How Independent is the FDA?

                Is the FDA cozy enough with the sector it oversees? opponents of the 1992 Prescription Drug User Fee Act a case may be made that pharmaceutical firms and PhRMA, its lobbying arm, have too much power because the medication review and approval process is funded by industry. 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 group, discuss these issues in excerpts from FRONTLINE’s interviews

                Since its founding in 1971, Public Citizen’s Health Research Group has been led by a director.

What steps is the pharmaceutical sector taking to influence the FDA? Where is it making an impact?

There are many different ways that the pharmaceutical sector has an impact. One of the ways they influenced FDA review was by directly funding it starting ten years ago [with the Prescription Drug User Fee Act (PDUFA)]. They did this by paying cash up front. As a result, the FDA began to view the industry as a customer rather than the general public and public health, which should be the client.

Another way the industry has influence is through the drug division’s leaders, who lack guts, spine, and a desire for controversy. These people have repeatedly asked me, “Why can’t this be settled on a scientific and medical basis?” directly. They are reluctant to confront the formidable forces of the pharmaceutical industry and many of its indentured employees in academic medicine. The leaders’ mentality is to “avoid controversy,” which entails acting in accordance with industry demands.

The lack of legislative supervision is a third way that the industry’s influence has been allowed to significantly increase. When the FDA made a mistake, like the string of errors they committed in the late 1990s, there would be a congressional hearing until 12 years ago. They would have to explain what went wrong to the legislative branch of the government. In the greatest interest of public health, they would be on the defensive in an effort to explain what went wrong.

In the Congress, nobody is present right now. In comparison to perhaps the previous 12 years with dozens and dozens of oversights, there have only been one or two days worth of oversight hearings. Thus, they escape from congressional control.

These are a few of the explanations. And “please the industry” has become the FDA’s corporate culture. Avoid a fight. Consider it part of our job to get as many drugs out as we can. …

What proof is there that the pharmaceutical industry’s influence is causing these attitudes to change in the top management positions at the FDA, that the business interests are being prioritized over the interests of the scientists?

One of the Public Health Service’s departments is the FDA. Its main goal is to increase public health. You must exercise extreme caution when it begins to move in a direction that is particularly favorable to the business due to a combination of being funded directly by the industry rather than through the U.S. Treasury and congressional pressures that are pro-industry rather than pro-consumer.

The FDA’s perceptions of the pharmaceutical sector were never more favorable than they were, at least between 1997 and 2001. They’ve been grumbling a little over the last year since there haven’t been as many medications approved. However, one simple approach to determine how receptive the FDA is to the pharmaceutical sector is to simply ask the sector what they think of the new FDA, the FDA from, say, 1995–1996 to 2000–2001. They adore it. They honored a former FDA commissioner for her outstanding performance. These things would not have existed ten to fifteen years ago, when the FDA’s relationship with industry was suitably hostile and vigilant.

It is wonderful that the FDA must collaborate with the industry. But it’s not good if the industry begins to dominate the FDA in many ways. The FDA doctors who responded to our questionnaire said that they frequently think that industry influence was working on those in positions of authority and persuading their supervisors to reverse some of the choices that they had made against authorizing a medicine.

There are several different pieces of evidence to support the claim that the pharmaceutical industry has exerted virtually unprecedented pressure on the FDA in recent years. …

What does the idea of user fees entail? How does it function?

From 1906 to 1992, the FDA’s first 86 years of operation, all of its funding came from the U.S. Treasury. In other words, everyone paid taxes, including business and individuals, and the FDA received funding from the budget.

Sadly, a law was established in 1992 that said that a significant percentage of the funding for the FDA’s work on new drug applications would come directly, in exchange for something, from the industry. They pay the FDA directly to have a medicine examined if they want it reviewed.

Because of this arrangement, the FDA and industry now have an extremely toxic relationship that is even worse than it was before, with the FDA telling the business, “We have to be kind to these people because they are paying our bills.” The government and the industry have established an unhealthy client-server relationship as a result, and I believe this has led to certain products receiving approval that they shouldn’t have and others moving more quickly than they ought to.

