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  5. Panel IV - Presentations by Consumer Groups, Prescription Drug User Fee Act Public Meeting November 14, 2005
  1. Prescription Drug User Fee Amendments

Panel IV - Presentations by Consumer Groups, Prescription Drug User Fee Act Public Meeting November 14, 2005

Panel III - Presentations by Patient Advocacy Groups 

MS. HENDERSON: Back on the record.

Okay, we'll ask our audience to come in and take their seats, and we will get started for the afternoon.

MS. HENDERSON: Our first panel for this afternoon will be a panel of presentations by consumer groups. And we are joined to today by William Vaughan, Alison Rein, Arthur Levin, and Diana Zuckerman. And we're going to start with Mr. Vaughan.

Bill Vaughan is currently senior policy analyst in the health sector for Consumer's Union, the nonprofit, independent publisher of Consumer Reports. Starting in 1965 he worked for various members of the House of Representatives' Ways and Means Committee, and he retired in 2001 as Health Subcommittee Staff Director for the minority.

Between 2003 and May 2005, he was Director of Government Relations for Families U.S.A., a national health advocacy organization.

Please join me in welcoming Mr. Vaughan.

MR. VAUGHAN: Thank you very much. And I'm here on behalf of Consumer's Union, publishers of Consumers Reports, which has about seven millionsubscribers. We're mostly known for evaluating toasters and flat screen TVs. And if you haven't done your holiday shopping, our new issue has some really great ideas.

[Laughter.]

But we also try to help consumers with the safest, most effective and most reasonably-priced prescription drugs. And we urge the FDA to use the opportunity of PDUFA extension to seek fundamenta legislative reforms in the Agency, to continue to bring increased emphasis to safety without slowing approvals, and help the American public understand what medical treatments are truly effective.

As part of this consumer panel, I find I agree with basically everything they're saying, so I won't repeat it all, but will stress a few items, in particular in support of Dr. Tilson, and CERTs, and the need for comparative effectiveness to help the American public what drugs really work and are effective.

And I'd also want to say that I agree with the pre-lunch patients panel. We are in this together. We basically all agree that the FDA needs more resources. We want an FDA that can walk and chew safe gum at the same time, if you will. Of course the FDA should approve quickly potentially life-saving medicines, at the same time it intensifies research on the long-range impact of those drugs. This should not be an either-or proposition. We're in this together.

I have a full written statement that I hope is before you all. And the FDA asked for an assessment of the overall performance of PDUFA to date. And while there are benefits resulting from the agency getting increased funds to speed review of new life-saving drugs, we believe the overall result of PDUFA has been to undercut the independence and objectivity of the agency.

By shifting resources to speeding drug approval, without a similar increase in drug safety, PDUFA has created a lopsided agenda that, in part, has resulted in the kinds of drug-safety tragedies we've seen in this last several years.

And on the question, "What should be retained or should be changed?" we believe that when PDUFA is extended, collected fees must be decoupled from specific pre- and post-performance goals that have been rushing the approval of unsafe drugs, and limiting follow-up safety efforts.

We believe a much larger level of income should be collected, since the amounts provided in PDUFA, coupled with impossibly tight Treasury appropriations, have been inadequate to fulfill the overall mission of FDA. And much of the increase should be used by the Agency to improve post-approval monitoring and safety, conduct prior review of marketing materials, and ensure that safety studies are completed to help consumers fully understand the comparative value of approved drugs.

Extending PDUFA is not our first choice for creating an agency that truly serves the public. We believe the Federal agencies that carry out the public's business should be funded by the general treasury to avoid conflicts of interest. As such, we support legislation by Representatives Hinchey, DeLauro and Stupak that would designate that PDUFA fees be deposited into the General Treasury, and that an equal amount transferred to the FDA as mandatory spending, with no strings attached.

The Bill also includes sections very similar to S. 930 by Senators Grassley and Dodd, that we've endorsed, creating a separate Office of Drug Safety that is appropriately funded, with clearer authority, including civil monetary penalties, to require post-approval safety studies that actually get completed; prior review of DTC adds; immediate adjustment of warning labels; and risk-management programs.

We believe that these types of safety authorities, along with the reforms contained in S. 470 by Senators Dodd and Grassley, that ensure a publicly accessible clinical trial data base would result in a much safer world of prescription drugs, without slowing approval. These measures will take additional resources, but they will fulfill the Agency's mission by ensuring that safety and research have an equal place at the drug approval table.

