dangerous prescription
homethe fdainterviewsdiscussion
interview: john kelly, m.d., ph. d.

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.

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.

Give me a little bit of the history of PDUFA, the Prescription Drug User Fee Act. I don't understand. 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.

photo of kelly

John Kelly is senior vice president for scientific and regulatory affairs and a spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA), the industry's lobbying organization. He tells FRONTLINE that the industry is pleased with the way user fees, introduced under the 1992 Prescription Drug User Fee Act (PDUFA), have made the drug review and approval process more efficient, and notes that Congress has decided that user fees are the best way to fund this part of the FDA's activities. This interview was conducted on Feb. 12, 2003.

How has the review time actually changed at the Food and Drug Administration, from before PDUFA to today, which is 11 years into it now?

As a result of the improved resources at the Food and Drug Administration, review times now average about a year and a half for medicines. That's a significant improvement from where we were about 10 years ago.

You're averaging about a year and a half. So is the FDA incorrect when they say they're down to six months or less for those reviews that are expedited by a user fee? Is that how it works?

The FDA review process is thorough and extensive, to assure that the medicines that are available to the public are safe and effective. That's what the FDA does, and that's what the pharmaceutical industry provides information to the FDA to help them accomplish this. PDUFA has provided resources to help support this process, so that we have a timely and effective review process.

The length of time it takes to review medicines varies. Some medicines are reviewed quickly. Some take a long time, because of the complexity of the development process, and because of the tremendous amount of data that companies develop and analyze to help assess the safety and effectiveness of 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.

Would the industry have any objection if Congress said, "Well, let's take a step back. Why don't we do -- this?"

Congress has decided to fund the FDA through user fees. It's a process which has been in place for a number of years. It's a process that has worked. Congress has repeatedly reviewed this, and continued this approach. We expect that Congress will continue this approach.

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.

How did the industry take to the idea of extending the use of the money [to monitoring drugs after they've gone on the market]?

The pharmaceutical industry has been very strongly supportive of trying to improve risk assessment and risk management. Risk assessment is an integral part of the entire drug development process. From the time that a drug is first discovered and evaluated and tested, at every stage, risk is evaluated. So continuing to monitor risk after a drug is available to the public is part of what the industry has been doing for a long time, and has been strongly supportive of continuing.

Whether it's true or not ... [one] theme that seems to come out again and again in all of the stories [we've looked at] is a reluctance on the part of companies to deal with bad news. There's lots of good news about pharmaceuticals. But it seems like when there's bad news, [if] it looks like something's not working out, there's a great reluctance to focus on it. How does the pharmaceutical industry deal with bad news? Is it willing to accept bad news?

No medicine is risk-free. In developing medicines, assessment of risk, evaluation of risk, and management of risk is central to the entire pharmaceutical process. It's also central to the practice of medicine and healthcare. So as new information becomes available during the drug development process, during the approval process, and also after a medicine is available to patients, monitoring the safety of a medicine is a critical part of what we do.

As new information becomes available, then that information is studied and evaluated. If any kind of changes or adjustments need to be made, then that information is shared in whatever is the most appropriate way. So pharmaceutical companies have been doing this as a central part of their business. We share this information once it's evaluated and established with physicians and with the public.

I guess that's sometimes what becomes the point of contention. It certainly becomes the point of contention when there are lawsuits. At what point does a company have to share with the wider world their own investigation of what may be a problem? How appropriate is it to continue to study a problem when it's staring you in the face?

No medicine is risk-free. Pharmaceutical companies work very hard, the scientists, the physicians in the companies, as well as the physicians who are practicing in caring for patients--

Can you shed some light on what seems to be a move to study the problem more rather than to take action?

No medicine is risk-free. Scientists and physicians within pharmaceutical companies, as well as physicians who provide medicines or prescribe medicines for their patients, monitor the effect of pharmaceuticals very, very carefully. As information becomes available, it's essential to study it carefully, to study it fully, and then to determine what kinds of recommendation should be developed. That's what the pharmaceutical industry does. That's what the FDA does. That's what physician organizations do. And it's ultimately what forms the basis for the advice which is given as to when the risk of a particular medicine might outbalance or outweigh the benefits, or when changes need to be made.

When there are questions about whether the risk or benefit is on the right side, what side do you err on?

Every patient is different. Their medical needs vary. What is best for one patient might be different than what's best for another patient. Also, many patients, in fact, because of their unique needs, are taking multiple medicines. So what is critical is for the patient and their physician to determine what's the best approach for them. In some instances, the approach that one patient would take might be quite different than the approach that another patient would take.

