although awareness is much more prevalent. I still intend to ask candidate how they would respond publicly if they lost an election shadowed in suspicion.

Another winner TFC! Interesting background.

I believe that things have changed somewhat. I believe that there was a lot more vigilance on Election Day 2006 than there was in 2004, and I believe that it paid off. I worked as a poll watcher on Election Day, and I was part of a massive system of poll watchers. I kept in close contact with the organization (Poll Watchers for Democracy) that was running the program, and they were ready. I reported an irregularity to them, and they had lawyers all over it immediately. They would have taken it to the limit had Dems lost any of the major races in Maryland. I talk more about it in this post:
http://www.democraticunderground.com/discuss/duboard.php?az=view_all&address=364x2859666

So, in sum, yes there was a good deal of election fraud in 2006, but we were ready for them and probably prevented it from being a lot worse than it could have been. I feel confident that there will also be much vigilance in 2006.

K and R. Thank you for this post.

I am very sad that someone like you has had these experiences.

The independent scientists are becoming extinct - the current culture of corruption just will not allow people with ethics to flourish.

And in another decade or so, the narrowing of judgement will be so overswhelming that younger scientists will not even know that at one time there was a real science behind the erected structures.

The corrupted structures will have become so "normal' that the ability to evaluate will be lost perhaps forever. (in this country - perhaps in other countries science still has a chance.)

See www.coastalpost.com/02/07/05.htm

It's a very good sign that Bush's approval numbers are in the 20s, while Cheney's are in the teens. It's a good sign that people are sick and tired of the Republican Party and are leaving it in droves. It's a good sign that a poll of FDA scientists shows that many of them are mad as hell, rather than just inclined to go along. I think we've got a good chance, but it's hard to know how we're going to take our country back. Some people think that Bush might cancel the 08 elections. There's going to be hell to pay if that happens.

Wow, that article about the NEJM sure is scary. I wonder what's behind it -- whether it's because they've been taken over by new management, or what.

Thank you for your concern.

Thanks for the links, I hadn't seen your other posts.

Or too dated?

I am not sure why the problem with sample sizes. Is the corporation paying for the study? Who does the study - you or some independent research firm? If there are contraindications with a device then people will goto their doctors and then wouldn't that information be in various insurance company databases?

Aren't sample sizes for accurate measurement given by mathematics?

I don't understand some of your other questions. Why would anybody wanna market something that is less safe and effective? Why would anybody buy it? Doesn't it need to be more of one or the other in order to sell? Either more effective, or safer, or maybe just cheaper. That's a trickier trade-off. How much safety do you give up for more effectiveness? How much is even known about long-term safety?

First, I need to say something about the practice of medicine in general. With the practice of medicine in general, as with medical devices, the public, and the medical community as well, is often ignorant of what is most safe and effective. That is the main reason why the FDA was created. If the safety and effectiveness of medical treatments were widely and universally known, there would be no need for an FDA to evaluate and approve them. The FDA exists mainly to inform the public and the medical community about the safety and effectiveness of drugs, foods, biologicals and medical devices. If something is not sufficiently safe and effective it is supposed to be disapproved for market, so that it will not have the potential to hurt people.

That is why drug companies and device companies spend millions of dollars in advertising, sponsoring conferences, etc. To put their spin on the value of their product.

Yes, sample sizes are given by mathematics -- and that is my point. But various assumptions have to be plugged into the mathematics. If we say that it is acceptable to have a device that causes twice as many deaths as existing alternatives, then the calculated sample size will be considerably less than if we only allow 10% more deaths. The smaller the sample size, the less costly for the company, and the less certainty in the data. That is what many corporations want.

Yes, the manufacturer pays for the studies.

I haven't read the book you refer to, and I don't know anything about it.

Finally, if the safety of a device (or drug) was so obvious, why would a major corporation go to so much trouble to suppress the scientific article that I wrote about their product. My article was accepted for publication in the most widely read (by vascular surgeons) vascular surgery journal, so it was peer reviewed by experts in the field. My article was about ruptured aortic aneurysms caused by their device -- a highly fatal event. Fortunately, someone leaked the story to the Wall Street Journal, which published the it on its front page. You can read about it here:
http://irbforum.com/forum/read/2/79/79Vt?PHPSESSID=e21c5eaf53fbfc93d40e686f52a9b7a4

Mind-numbing.

We still have a civil service system, though Bush has done whatever he can to destroy it. And I'm also fortunate enough to be protected by my own management chain.

I feel that if I just went along with these people my soul would begin to shrivel up and die.

for sharing this with us. Sounds like a constant tug of war?
K&R

But we've made progress, and I'm hopeful that we will prevail. Slowly, but prevail nonetheless.

And I just saw a supportive e-mail from my boss this morning, ending with "Let's stay on top of this!!!"

Yes, I see it the way you do. The post-market people should be in control of the entire post-market evaluation process.

Good luck in your meetings next week, and thank you for your public service. :patriot:

It looks like my management chain is going to support me on this -- I just saw a supportive e-mail from my boss this morning, ending with "Let's stay on top of this!!!"

Best of luck to you and your cohorts who are standing up against the reverse-engineering of the safety testing process.

Next week should be very interesting.

that helps keep these fuckers in check.
If they had their way they would gut the whole thing
and let the Market decide.

Having the "market" take care of something like this is ridiculous. In order for the market to work, people need information. That information is obtained through scientific studies. Without them the market is blind.

against the strangle hold that business has on the federal government under the Bush administration.