There's an ancient folk wisdom that he who pays the piper calls the tune. PDUFA fosters a public notion that FDA is too friendly with the very industry it is supposed to regulate. As has been reported, some in the FDA have referred to the drug industry as "clients." As the September 2002 GAO report on the effect of user fees noted, "The process may have created problems with employee retention and morale."

There is, indeed, a need for more resources, yet there are realistic projections that the Federal debt--Federal debt--will rise $4.6 trillion over the next decade, and that by 2015, our annual deficits will still be running in the $400 to $600 billion a year range before the full impact of the retirement of the baby boomers.

In short, the Federal budget is a disaster, and it's completely unrealistic to expect that if PDUFA expires the Congress will make up the difference out of general revenues. Without PDUFA's resources, it is hard--very hard--to imagine how the FDA would function. Therefore, PDUFA extension is key, but hopefully without industry-entangling strings.

And industry is best served by the drug-approval and monitoring system that the public trusts. By helping to adequately fund the FDA, industry will be able to begin recovering that vital trust.

As I said, we need the money for post-market safety studies, for aggressive use of new data bases, such as the Medicare drug data base that's coming available, to detect long-term safety problems. Given the long history of marketing violations, the FDA needs the resources to review all marketing materials before they are distributed to providers and the public.

The FDA needs more resources to help bring lower cost safe drugs and devices to market. And we're talking the backlog in generics; the need to find biologic generics that are safe; and then also doing sure safety in the institutional review board Phase I trial process. Bloomberg news reports in the last two weeks, if they're half correct, if they're half accurate, describe a scandal and a tragedy that threaten individual lives and the very quality of the drug-testing process. And the FDA needs to get on top of what's happening at the IRBs.

We believe that the government should require more scientific, evidence-based studies to help the public understand which drugs are truly effective and safe, and how drugs compare in effectiveness. To slow the unsustainable growth in health costs, we need a comprehensive understanding of what the best course of treatment is, across the variety of treatment options: surgery, medicine, radiation, you name it.

The Medicare Modernization Act provided the beginning of comprehensive comparative effectiveness studies in Section 1013. If this section were adequately funded to undertake a wide array of high-quality trials, the nation could save billions, we think--billions of dollars--in the future by eliminating ineffective medical treatments and medicines.

Unfortunately, the battle in Congress this year--and it's been a tough one--is whether the amount appropriated would be $15 million or $20 million. Big deal. That's a tiny drop in the bucket, compared to what we need.

And given the long-term Federal fiscal situation discussed earlier, Section 1013's potential will be hard to realize. Therefore, we hope that PDUFA reauthorization will be accompanied by provisions for many, many more Phase IV trials that require new drugs be compared for effectiveness against other drugs. PDUFA resources should be available to help FDA staff ensure that these studies are high quality and completed on time, perhaps in supportive CERTs. These studies, combined with the kind of data that should be available from the Medicare payment data base will finally begin to give us hard information on what works best in the world of health.

One last thing--the gentleman from the Parkinson's group kind of talked about this--is that consumers are involved in the consultation process on PDUFA extension, but only the industry is involved in the negotiation process, according to that law. And yet in reading the law, there is nothing that would keep the FDA from inviting consumers and patients into that negotiation. And I hope, for the sake of building trust, that the process does become more open.

Thank you very much for your consideration of these recommendations.

MS. HENDERSON: Thank you very much, Mr. Vaughan.

Our next speaker is Alison Rein. Alison Rein is the assistant director of Food and Health Policy at the National Consumers League. Founded in 1899 to bring consumer power to bear on marketplace and workplace issues, NCL is the nation's oldest consumer organization.

Ms. rein designs and coordinates campaigns and other activities around NCL's priority issues, including food safety and nutrition, medication safety, and health care quality. In the last year she has expanded NCL's involvement as a consumer stakeholder in the national discussion about emerging health technologies.

Ms. Rein?

MS. REIN: Thank you and good afternoon.

On behalf of National Consumers League I'd like to thank you for the invitation to share a consumer-oriented perspective of the Prescription Drug User Fee Act. And I'll skip over a couple sentences that I had inserted about NCL, since they were already stated. But I will add that from the first Pure Food and Drug Law passed in 1906, to the more recent FDA Modernization Act, NCL's been working--often alongside the Agency--to ensure that the public's well being is adequately represented and protected.

