Pharm Exec Q&A: Inside View

AS IF FDA DIDN'T FACE ENOUGH TOUGH CRITICISM last summer: The Union of Concerned Scientists (UCS) added to the agency's distress with new and troubling revelations about FDA's own scientific culture. UCS, an environmental group with about 100,000 members, asked the agency's staff scientists about scientific independence, professionalism, management, and outside interference at FDA. UCS sent surveys to almost 6,000 FDA scientists. Nearly 1,000 mostly senior staffers responded. Turn the page for the grim results...

• Three of every five respondents said they knew of cases in which political appointees from the Department of Health and Human Services or FDA "inappropriately injected themselves into FDA determinations or actions."

• Only 47 percent agreed with this statement: "FDA routinely provides complete and accurate information to the public."

• Four in five agreed that the "public would be better served if the independence and authority of FDA post-market safety systems were strengthened."

• The full results of the survey (available at www.ucsusa.org) are a bit more nuanced, but they still suggest that the agency is deeply divided and suffers from sagging morale.

• When asked how often FDA scientific documents and reports rely upon the best available science, just 77 percent said always or frequently. Only 73 percent gave similar answers when asked whether FDA determinations and actions are consistent with the scientific findings contained in FDA.

• Two thirds said they've never been asked, for non-scientific reasons, to inappropriately exclude or alter technical information. Another 18 percent say the question is not applicable.

• About half said they knew of at least some cases when commercial interests have "inappropriately induced or attempted to induce the reversal, withdrawal, or modification of FDA determinations or actions."

• Similarly, more than 60 percent of respondents said they did not know of cases in which "members of Congress have inappropriately injected themselves into FDA determinations or actions" or that the question was not applicable. It's a number that's difficult even to comprehend in a year when Plan B was seldom out of the news.

In addition, respondents were invited to provide their opinions in essay form. About half responded, many of them passionately. (For excerpts see.)

To find out more about the survey, Pharm Exec's associate editor, George Koroneos, recently spoke with Francesca Grifo, director of scientific integrity program at UCS. What follows is an edited transcript of the conversation.

Pharm Exec: Can you tell me a little bit about the history of your organization?

Grifo: We were founded by a group of MIT professors in the late 60s. They were concerned about nuclear security issues and wanted to make sure the science was really being taken into account. And that's pretty much what we do: Try to get the science into public debates.

The scientific integrity program was founded in response to a lot of the changes in the executive branch. Scientists across agencies and on advisory committees and in the community came to us. A group of 16 Nobel Laureates and National Academy members wrote a statement, which is on our Web site, objecting to the current manipulation of science. Out of that we began a campaign, and this year it was changed into a full-fledged program at UCS.

What was the catalyst for the US Food and Drug Administration Scientist Survey?

A number of scientists came to us about problems they were encountering at FDA, and we began to wonder if they were more pervasive than the anecdotal examples that we were getting. We have done surveys of other federal agencies. We did one of Fish and Wildlife Service and one of NOAA Fisheries. And we have others that will be coming out next year. We like them because they give us a snapshot of the agency.

The first step, which takes the longest, is combing through an agency's personnel records looking at job descriptions and people's educational background to see who are the scientists. That took a long time at FDA because there were 13,000 scientists to go through. And we came up with the 6,000—actually 5,918—that we mailed to.

We mailed across the country to the seven centers in the Office of the Commissioner because we felt like it was important to see how this looked across the country. The differences among the centers were not even statistically significant.

Of the scientists who responded, 62 percent were GS13s to 15s. That's the top of the General Service schedule. And another 34 percent were GS9s through 12s. So we really had high-level scientists.

Thirty-three percent had been at the FDA more than 15 years, 19 percent had been there six to 10 years, and another 14 percent had been there between 10 and 15 years. So three-quarters of the people we surveyed had been there more than six years.

People have been tempted to say, "Wow, these are just the angry or the malcontents." I think the best way to talk about that is to look at the essays. The information in them is the voices of scientists who are worried about safety and efficacy. It's not embittered people. It's people who are really committed to their jobs, committed to what they're doing at the FDA. In the course of the survey we had a lot of phone calls from scientists at the FDA because they were concerned and wanted to know if we were for real—who we were and was this for real or was it connected somehow to FDA leadership.

What FDA Insiders Say

They want to find out if their bosses were spying on them.

I think that was a real concern.

There is the other side, though, that thinks you might be more of a political group than a group of concerned scientists.

Well, we are a 501(c)(3) organization, and anybody who's familiar with the IRS code concerning that knows that we are severely limited in the amount of lobbying that we can do. By law, it's a very, very small percentage of our budget. I'm not going to say we don't lobby. Obviously we do take advantage of that small portion, but I think it's only two percent of our budget.

Let's discuss the survey a little more. Which questions do you feel are the most important?

Some things come out very loudly. One is that the scientists are worried about what they can and cannot say. That's incredibly important, and I think the numbers support their concerns. In one question, for example, more than a third of FDA's scientists disagreed or strongly disagreed with the statement that they were free to express within the agency concerns about public health without fear of retaliation.

The second theme I think has to do with where we need to go from here. For example, we have 792 scientists agreeing that the public would be better served if the independence and authority of postmarket product safety systems were strengthened.

At one point the survey combines two separate questions—one about separating the safety and efficacy functions at FDA, and the other about FDA strengthening its post-market product safety systems. Did you worry that this would be confusing?

When we created these questions, we worked very closely with a number of FDA scientists, former and current, and they were fine with that wording. They came up to us with that issue and said, you know, "This is a big concern." So that is where the wording came from. I don't think we loaded it in any particular way.

But it could be confusing.