In my opinion, it has generally been a pretty awful idea. We are adamantly in favor of stopping this trial because during its ten years of operation, some of the worst incidents involving medication safety that we have ever witnessed occurred. That, in my opinion, is not the only explanation. However, it turns out to be a very bad idea to provide the FDA direct cash backing from the pharmaceutical business.         

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

Many detractors claim that the FDA is under considerable pressure to approve drugs and appease industry because the latter pays for the agency’s work. What are your thoughts about that?

There isn’t much pressure on us to appease the business community. The scientists and I feel very independent. We have numerous systems in place to guarantee the high caliber of the reports we use to decide whether to approve new medications. We simply deny that it has any effect on us. In reality, because to the user fee action, we’ve been able to hire a lot more people, increase the knowledge of the staff we already have, and provide them new tools. So, in our opinion, it has really aided the evaluation process.

In the event that the User Fee Act is not renewed by Congress, what happens at the Food and Drug Administration? What would occur to the staff members here?

It won’t actually happen, in my opinion. Our country’s public health infrastructure depends so heavily on our robust drug review procedure. It was recently extended for an additional five years. Simply said, I don’t believe it will take place.

Wouldn’t it make more sense, in your opinion, to have taxpayer money pay for this instead of industry?

We could explore a number of hypothetical situations, I suppose. You are aware of the constraints on the federal budget. So I’d make an effort to be true to the facts of life. Actually, we don’t really care where the money comes from when it comes to managing FDA here at the Center. Regardless of the source of the resources, we believe we can manage a high-quality independent program—as long as, of course, the resources aren’t tied to outcomes that will compromise our independence. That hasn’t been a problem at all thus far. …

He was the University of Arizona’s vice president for health sciences and a leading contender to be the FDA commissioner in 2002.   

You were a candidate for the position of Food and Drug Administration commissioner. You have some fairly solid ideas on how to make pharmaceuticals as safe and helpful as possible. … How went it?

Being a potential candidate for the Food and Drug Administration’s commissioner job made me incredibly proud. …

Unfortunately, the procedure was exceedingly difficult. Looking back on my interview and the others, it is very evident that those of us who care about medication safety have become overly divisive. The pharma industry didn’t want someone like me who would concentrate on toxicity and side effects, just as Senator Kennedy didn’t want to remove someone from the industry immediately. Thus, it became evident that I wouldn’t be able to reach a large enough constituency.

How were you informed that you couldn’t get this job by Secretary Thompson? Who said what?

I was told by Secretary Thompson that I was a candidate and that I would be very high on his list, but that it would take a while, there were other candidates to take into account, I might not be the chosen one, and it would be a while before I would know. He didn’t imply that I would face a veto; rather, he said that he would find me to be a candidate worth supporting. Today, he’s quite proud of that. He did, however, add that it wasn’t just his choice.

Did he make any hints to you that it would be a problem if you weren’t accepted by a different influential constituency?

I’ve asked the FDA to ban these supplements because I believe they are killing people and should be regulated as drugs. Some members of his staff claimed that my stance on dietary supplements, particularly those containing ephedra, had really alienated a very powerful segment of the dietary supplement industry.

It became evident that neither those who had focused on medication safety nor those who had recently left the sector could succeed. Extremely out of bounds to be accepted.

The thing that saddens me the most is that the agency cannot be regulated by people who care about food and medication safety to the point where they become involved and try to make a difference. That, in my opinion, is one of the key standards that ought to be used. Regulators must serve, of course, but they also must regulate and provide protection. For me, serving must come after protecting. You must take chances. Because people need access to food and medications, you can’t just be risk-averse and hesitant; you need to be able to weigh the pros and cons. Working in the medication development field and concentrating on drug safety causes you to identify more with the danger than the benefit.

In your opinion, is the FDA’s balance out of whack?

I believe that the FDA’s purpose is so woefully underfunded that user fees have thrown the agency out of balance. User fees allow the agency to employ individuals to work for the sector. The number of employees hired at the agency to protect, analyze data, and ensure drug safety has been drastically reduced due to the other budget, which is there for safety. More than the 17 or 20—or however many they now have—people are needed to examine the 3,000 medications that are on the market. The number of teams required to carry out medication safety is far greater than what they currently have. There is no safety net in place in our nation.