And so it's in this context that NCL calls on the FDA to seize the upcoming PDUFA reauthorization process as an opportunity to critically examine the impact of the program to date and consider opportunities for enhancement moving forward.

Before going any further, however, I'd like to pause and echo one of the points that was raised by Bill previously, and that is an observation about the process of comment. There's a growing perception that the FDA has become too intimate with the companies over which it has regulatory authority. And this is view is only exacerbated by the fact that the public has relatively little opportunity for input into the rules governing product review and oversight.

PDUFA provides a clear example of this. When PDUFA was first created, the FDA consulted with Congress and the life sciences industry, leaving health care consumers--arguably the Agency's real customers--out of the loop. The process was made slightly better in the PDUFA III process, as the FDA was charged to also consult with academics and consumers. While a welcome change, consumers are still conspicuously absent from the actual negotiation process. And until consumer interests are directly represented in the final negotiations process, the FDA will not truly serve its real customers.

So, all of that said, I would now like to turn to the specific question posed for this public meeting. To the first--"What is your assessment of the overall performance of the PDUFA program thus far?--NCL has a somewhat mixed response. In the interest of time I'll just make two quick points to address this question.

First, NCL fully supports the ideal that enhanced drug approval processes benefit everyone. However faster approval does not always mean better. Unfortunately, review time is currently the only performance goal used by the agency to determine success. Throughput, in and of itself, is not a sufficient measure.

Until there is a shift away from the current paradigm of getting drugs to market as quickly as possible, while giving little consideration to product safety in the applied or real-life setting, Americans will continue to be exposed to unnecessary, and often deadly, risks.

I find it a little disturbing: some of the research presented this morning may be taken as proof-positive that PDUFA has had no negative impact on patient safety. Analysis of the very small sample of actual product withdrawals as the primary endpoint does the issue a tremendous disservice.

Instead of the overly simplistic metric of "product withdrawals," researchers should consider broader measures of patient safety, especially given that, many would argue, that there are many dangerous drugs still on the market, and many patients who have suffered as a consequence.

As a further challenge to this notion, I would simply pose a question: Since when have we been satisfied with the status quo? Should we not be striving to reduce, and not simply just maintain, threats to patient safety?

Second point: NCL believes that the current structure of FDA funding, insufficient in total and with an ever-increasing percentage coming from user fees, forces the Agency into a position of robbing badly needed resources from other important program areas that are vital to preserving and protecting the public's health. Evidence of this disturbing trend can be seen in chronic staffing deficiencies almost throughout the Agency; persistent inattention to existing programs such as MedWatch; lack of capacity to initiate much needed adverse event monitoring and reporting systems; and reduced food safety inspections--to name just a few.

AS a result, the Agency is in jeopardy of losing the support and confidence of the American people, something it cannot afford to do at this time.

While these are very real and serious issues, revealing some very real problems with the current system, reverting back to Agency funding without PDUFA does not appear to be a viable option. Given the shape of the Federal budget, and our society's increasing reliance on FDA-regulated products, and the need for expanded FDA activity in the area of product safety, it would seem reasonable to actually increase the level of user fees. This would only be acceptable, however, under the conditions that: a) the increase in user fees does not translate into a diminished total budget allocation from Congress; and b) the user fee funds be applied to the general FDA budget, with no conditions for its use.

While Congress has to date allowed the regulated industries to dictate to FDA how FDA allocates its resources, there is too much at stake to allow this pattern to persist. One potential remedy might involve introduction of a sliding user fee schedule that actually incents drug development in clinical areas identified by the Agency and relevant stakeholders. This type of progressive fee system might do more to more to stimulate innovation in clinical areas of intense need.

So I've already begun to answer part of the second question posed for this public meeting, which is: What aspects of PDUFA should be retained, or what should be changed to further strengthen and improve the program?

NCL could suggest many further modifications to the current PDUFA structure, but I will focus the rest of my comments on one in particular: the introduction of a new fee for DTCA review.

NCL has long been interested in ensuring that consumers received accurate and useful information about their health care, including information about the safe and effective use of prescription drugs. If DCTA is to remain an integral part of this communications process, then we would propose that product sponsors be assessed a fee as part of their submission of any DTC add, regardless of medium, to the agency.

