How Independent Is The FDA

Dangerous Prescription

The following is a  transcript from the Public Television series, FRONTLINE. The program, Dangerous Prescription was aired in late 2003.  I’ve kept in my files for years as a source reference documents. This past week, while working on a paper with my writing partner, Leslie C. Botha, and I opened my FRONTLINE file to review the strange twists and turns of American drug approval, regulatory process. After rereading my collection of transcripts, the information and insights struck me as being applicable in our current drug safety discussion.   I found reading the interviews was almost reading a historical journal. Its interesting to look at who’s opinion was spot on and what fears were justified,  which proved groundless and of course what issues are still hot topics.  It is a big read, take your time with it, think about it, and I hope you find it as insightful as I did.

I guess I should give the usual plug, “This transcript brought to you by, the friends and members of Public Television.”

An investigation of  America’s drug safety system…more than a dozen dangerous drugs have been pulled off the market since 1997. Why were they approved in the first place.

How Independent is the FDA?

Is the FDA too cozy with the industry it regulates? Critics of the 1992 Prescription Drug User Fee Act argue that industry funding of the drug review and approval process gives pharmaceutical companies, and their lobbying arm, PhRMA, too much influence. To address these issues, in excerpts from FRONTLINE’s interviews, are Sidney Wolfe, director of Public Citizen’s Health Research Group; Steven Galson, acting director of the FDA’s Center for Drug Evaluation and Research; Raymond Woosley, vice president of the University of Arizona’s Health Sciences Center; and John Kelly, spokesman for PhRMA, the industry’s lobbying organization.

Director of Public Citizen’s Health Research Group since its founding in 1971.

How is the pharmaceutical industry making its inroads into the FDA? Where is it exerting its influence?

The pharmaceutical industry’s influence gets exerted in a number of ways. One, starting 10 years ago [with the Prescription Drug User Fee Act (PDUFA)], the influence was exerted by their directly funding, paying cash right up front, for FDA review. So in many ways, the FDA started looking upon the industry as their client, instead of the public and the public health, which should be the client.

A second way in which the industry influence occurs is by having leaders in the drug division who are spineless and gutless, and who don’t like controversy. I have heard over and over again, directly from these people, “Why can’t this be settled on a scientific and medical basis?” They don’t like to take on the very awesome forces of the drug industry and a lot of its indentured servants, so to speak, in academic medicine. So the attitude by the leaders there [is], “avoid conflict” — and avoiding conflict means doing what the industry wants.

A third way in which the industry’s influence has been allowed to grow considerably is the absence of congressional oversight. Up until 12 years ago, whenever the FDA would make a mistake — such as the series of mistakes they’ve made in the late 1990s — there would be a congressional hearing. They would have to explain to the legislative branch of the government what went wrong. They would be — properly, and in the best public health sense — on the defensive to try and explain what went wrong.

No one is there in the Congress [now]. There have been essentially one or two days of oversight hearings in 12 years, as opposed to maybe the previous 12 years with dozens and dozens of oversights. So they’re getting away with no congressional oversight.

Those are some of the reasons. And the culture at the FDA has become, “Please the industry. Avoid conflict. Look upon our role as getting out as many drugs as possible.”

What evidence is there that it’s the pharmaceutical industry influence that is changing these attitudes in the upper levels of management at the FDA, that’s overruling the scientists, that’s putting the business interests first?

The FDA is an agency of the Public Health Service. Its primary mission is to improve the public health. You have to be very cautious when — through a combination of being funded directly by the industry, as opposed to through the U.S. Treasury, and congressional influences which are pro-industry as opposed to pro-consumer — it starts moving in a way that is very favorable to the industry.

The positive opinions of the pharmaceutical industry of the FDA have never been higher than they were at least from 1997 to 2001. The last year, they’ve been complaining a little, because there’s been a smaller number of drugs approved. But one way of gauging how favorable the FDA is acting towards the pharmaceutical industry is just to ask the pharmaceutical industry what they think of the new FDA, the FDA from, let’s say, 1995-1996 through 2000-2001. They love it. They gave a former FDA commissioner an award for doing a terrific job. You would not have seen these things 10-15 years ago, when the FDA was in an appropriately vigilant and appropriately adversarial attitude with industry.

The FDA, obviously, has to work with the industry, and that’s good. But when the FDA starts getting taken over in many ways by the industry, that’s not good. In response to the questionnaire that we sent out to the physicians at the FDA, they themselves told us that, many times, they believe that industry influence was operating on the people above them, and getting their bosses to overturn some of the decisions that they had made against approving a drug.

So there are lots of sources of evidence about the fact that the pharmaceutical industry has an almost unprecedented finger or thumb on the FDA in the last few years, compared with any time in the past.

What’s the concept [of user fees]? How does it work?