Why is the safety component being contested so fiercely? How would you describe it?

Lobbyists who demand that money be spent in particular ways set the FDA’s budget priorities. It is agreed that reviewers will be paid from the user fee. Up until recently, none of the user fees collected from the pharmaceutical industry could be applied to improving drug safety. That is changing now, though not at the rate I would like to see. Until recently, it was not possible to use some of the money for drug safety. Only because so many of us yelled that something needed to change has it changed.

What safety-related lobbying is there?

Nothing. They don’t advocate for safety. The pharmaceutical sector does not advocate for security. They advocate for quick reviews and quick market entry. No one has lobbied for drug safety; they haven’t. Consumer advocacy groups have spoken out, although not all of them in unison. Significant constituencies have not united to demand that “Stop the harm” be done. I assumed there would be action taken and the agency would receive funding to expand its safety net when the Institute of Medicine’s reports on medical errors and injury were published. But it has not taken place. There is a lot of lobbying to support the work of the agency. To assist it in achieving its safety goal, no lobbying [is] being done.       

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

The User Fee Act, or PDUFA, is what. Where did it originate?

The Prescription Drug User Fee Act was created more than ten years ago [in 1992] to offer a means of enhancing the resources at the Food and Drug Administration that are available to review pharmaceuticals. It’s a procedure that has improved the agency’s scientific knowledge and enabled prompt, efficient, and thorough reviews of prescription medications.

The pharmaceutical sector was mostly responsible for pushing for this. Give us some background information about the sector.

The pharmaceutical sector produces a lot of goods. Every year, we create a large number of new medications. The FDA lacked the resources to conduct the reviews in a timely and efficient manner, which is one of the challenges we’ve discovered. Therefore, PDUFA was a strategy to enable the Food and Drug Administration have more resources at their disposal so they could review drugs.

This action has had a significant impact. It has increased the review process’ effectiveness. The FDA has determined that the pharmaceuticals that are ultimately approved by the Food and Drug Administration are safe and effective since it hasn’t altered the standards or the review procedure. Therefore, PDUFA has done an excellent job of assisting in enhancing timely access to helpful medications. …

So, how satisfied are the pharmaceutical companies that are your members?

Because PDUFA has increased the effectiveness of the review process, the pharmaceutical sector is happy with it and has been highly supportive. The public and the pharmaceutical business both benefit when the review process is as thorough and efficient as it can be. I believe that the review process has improved significantly over the past ten years. In fact, we anticipate that the procedure will keep becoming better, and we appreciate that.

Of course, that entire system has detractors. Many people believe that Congress ought to take action in this matter. And why did Congress leave it up to business? What’s your reaction to that?

The FDA’s funding was decided by Congress. PDUFA was examined and approved by Congress three times, not just once. This is how Congress has opted to pay for the FDA’s operations. The FDA was able to complete the review process on time thanks to the industry’s support, which ultimately allowed the general public to have access to helpful medications. …

The pharmaceutical industry is interested in a strong FDA with efficient reviewers who can finish reviews quickly to help assess the risks and benefits of pharmaceuticals so that people can access medicines that are effective and safe.

Numerous employees of the Food and Drug Administration have reached out to me; some have left the organization, while others are still working there but would like to speak with you but fear for their careers. They contend that having the pharmaceutical business support the Food and Drug Administration has been for the worst, since a culture of “please the industry, approve as many products as possible” permeates the agency. What would you say to them? I’ve literally heard that from dozens of individuals. … To what do you respond?

The FDA funding plan has been examined by the Congress on numerous occasions. In order to fund the FDA effectively last year, the Congress repeatedly determined that asking the pharmaceutical sector to contribute a fraction of the necessary monies to sustain review was the appropriate course of action. The Congress has made that choice. We believe that the pharmaceutical sector has made a valuable contribution by providing the cash to assist the review. We also believe that it has contributed to the development of science.

Over the course of this time, we have learnt a great deal about how to manage and evaluate risk. We have created a wide range of new instruments to aid in tracking the efficacy and safety of medications. The system has been effective. Additionally, the FDA and the pharmaceutical sector have a strong commitment to making improvements to the system. Therefore, we anticipate that the current system will continue to advance.  

Link: https://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/independent.html