The revenue derived from the new fee could be used to support a number of currently under-funded agency activities, including, but not limited to: funding of post-market safety studies, as deemed necessary, on a case-by-case basis; expanded use of large data bases to detect safety issues not identified not in the pre-market clinical trial setting; expanded use of secondary data to conduct relative safety and effectiveness analyses; increased expenditure on public information sharing about emerging safety issues, as well as disease awareness; and hiring of additional staff to review and respond to industry feedback in a timely fashion on all DTC adds pre-deployment.

In addition, FDA should be granted the authority to place a moratorium on all DTC advertising for new drugs deemed by the agency to have inadequate safety information. Based on available safety data, the Agency could be given latitude in determining the appropriate length of the moratorium on a product-by-product basis.

NCL also would support added a third "provisional" status for some new drugs. Such a status would allow for limited exposure of the product to appropriate patients, thereby mitigating the likelihood of inappropriate use and overexposure while additional post-approval safety data collection is ongoing.

In closing I would like to reiterate the point that if FDA budgets continue to shrink at the expense of PDUFA-related programs and review goals, the Agency's ability to satisfy its mission of protecting the public health will diminish--and with it, the public's remaining trust.

Thank you for your consideration of these comments and recommendation.

MS. HENDERSON: Thank you very much, Ms. rein.

Our next speaker is Art Levin. Mr. Levin is director of the Center for Medical Consumers, a New York City-based nonprofit organization committed to informed consumer and patient health care decision-making, patient safety, evidence-based high-quality medicine, and health care system transparency.

He was recently appointed to the IOM's board on health care services, which has been responsible for overseeing their decade-long effort to improve the quality and safety of America's health care system. No stranger to FDA, Mr. Levin has been a longtime member of our consumer nominating workgroup that recommends consumer representatives for FDA advisory committees; and himself is the consumer member on the Drug Safety and Risk Management Advisory Committee.

Please join me in welcoming Arthur Levin.

MR. LEVIN: Thank you. A lot of what I'm going to say is going to sound repetitive, but I think it says to all of you that consumer organizations are really on the same page for the most part when it comes to what we think about PDUFA in the past, and what we hope for it in the future.

Like Bill, I'd like to just sort of make a statement of principle that some of us continue to be troubled by this shift that PDUFA represents, from the historic way that the nation's public health activities were funded prior to 1992. Until that time, the FDA's essential public protection programs were funded out of general revenues through the Congressional budget appropriations process. And we think that should be the rule, although we recognize it is not.

That said, there's little doubt in my mind that PDUFA, through its three iterations has substantially achieved what it set out to do: it's provided the Agency with adequate resources to meet very specific, relatively short review time frames more that 90 percent of the time. Now, we've heard that 50 percent of FDA's resources to do this come form industry. And it's this richness of resources that enables FDA to complete reviews within the specified timeframes, and provide on-demand consultation to the sponsors, aimed at improving the quality of NDAs--a laudable goal and, we've heard today, perhaps a loss-leader for FDA.

Under the law, FDA performance is evaluated on what percent of its application reviews are completed within the prescribed timeframes for priority and standard review. But these are pure management goals, negotiated by industry with FDA, and may have nothing at all to do with a positive effect on the public's health.

We have also not formally determined if the skewing of CDER's resources towards the drug approval process has had unintended consequences on their ability to meet other responsibilities or, indeed, the effect on other centers within the Agency to meet their responsibilities.

Now, many of us believe that such skewing of resources is at least in part responsible for drug safety surveillance, especially post-market, being a stepchild of CDER. And I know that Steve Galson says that more than 50 percent of the resources within CDER are spent on safety, but I suspect that's taking everything into consideration: pre-, peri- and post-market.

Public and political clamor tends to focus on access to new drugs rather than such mundane public health matters as assuring the safety of radiation-emitting medical technology for canned tuna. Previous FDA briefings have revealed other centers' programs may be sufficiently underfunded and understaffed so as to jeopardize public safety.

Now, over the years advocates have been concerned that a speeded-up review process might present risk rather than benefit to the public. And some FDA review staffers have given credence to this concern in interviews. But there's been a paucity of studies to confirm, deny or appraise the degree of such risk. One study conducted by FDA staff some years ago argued that PDUFA's speed-up of review times was not a cause for concern. That investigation was prompted by the withdrawal of five drugs in a 12-month period. The researchers concluded that reduced review times under PDUFA were not the cause of this troubling spike in withdrawals.