For the first 86 years of FDA’s existence, from 1906-1992, all of FDA’s funding came through the U.S. Treasury. In other words, everyone — industry, people — paid their taxes, and FDA got appropriations out of the budget.

Starting in 1992, unfortunately, a law was passed that said for a large proportion of the work done by the FDA on new drug applications, the money’s going to come directly, quid pro quo, from the industry. If they want a drug reviewed, they pay directly to the FDA to have the drug reviewed.

This system has created a very unhealthy relationship — even more unhealthy than it used to be — between the industry and the FDA, where the FDA says, “We have to be nice to these people, because they are paying our bills.” It’s developed an unhealthy sort of client relationship between the government and the industry which, I think, has resulted in some drugs getting approved that shouldn’t; drugs being put on a faster track than they should have.

I think that, in general, it’s been a very bad idea. We strongly favor ending this experiment, which has had, in the 10 years that it’s been in existence, some of the worst things happen in terms of drug safety we’ve ever seen. I think that’s not the only explanation. But direct cash funding from the pharmaceutical industry to the FDA turns out to be a very bad idea.

Acting director of the FDA’s Center for Drug Evaluation and Research.

Many critics say that having industry pay for the work that’s done at the FDA puts a lot of pressure on the agency to approve drugs and please industry. What do you have to say about that?

We don’t really feel pressure to please the industry. We feel quite independent among the scientists. We have a large number of mechanisms for assuring high quality of the reports that we do to make decisions about new drugs. We just reject that we’re actually influenced by that. In fact, what’s happened over the course of the user fee activity is we’ve been able to hire a lot more people, improve the expertise of the people that we do have, provide more tools to our employees. So we think it’s really helped the review process.

What happens at the Food and Drug Administration if Congress doesn’t renew the User Fee Act? What would happen to the employees here?

I don’t think it’s really going to happen. It’s so important to the public health infrastructure of the country that we have a good strong drug review process. We just had it reauthorized for another five years. I just don’t think it’s going to happen.

In your personal opinion, wouldn’t it make more sense to have taxpayer dollars fund this rather than have industry pay for it?

Well, there are lots of hypotheticals we could go into. You know what the federal budget pressures are. So I’d try to stick to the pragmatic reality. The reality, in terms of the management of FDA, in the Center, we’re really agnostic about where the money comes from. We think we can run a high-quality independent program, regardless of the source of the resources as long as, of course, the resources aren’t linked to performance goals that are going to interfere with our independence. So far, that hasn’t been an issue at all.

Vice President for Health Sciences at the University of Arizona, he was a top candidate to become FDA commissioner in 2002.

You were under consideration to be commissioner of the Food and Drug Administration. You’ve got pretty strong ideas about making drugs safer and as beneficial as possible. … How did it go?

I was very proud that I was considered as a candidate for the Food and Drug Administration’s commissioner position. …

Unfortunately, it was a very complicated process. … As I look back over my interview and the other interviews, it was very clear that people like myself, who care about drug safety, had become too controversial. Just like Senator Kennedy didn’t want to take somebody right out of the drug industry, the drug industry didn’t want someone like myself, who was going to focus on toxicity and side effects. So it became clear that I wasn’t going to be able to meet a broad enough constituency. …

How did Secretary Thompson tell you that you couldn’t get this job? What did he say?

Secretary Thompson told me that I was a candidate, that I would be very high on his list, but that it was going to be a long process, that there were other considerations, that I might not be the final candidate, and that it would be a long time before I would know. He didn’t say that someone was going to veto me; he did say that I was a candidate that would be acceptable to him, and now he’s very proud of that. But he also said that it wasn’t just his decision.

Did he imply to you that you would not be accepted by some other powerful constituency, that it would be a problem?

Some people on his staff indicated that my stand on dietary supplements and especially ephedra-containing supplements — I’ve asked the FDA to ban these, because I think they are killing people and they must be regulated as drugs — I think his staff told me that that had really alienated a very powerful part of the dietary supplement industry.

It became clear that anyone who had focused on drug safety couldn’t make it, just like people who had come right out of industry couldn’t make it. Too far on the extremes to be acceptable.

To me, the greatest sadness is that people who care about drug safety and food safety to the level that they get involved and they try to make a difference can’t be acceptable to regulate the agency. I think that’s one of the main criteria that should be used. Of course the regulators have to serve, but they also have to regulate and they have to protect. To me, protection is first; serve has to be second. You’ve got to take risks. You can’t just be risk-averse and unwilling, because people need medications and they need access to foods, so it’s the ability to balance risk and benefit. To work in drug development and focus on drug safety, you become identified with the risk and not the benefit.

Is the balance of the FDA out of whack, in your opinion?