I do not know if you have any way to know about this, but I have been concerned that the FDA has been banning old, grandfathered remedies in a deliberate attempt to boost the sales of patent drugs sold by various pharmaceutical companies, specifically Glaxo-Smith-Kline. For example, quinine, which a number of my elderly patient had used for years for leg cramps back when I was in private practice suddenly got yanked from the shelves at the same time that GSK was doing a big direct to the public marketing campaign for Requip. And all but one ergot containing migraine headache remedies were banned at the same time that GSK was doing a direct to public marketing campaign of its much more expensive migraine headache medication.

Odd coincidences like this---it really looked like the FDA was creating business for GSK or at the very least had coordinated with GSK, giving them a heads up to start an ad campaign, produce their ads, buy the ad time and start running the ads right before the bans were announced---make the FDA look like the errand boys of the drug industry.

And then we discover that the FDA knew a year ago about the cardiac concerns with Avandia, but did not think that they were worth pursuing. The cardiac problems with Avandia are at least as worrisome as the reasons they cited for banning quinine and all but one ergot, IMO. Quinine and ergot were yanked from the shelves because they had been implicated in a handful of cardiac deaths and there were safer alternatives available. Avandia has been implicated in cardiac deaths and there are safer alternatives available. The only difference I can see between the two cases is the Idiocracy (from the movie) difference. If we stop watering the crops with Brando, the Brando Company will lose money, so we must continue to use Brando/Avandia for the health of the economy. However ergot and quinine are cheap generics that make no big drug company any money. Indeed, they save a lot of consumers a lot of money that they should be spending on Requip and Imitrex instead.

I work with medical devices, not drugs, so I wouldn't know too much about the issue you speak of.

But I have a very distinct impression that the FDA is very corrupt these days.

Here's a couple of excerpts from another post of mine where I talk about several scandals:

I was in a similar situation at NIH, where they were so dogmatic about the appearances and doing it the way it was always done, when I was brought in to establish new protocols I was put into a nasty political situation. And I too had the support of management (or the co-chair of the department and chief administrator) until the higher ups got rid of the big obstacle, my boss the former co-chair and thus it was open warfare on me and my methodologies. It sounds like there are parallels to your situation.
I now have a very bad opinion of NIH because of it. Your post really did remind me of my situation.

So, what happened to you over that?

My ex-boss (whom I have not talked to for months now) is leaving for a job either in Europe or his native Australia since his career is ruined here.
He was pushed out in October of last year. It became vicious and personal on me to the point where I left in December with no other job lined up because they were making my life miserable (deliberately). I believe I am black listed at NIH, because I can't even get an interview there and there were signs that multiple people were very interested in qualifications. My name and my former bosses names are both mud in NIAID. I believe the person who heads up that institute (whom I have read disturbing things about) has it in for me.
I am about to start a good job at a company that has no big NIH contracts (which I think was hurting me as well) so FINALLY I might be able to put this whole affair behind me. I can't talk to my coworkers (the good ones) anymore, its still too painful.

It’s not just the FDA, of course. All federal government agencies have been badly corrupted during the years of the Bush pResidency. In a democracy, money is not supposed to drive the most important decisions that a nation makes – but that’s the current status of our nation; in a democracy, people are supposed to have some confidence that their votes will be counted – but that’s not the current status of our nation; in a democracy, the news that people get is not supposed to be dominated by a handful of wealthy and powerful corporations – but that is the current status of our nation; and last but not least, in a democracy that also has a strong mechanism built into its Constitution for getting rid of incompetent and corrupt public officials, a pResident with a 27% approval rating would be out on his ear before too long – but that’s not the current status of our nation. :grr:

God help us - Will GWB take over before the 2008 election is finalized? We will soon find out!

A number of people have considered that possibility:

http://www.democraticunderground.com/discuss/duboard.php?az=show_topic&forum=364&topic_id=1804660

not for the FDA, though some of my friends are. I've served on other scientific review boards.

I'm also very active politically with my local Democratic Party. I've spoken at candidate's forums and scientific meetings. I spoke to a group of scientists and clinicians at a citywide forum in 2000 and 2004 about the need to elect Democrats to the WH and Congress to protect the integrity of our federal government's process of scientific research and review. We asked scientists to get involved and educate each other and the public about the need to elect leaders who would support you.

Few in your community really believed the dangers the Bush administration posed. They insisted Bush would never politicize science and research, no president had ever done such a thing. They were more concerned about protecting grant funding and implementing tort reform. They were easily sidetracked by GOP talking points.

All I can say is, we tried. We tried to convince you these things you thought wouldn't happen could.

As they say, failure is a good teacher. We've all learned the hard way. Is the research community ready to listen now? I hope so, because we need your community to become more active and involved, to speak out.

...gave the FDA the teeth it needed to keep the US food and drug supply reasonably safe for over half a century, since exactly the same scenario is recurring today.

Di-fucking-ethylene glycol in products intended to be ingested (or that might potentially be ingested) by people and other critters.


Also, (I'm shaking my head here, at policy, not you) could you please explain under exactly what circumstances the FDA might approve of a treatment that is twice as lethal as existing treatments.

I can see where some/many might chose a significantly increased quality of life at the expense of a few years chopped off the end.

But to double ones risk, for no apparent gain is not a decision that any right minded person would chose to make, and one that would piss me off no end, if some penny pinching bureaucrat made it on my behalf, to either save a few dollars or to ensure that those dollars ended up in the right pockets.

I work at a clinic, and I'm thinking who would benefit from changing the many years old acceptance of opened medications lasting for 90 days, now are good for 28 days? Maybe the pharmaceutical companies? Makes me wonder if the FDA isn't in the pockets of these companies.