Yet perhaps the most interesting table in that article, published in JAMA, May 12, 1999, showed that almost 18 million Americans had been exposed to risk from the five drugs prior to their withdrawal. And I guess I would ask: is that level of exposure acceptable?

And as Alison pointed our, the studies we've heard from today also use the metric of withdrawal rates, rather than looking at the population exposure issue.

In this era of experience-based medicine, it seems strange that we've yet to do the study that would tell us whether PDUFA has or has not made an important difference in the lives and well-being of sick Americans. After all, it's not the numbers of drugs that come to market, it's their quality and their effectiveness and their safety that count.

So, as we continue to discuss reauthorization of PDUFA without the science to support either its continuation or the exact form its continuation should take, I think w need to pause and reflect on the paucity of scientific evidence to determine what the right road to take is.

And another issue, it seems to me that we seem to skirt around is that we're stuck with anecdote and belief that a faster process of review prior to approval is good for the public health. There is simply a lack of evidence that FDA's admittedly pre-PDUFA slow rate of review really caused any excess morbidity and mortality in the United States, when compared with other countries. In fact, although most new drugs are first approved in the U.S.--a turnabout from the pre-PDUFA years--the health status of the populations of member nations in the now new drug-deprived European Union continues to outrank the U.S.

The notion of U.S. drug lag, borne our of displeasure in certain quarters with the KHA amendments of '62 may be mythical. A study published in 1996 looked at 35 drugs marketed in G-7 countries and Switzerland between 1970 and 1988. And all of these drugs were assessed as having therapeutic significance by experts in this country and in those other countries. The pre-PDUFA, pokey-review FDA approved most of these drugs before they were approved in the U.K. And the U.S. ranked third overall in getting those 35 drugs to market.

Given the political reality of America's national finances, the continued infatuation with collegial, rather than regulatory, relationships between the public and private sectors, and the phoenix-like quality of the drug-lag myth, I, like other speakers here today, assume that PDUFA, warts and all, is likely to be with us for some time to come. And if that's the case, there are critical concerns I would like to see PDUFA IV address: primarily to strengthen the Agency's ability to protect the public health.

There can be little doubt that concerns about the ability of FDA to conduct safety surveillance once drugs are marketed have grown exponentially over the last two years. Besides obvious deficiencies in surveillance, the Agency also appears to lack necessary authority to take decisive remedial action when the public health is threatened. Such lack of authority relegates the FDA to a negotiating role in regard to risk-management interventions to reduce harm of marketed drugs with demonstrated safety problems, or those sending strong signals of such problems.

I would suggest that if PDUFA IV does nothing else, it must provide sufficient resources to move the Agency's capacity to assure the safety of marketed products from the 20th to the 21st century.

Now, most experts appear to agree that the Agency's current reliance on a passive, retrospective reporting system dooms it to often fail in spotting serious adverse events associated with drug. MedWatch, the Agency's voluntary reporting system for adverse occurrences related to a drug appears quite capable of unearthing rare and serious events. But because the events are rare, the potential harm to a population of users is relatively small--even though some individuals may suffer a serious or fatal injury.

The passive collecting of voluntarily submitted reports, and the reactive surveillance that follows from such reports is a far from sufficient safety assurance approach. We need to carefully think about how to streamline MedWatch so as to optimize its limited potential, rather an rushing to pour in more resources which will not buy us much in terms of improved safety. An optimized MedWatch, for example, would likely still have lacked the capacity to have picked up the signals of drug-caused increases in risk of heart attach and stroke experienced post-market by users of Vioxx, Bextra and Celebrex.

The supposed second line of defense after the approval and review process, post-market clinical trials, or Phase IV, is unfortunately the Agency's Maginot line. Consider these numbers published in the February 18, 2005, Federal Register. There were 1,191 open commitments of post-market clinical trials. Of these, 812--68 percent--had not even been initiated; 219, or 18 percent, were ongoing; and only 143, or 12 percent, had been completed with a final report submitted.

But FDA would have to be granted substantial new authority to force sponsor compliance with study commitments, something Congress may not be willing to do. Without such a grant of additional authority, post-marketing studies may never become a reliable mechanism for surveillance of drug safety post-market. And it's important to acknowledge that clinical studies are complex and costly, and that may limit their utility, as well.