I think the FDA is so grossly underfunded for its mission that it is out of balance because of user fees. User fees enable the agency to hire people to work for the industry. The other budget has been so limited and so cut — the other budget being that which is there for safety — the number of people hired at the agency to protect, to analyze data and drug safety, is criminal. The number of people required to study 3,000 drugs that are on the market is far more than the 17 or 20 — however many they have now. The teams that are needed to do drug safety are infinitely more than what they’ve got right now. We don’t have a safety system in this country.

Why is the safety part resisted so adamantly? How do you explain it?

The budgets of the FDA are determined by lobbyists who call for money to be spent in certain ways. The user fee is negotiated to be spent on reviewers. Until recently, none of the money that was sent by the pharmaceutical industry for user fees could be used for drug safety. Now that’s changing — not to the rate I’d like to see it. Some of the money can now be spent for drug safety, but that was impossible until recently. It’s only because many of us have screamed that that has to change has it changed. …

What’s the lobbying in terms of safety?

Nothing. They’re not lobbying for safety. … The pharmaceutical industry doesn’t lobby for safety. They lobby for rapid review, rapid access to the marketplace. They haven’t lobbied for drug safety; no one has. There are groups, consumer groups, that have spoken out, but not with a uniform voice. Large constituencies haven’t joined together to say, “Stop the harm.” When the papers came out from the Institute of Medicine talking about medical errors and medical harm, I thought surely there would be action taken and the agency would be given money to increase its safety net. But it hasn’t happened. There’s a lot of lobbying for helping the agency serve. … No lobbying [is] being done to help it get its safety mission accomplished.

Spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA), the industry’s lobbying organization.

What is PDUFA, or the User Fee Act? Where did it come from?

The Prescription Drug User Fee Act was established over a decade ago [in 1992] to provide a way to help improve the availability of resources at the Food and Drug Administration to review pharmaceuticals. It’s a process which has worked very, very well in increasing the scientific expertise within the agency to allow timely, effective, and thorough review of prescription drugs.

This is something that was largely pushed by the pharmaceutical industry. Give us some history from the industry’s perspective.

The pharmaceutical industry is remarkably productive. We develop a number of new medicines every year. Part of the challenge that we’ve found was occurring a number of years ago — that the FDA didn’t have the resources to do the reviews in a timely and effective way. So PDUFA was a way to help improve the resources available to the Food and Drug Administration so they could review pharmaceuticals.

This act has been very effective. It has improved the efficiency of the review process. It has not changed the standards or the review process, so the drugs that are ultimately approved by the Food and Drug Administration are determined by the FDA to be safe and effective. So PDUFA has worked very, very well in helping to improve timely access to beneficial medicines. …

So are your member companies, the pharmaceutical companies, happy?

The pharmaceutical industry has been pleased with PDUFA and has been very supportive, because what it has done is to improve the efficiency of the review process. It’s in the pharmaceutical industry’s interest and in the public’s interest to have that review process as thorough and effective as it can be. I think that we have made tremendous progress during the last decade in improving the review process. In fact, we expect that the process will continue to improve, and we welcome that.

Of course, there are critics of that whole system. There are lots of people who say, “Congress should do something about this. And why has Congress left it to industry?” How do you respond to that?

Congress decided how to fund the FDA. Congress reviewed and passed PDUFA — not once, not twice, but three times. Congress has decided this is the way it wants to fund the activities of the FDA. Industry has been supportive, because what this has done has been to allow the FDA to complete the review process in a timely way, and ultimately to allow the public to have access to beneficial medicines. …

What the pharmaceutical industry is interested in is having a strong FDA, with effective reviewers who can complete reviews in a timely way to help assess the benefits and the risk of pharmaceuticals, so that medicines that work and that are safe can be available to the public. …

I’ve heard from a lot of people inside the Food and Drug Administration — some people who’ve quit, some people who are still there and would like to talk, but their jobs are threatened. They say that having the industry fund the Food and Drug Administration [has been] for the worst, that there’s an atmosphere there [that says, “Please the industry, approve as many drugs as possible”]. What do you say to these people? I’ve heard it from dozens of people, literally. … What do you say to them?

The Congress has repeatedly looked at how it wants to fund the FDA. So once, twice, and again, last year, the Congress decided that the best way to fund the FDA was to look to the pharmaceutical industry to provide a portion of the funds to help support review. That’s the decision of the Congress. The pharmaceutical industry has contributed the funds to support the review, because we think that has been an effective approach. We also think that it’s been a way of helping to advance science.

We have learned over the course of this time a tremendous amount about how to monitor risk, how to assess risk. We’ve developed a wide variety of new tools to help monitor the safety and effectiveness of pharmaceuticals. The system’s been working. There is also a very strong commitment on the part of the FDA, as well as on the pharmaceutical industry, to improve the system. So we look forward to the continued progress in the system that we have in place today.