It is. It's two themes. Obviously you get better information if you can separate these sorts of things, but we didn't have unlimited length in the questionnaire. In our minds the question was not just product safety but post-market product safety. That's what we were trying to get to.

The other thing to be clear on is that this does not come out in a vacuum. There's been a lot of hue and cry from a lot of sources, which had raised the issue of post-market product safety systems.

We were talking about what you feel were the most important questions.

Another is the question that asked whether the laws regulating FDA and FDA's structure needed to be changed. There, 63 percent agreed or strongly agreed. These scientists are feeling like there's a need for change.

The INTEGRITY of the scientific work produced by FDA could best be improved by...

The other very important questions I think have to really do with resources. This is not typically an issue for us at UCS, but we're hoping that other people will see this and realize that FDA currently does not have the resources it needs to really do its job. I mean, some of the essays say things like, "We just need a centrifuge." It feels like this agency has really been starved for money.

How do you look at numbers like these and determine what's appropriate and what's inappropriate? How do you determine what people really mean?

I'll just sidetrack for a minute to an analogy. Let's pretend that we had a university with 13,000 employees, which is approximately what we have at FDA. If 497 faculty members at that institution said the university was not moving in the right direction, there would be an enormous hue and cry. I think that's what we're trying to point out here—that the significant worker bees, if you will, are telling us they have concerns.

One question asks respondents whether they agree with the statement "I have been asked explicitly by FDA decision-makers to provide incomplete, inaccurate, or misleading information to the public-regulated industry, media, or elected senior government officials." Some people would say that FDA always provides incomplete information.

Well, there are several different ways of thinking about incompleteness. I don't think anybody would call results that were simply edited down incomplete. I don't think a reasonable person reading this would think, "Oh, we left out that paragraph about some minutiae of some particular drug and so therefore it's incomplete."

Should FDA reveal all its findings?

We feel that there is an enormous amount that is currently not being released that should be. What we find particularly worrisome right now is that the scientists don't feel like they can speak out when they have something to say that is in disagreement with approval. This gives them great pause. Several questions ask scientists whether they fear retaliation for positions they take. Those numbers should be zero.

If you look at academia or other models of scientific inquiry, disagreement is a normal part of the process and it needs to be encouraged, not discouraged. It doesn't mean that the scientist is going to get his way every single time. And I don't think that's what they expect either, but they do want to feel heard, and that's incredibly important to scientific discourse.

At what point do you draw the line between someone who is just complaining about the company and someone who's an actual whistle blower?

We have no evidence that the people in our survey are just complainers. In fact, the evidence that we have from the essays, from the caliber and the length of service, and the kinds of people that responded to this survey, all says to us these are serious scientists.

When you speak with these people on the phone, they're not grumping about their work place, they're not grumping about their bosses, those kinds of things. The first thing they say is, "I am so worried about the American people. I can't speak out within FDA because if I do, I'll have to leave, and if I leave, someone who doesn't understand the system as well as I do will come in and they won't be able to work these things through in the way that I am able to because of my experience and tenure here."

Some of these people wrote three and four pages of essays. If somebody was embittered, it would come out. And it's just not there.

People are clearly worried that scientists are being pressured to change or conceal results. Does the survey show that scientists share those fears?

Look at the question that asked them whether they agreed with the statement, "I respect the integrity and professionalism of FDA leadership," the questions about whether leaders and managers stand behind scientific staff who put forth scientifically defensible opinions that may be politically controversial. I think those tell us that FDA scientists are worried about big-picture issues and that they are concerned in particular about things that may be politically controversial or issues where there's commercial pressure.

How deeply does the survey go into that commercial pressure on scientists?

The thing we didn't have the chance to get into in depth but that's obviously a part of all of these conversations is the Prescription Drug User Fee Act (PDUFA), which comes up for reauthorization this fall. I hope the survey creates an opportunity for there to be vigorous debate about the impacts of those deadlines on the scientific work being done.

It may not be that every supervisor is worried about PDUFA deadlines and putting pressure on the scientists to make inappropriate decisions. It's rather that if that happens often enough, the perception is out there and gets a life of its own.

Many of the people who wrote essays said that, given the constraints of PDUFA, they found it hard to adequately pose questions and have the time for vigorous internal debate. They also said that because the people above them were being judged based on PDUFA productivity, they weren't creating the climate where those scientific debates could happen.

And those debates are important. You know, it just has to come out and they have to have the time to really spend looking at what industry is submitting.

When you look at the survey as a whole, what overriding concerns come through?

I think there are a couple of messages. One, I have big concerns about advisory committees and the way those are being run. That came out in the essays over and over again—the ideas of openness and conflict of interest and so on. We have big concerns about the integrity and professionalism of FDA leadership. We have big concerns about scientific candor. We know that Congress has a number of different pieces of legislation before it and we hope the voices of scientists can be a vital part of that debate. That's what's important to us.

What actions should FDA be taking here?

We don't do FDA. We do scientists. We don't want to prescribe the details of what FDA should do. Rather, we want to make certain that there's a process in which the scientific debate happens, the voices of the scientists are taken into account. That's what we think is the most critical aspect of this.

Roughly half of FDA's employees are scientists. And if you look at the agency's mission statement, it's very clear: protecting the public health, helping the public get accurate science-based information. It should be, in our opinion, very much a science-driven organization. Science is rarely the only thing taken into account when we create policy. We don't dispute that. What concerns us is when the science doesn't make it—free and unfettered—into a policy debate.

What has to happen to assure that scientists' voices are heard in policy debates?

Right now, as FDA transitions to new leadership, it's particularly important for that new leadership to come out and say, "We're not having this. We are, in fact, a science-based agency and we need to create some fairly significant structural changes to make sure that the voices of the scientists are heard."