What is most needed is a shift from reliance on a passive, reactive system, to one which is active and proactive. And this would involve using large administrative data bases, where drug use and clinical history of individual patients can be easily linked, and real-time monitoring for safety signals is a possibility.

In the public sector these data bases would include the VA and DoD's active-duty and Tri-Care populations. And I'd like to just comment that, despite efforts in 2000 by then Secretary Tommy Thompson to have the FDA, CDC, AHRQ and these other Federal programs share safety data and other data, that still, to my knowledge, is not a fact.

In a few years Medicare Part D will hopefully provide an important data base linking drug use and patient clinical records to be able to mine safety problems, but the program appears headed for a troubled takeoff over enrollment and cost, and may not provide reliable data for safety monitoring for some time.

Large electronic data bases exist in the private sector. For example, Kaiser Permanente has literally spend billions converting six to eight million subscribers to an ambulatory EMR system that allows a linkage of drug use to clinical histories. While the FDA has recently stuck a toe in these private-sector data base waters, it really requires more of a complete baptismal approach.

The ability to use proactive real-time surveillance systems may also suggest that we need to think about an addition to the current all-or-nothing approval process. Some sort of conditional approval of drugs where there's a reasonable suspicion of safety problems, or a reasonable hypothesis suggestive of safety problems is likely needed. After all, we agree that many safety problems cannot be uncovered in pre-approval trials because of small sample sizes, short treatment durations, and the exclusion of so-called high risk patients. This would move risk management to a strategy that is not retrospective, but one that is prospective, and I think I would call a "limited marketing" approach.

The cost of establishing linkages with large public and private data bases will not be insignificant, nor will the cost of getting Federal agency data bases to talk to one another. And simply collecting a lot of data is not enough; in fact, it could overwhelm the FDA altogether.

The FDA must be given the resources necessary to update its computers, and the human capacity for real-time trolling of large data bases for safety signals, and have the skilled staff available to drill-down on those signals, where appropriate. This will require significant start-up costs, new hires, and continued training and operational support.

So, my conclusion: if we're going to have a PDUFA IV, it must include sufficient new resources to enable FDA to do meaningful drug safety surveillance using 21st century technology. Now, that said, I recognize the potential for apparent or real conflict of interest between industry and the Agency, when industry money is supporting safety oversight may even be greater and of more concern than when it supports pre-market approval reviews.

I would therefore suggest that we must be careful to design any supplemental user fee program to allocate more money to drug safety so that the revenue derived is detached from the specific sponsor source. And we've already heard Bill refer to Congressman Hinchey's proposal to do just that.

We need to hear other proposals that would meet the challenge of avoiding potential conflict of interest head on, while providing the resources critical to support a 21st century safety surveillance system. As important as improving FDA's capacity for drug safety surveillance may be, any proposal that does not recognize the potential conflict of interest and attempt to deal with it up front in the public interest is, in my mind, not supportable.

MS. HENDERSON: Thank you very much, Mr. Levin.

Finally, for this consumer advocacy panel is Dr. Diana Zuckerman, the president of the National Research Center for Women and Families, a nonpartisan, nonprofit research and education organization that works to improve policies and programs that affect the health and safety of women, children and families.

From 1983 to 1995, Dr. Zuckerman worked as a staffer in both the House and the U.S. Senate, working for the House subcommittee that has oversight jurisdiction over the Food and Drug Administration. In 1995, Dr. Zuckerman served as a senior policy advisor in the White House, working for the First Lady and the Office of Science and Technology Policy.

Since 1996, she has served in leadership positions at nonprofit organizations, and has been president of the National Research Center for Women and Families since 1999.

Please join me in welcoming Dr. Zuckerman.

DR. ZUCKERMAN: Thanks very much.

I'm delighted to be here, and to be with my distinguished colleagues. And let me just say that it doesn't always happen that different consumer groups with different perspectives are in so much agreement, but in this case we are.

I'm going to go in a slightly different direction, however, in my presentation just to talk about the reality of who are using the drugs that are being approved, and why it's so crucial that PDUFA really focus on safety issues prior to approval as well as post-market; and how important it is that, at the same time, standards are being maintained and criteria are being met for approval deadlines, that the safeguards that are so essential to FDA's appropriate functioning and mandate also be kept.