Balancing benefit and risk is a central part of how medicine is practiced. It has to be individualized. It's done one patient at a time with their physician.

Maybe you can shed some light on this. ... Why is it, in the United States, that doctors seem to, when they have adverse events that occur, why would they report them overwhelmingly to pharmaceutical companies rather than reporting them to the FDA? Can you shed some light on that?

Well, every day in this country, millions of Americans are taking medicines that benefit them, that help them lead better lives, that help them manage particular health conditions. With so many different patients taking so many medicines that benefit them, we learn more information about the safety profile of particular medicines. If there is a concern that emerges, physicians have a variety of ways in which they might share that information. They can share it directly with the pharmaceutical company. They can share it with the FDA.

So it's taking that information and then evaluating it that helps us to learn more about how a particular medicine works, if there are risks, [and] to then evaluate them. What we find is that, in some instances, those individual case reports help us learn risks that we may not have known much about before, or that we now understand in a better way. It's also possible that what we find is that the medicine perhaps wasn't being taken properly; maybe it was being taken with another medicine which shouldn't have been taken.

In some instances, what we find is patients aren't taking medicines the way their physicians recommend them. They're taking them too often, or they're taking them in the wrong dose, or perhaps for the wrong condition. It's very important to study this carefully, so that we can provide the right kind of information to physicians and patients.

...What I'm trying to understand is -- and no one's been able to explain this to me -- the Food and Drug Administration said to me that 90 percent of their adverse event reports come from pharmaceutical companies. They don't come from doctors or from hospitals or pharmacists or nurses or consumers. They come from the pharmaceutical companies. ... What I'm trying to understand is, why does it go through the pharmaceutical companies? Do you understand why that's the way it works in this country? No one says that's the way it has to work. There's no rule that says doctors have to report to pharmaceutical companies, and not report to the FDA. But why do they?

We have a very effective mechanism for sharing information between physicians and pharmaceutical companies. The pharmaceutical companies who have developed a medicine, who have studied it for 10-15 years before it was even approved, oftentimes understand that medicine better than anyone else. So [the companies are in the best position] to evaluate information about some potential finding, to analyze it, and to see whether, in fact, this is new information, or information that we already had available to us.

Pharmaceutical companies are committed to this. It's part of what they do. In the long run, it's the key to the way in which we develop new information that we can provide to physicians and patients about the best way to use a particular medicine.

You're not quite answering my question. Do you understand why it is that doctors tend not to report to the Food and Drug Administration, but tend to report to the pharmaceutical companies? It seems like a backwards way to do it -- that's all. If you want a government agency to be monitoring, you'd think that they would be encouraging people to report directly to them.

I think that we have a very effective system. I think that the system has improved over the years. We are now looking at even better ways to help monitor risk, to evaluate risks. That's part of what the new PDUFA legislation was designed to accomplish, which is to help identify potential new ways to monitor risk, so that we'd get the information that we need, that we evaluate it thoroughly, and then ultimately provide the kind of useful information that physicians and patients need.

[Because adverse event reporting is] a spontaneous and voluntary system, the FDA is arguing about whether they're looking at 1 percent or 10 percent or 50 percent of what's actually going on out there. ... The argument will occur inside companies, too. They don't know what they're looking at. I've heard this everywhere. ... "We see a number of adverse event reports, but we don't know out of how many patients that is. We don't know whether we're looking at the whole pie, or this slice of it."... So if industry were asked for suggestions on improving the system, what would industry suggest? Or is everything just fine?

Evaluating the risks -- the benefit and the risks of pharmaceuticals -- is challenging. The scientists and physicians who work within pharmaceutical companies have been evaluating the risks of pharmaceuticals for a long time. This is a scientific process in which we need to look at data in a careful, thoughtful, and effective way. It's part of what's central to the drug development process, deciding whether a particular medicine, in fact, is ultimately safe to use in patients, and for what purposes.

The pharmaceutical industry has been very strongly supportive of finding new tools, new ways to monitor risk. It's critical to what we do. That's why the pharmaceutical industry was so strongly supportive of the FDA expanding its capability in this area. We've been working closely with the scientists at the FDA to try to look at new ways to help collect information, to evaluate that information, and then to use it to get a better understanding of how medicines work and what kind of information we should share with physicians and the public about the medicines that they're using and prescribing.