[Slide.]

These are the healthy people that are in clinical trials. And, you know, there's a range; there's men, and there's women, and there's some range in age. But basically we're talking about studies that are generally done, clinical trials that are generally focused, on health, well-functioning men and women. And not too many of them either; relatively small numbers. But remember that that is going to translate to a huge number of people taking the drugs that are approved.

From 1993 to 2003, the number of prescriptions that were purchased increased 70 percent, from 2 billion to 3.4 billion. And at the same time, the U.S. population growth was only 13 percent. So there was a 70 percent increase in drugs, 13 percent increase in population. And when you look at a list of the top 300 prescribed drugs in the United States last year--and I'm talking about prescriptions that were actually dispensed--the top 300 range in numbers from a little over 2 million to over 92 million for the year. So you're talking about huge numbers of people, and a very diverse population that don't look exactly like this.

[Slide.]

African Americans, obviously, are using a lot of medications, and yet they are not necessarily included in the clinical trials. Just this past September the FDA came out with a guidance for industry on the collection of race and ethnicity data in clinical trials. But much to our disappointment, that guidance only talks about the categories of race and ethnicity, and to make sure that they're consistent with other categories used throughout HHS. It doesn't actually require the companies to include any African-Americans or any Asians or any Hispanics.

And so you have a situation where clinical trials are taking place that do not have to include some of the major ethnic groups in the country. And the populations in these clinical trials do not reflect the diversity of our country. And that's important, because although we know, as educated people, that race is a construct that is not necessarily very genetic or biological, we also know that different ethnic and racial groups, as categorized in this country, do tend to respond differently to some medications. And of course you know that, because FDA has responded that by approving a drug specifically for African-Americans. And just this past weekend the New York Times, I think it was, did an article talking, again, about racial differences for African-Americans in heart disease.

So we know that it's very important that drugs be tested, but there's no requirement that companies do so. And we don't know how often they do so. And when PhRMA puts their statistics out on who's using what drugs, they also don't talk about the racial and ethnic groups that are using them. So there's a lot of unknowns.

But what we do know is that from now on, supposedly, the categories will be appropriate; at least consistent with other HHS agencies. But that doesn't mean that there will be a single African-American, a single Hispanic, a single Asian-American or any other particular group in any of those studies.

[Slide.]

And then there's age. These are, I would call, the "young old" in this photograph. It doesn't really capture the fact that there are millions of Americans that are a lot older than this, that are taking a lot of medications. And they're taking a lot of them all at once.

My 88-year-old dad is taking about 10 different medications in the morning, and eight different ones at night. What kind of data are there that will say to anybody prescribing these medications what's safe for him? And there are a lot of Americans in the same position that he's in: in their 70s, in their 80s, taking medications that they may be metabolizing differently, and medications that were not really testing on people that old, and certainly not on people who are taking many different medications at once.

[Slide.]

And then there's women. Now, I think the FDA has done a better job in making sure that women are included in clinical trials. But a GAO report that came out in 2001 specified that we don't really actually know that much about how many women are in how many of these clinical trials that are being used.

And these are all the kinds of standards that should be part of PDUFA to make sure that drugs are being tested on the people who will take them, and to make sure that they're safe and effective for the people who will take them.

[Slide.]

And then there's age. There are young women, there are kids. There are more kids. There are our kids.

And we know that kids are taking a lot of medications. There was an article just recently about how many kids are now taking sleeping pills; Ambien being one of them. Ambien's also an extremely popular drug taken by people over the age of 50. I prefer not to think of those as "old" people, since I myself am over 50. But, let's face it: people over 50 might react differently; certainly people over 60 might react differently to a drug. Kids under 18 might react differently to a drug. They are taking these drugs. And we actually know relatively little about what's going to happen to them.

[Slide.]

So, when you think about the diversity of the people taking drugs who are or are not necessarily in the clinical trials that the drugs are studied on, I think it's really important that we just use this as one specific example of how we need to make sure that the standards being held to are not just the speed with which a drug is approved, but the safeguards to make sure that it's tested for safety and efficacy, not just on these people, but all the people who are going to take them.

Thank you.

MS. HENDERSON: Thank you very much, Dr. Zuckerman.

And thank you to this panel.

Panel V - Presentations by Industry Groups

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