The specific question I was asking was, it seems like a lot of the drugs that ultimately got taken off the market involved a lot of discussion. ... It seems like a lot of the debates that are going on have to do with the reliability of [the data]. They don't know what they're looking at. ... This is exactly what happened with Baycol. ... They sat around arguing about whether their data was reliable. This was FDA data. Did it mean anything because it was coming from this spontaneous adverse event reporting system that could be affected by all kinds of variables ... and it was hard to compare one drug to another? Ultimately, it ended up being an excuse for not taking action, for embarking on another study, because the data wasn't convincing. ... What can we do to make it better? What would industry suggest to make it better?

Industry has been working with the FDA and working with clinicians and scientists around the globe to try to look at better ways to monitor the safety and the effectiveness of pharmaceuticals. What we have been trying and developing are a variety of tests and approaches and strategies that we use during the drug development process to decide whether a particular medicine might work or might not, and then, also, to monitor medicines after they're in use.

This is a scientific process in which collecting data, analyzing data, and ultimately making decisions based upon the data is critical to decisions about what medicines should be available to the public, how they should be used and, if there needs to be restrictions on the use, what those restrictions should be.

What we have to make sure that we do here is that as we try to balance benefit and risk, what we don't do is to deny access to beneficial medicines to patients that can help them manage health conditions that medicines are critical to help manage. So this is a scientific process. The data need to be evaluated in a careful, thorough way. That's how we will make progress. The pharmaceutical industry, with the scientists and the physicians who work within this industry, as well as practicing physicians around the globe, are committed to this -- which is to collect information, to evaluate it -- to help us develop better medicines that can help care for our patients.

... Does the industry here have a position on mandatory reporting [by physicians] to the FDA, versus having a voluntary system?

The pharmaceutical industry is very strongly supportive of ways to help improve risk assessment and risk management approaches. We think it's in the best interest of the public. As far as some suggestions about mandatory reporting, there's no proof that that will work. In fact, what we see is that that might just increase the information and obscure potentially useful information. So we are in the process of studying this, as well as many other proposals, to try to see some of the ways we can help improve the effectiveness of our monitoring systems. The pharmaceutical industry is committed to working very closely with the FDA to try to help find better ways to monitor risk, and ultimately to help manage risk.

Why would mandatory reporting confuse the issue, as opposed to help clarify it?

There are many instances where mandatory reporting just adds new burdens to the healthcare system without bringing any significant benefit. So we're not sure, at this point, that that's going to ultimately be proven to be effective. On the other hand, we're evaluating this approach, as well as many other approaches, to try to see what are some of the effective ways we can help improve risk assessment, risk monitoring and, ultimately, risk management.

You said mandatory reporting would [confuse the issue]. But why could it, and why would it confuse the issue, as opposed to shed light on whether a drug is safe or not?

There's no evidence to date which has shown that mandatory reporting would help improve the effectiveness of the monitoring of pharmaceuticals. What really needs to occur here is we need to continue to try to find better ways to help evaluate the data that we have available to us to try to help assess -- when medicines work, and what some of the limitations on medicine should be.

That's really where the efforts today are focused, which is trying to help identify better tools, better approaches to collect data, and then, really, to evaluate the data. This is a scientific process. It's a medical process, in which we need to look at available information in as responsible and effective way as possible to try to evaluate medicine. ...

We talked about PDUFA [and user fees and that the industry is] happy with the way that's going. 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.

Anything else you'd like to say about this topic? ...

The pharmaceutical industry is committed to developing better ways to monitor the safety and effectiveness of the medicines that we provide to the public. We think that we have been effective in producing many safe and effective medicines, and also in helping to collect information about the safety of those medicines. It's through that kind of effort that we think the public can be assured that we will continue to make available the best medicines that we possibly can. Once those medicines are available, the key is that they be used properly, that patients understand how best to use them, and that patients follow the recommendations. That's ultimately the key to this -- that patients use medicines for the right reasons and in the right way.

Successful use of medications depends upon an effective relationship between physicians and their patients. That's really the key. ...

The process for developing medicines is a remarkably thorough process. What we have been able to do is to make available to the public thousands of medicines over the course of the last 20 or 30 years that bring tremendous benefit to patients. After a medicine is approved and more patients take it, we learn additional information about a particular medicine, so rare events or infrequent events might appear.

But what I think you should also be aware that, during the period from 1970 to 1990, before PDUFA, the frequency of drug recalls was no less and no greater than the frequency of drug recalls during the PDUFA era. So what we have been successful in doing is improving the efficiency of the review process. But the standards of the review process have not changed. Safety remains the primary focus of the Food and Drug Administration. We expect that it will continue to be, as it should be.


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posted november 13, 2003

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