Speeches & Testimony

Evaluating the Effectiveness of the Food and Drug Administration Modernization Act
May 3, 2001

Mr. Chairman and members of the Committee, thank you for this opportunity to speak with you today about the reauthorization of the FDA Modernization Act (FDAMA). I am Abbey Meyers, President of the National Organization for Rare Disorders (NORD). NORD is a non-profit voluntary health agency dedicated to the identification, treatment and cure of rare "orphan diseases." NORD is the primary patient organization that advocated for the Orphan Drug Act of 1983, which is one of the most successful and important health statutes that Congress ever passed.

One of NORD's primary goals is to promote the development of new treatments and cures for rare diseases and to make these therapies accessible to patients. Under the Orphan Drug Act, a rare disease is defined as a health condition that affects fewer than 200,000 Americans. Keep in mind that there are more than 6,000 of these disorders, cumulatively affecting an estimated 25 million Americans. NORD's mission, therefore, is enormous and very much reliant on the successes achieved by academic scientists, pharmaceutical and biotechnology companies, medical device manufacturers, and most of all, the Food & Drug Administration (FDA), which regulates these entities.

The FDA's mission is to "protect the public health by ensuring that human drugs are safe and effective. But since 1992, when "user fees" were first implemented, the public's trust in the agency has eroded. FDAMA reauthorized user fees and authorized "pediatric exclusivity," but its primary purpose was to speed the approval of more new drugs and devices, even if those drugs and devices were relatively unimportant to the public health. Just look at the seven drugs that were approved after 1993 and then removed from the market due to severe adverse reactions and deaths. Not one of these pharmaceuticals was a life-saving drug. They were drugs for heartburn, diabetes, and irritable bowel syndrome (chronic diarrhea), a painkiller, a blood pressure medicine, an antibiotic, and a diet pill. There was absolutely no reason to rush them to market. Given enough time to study the data, the FDA might have more adequately identified their risks and kept them off the market.

Consumers nationwide have begun to question FDA's true mission. Is the FDA a government agency established to protect the American public, or is it merely an extension of the pharmaceutical industry? Can we, as "stakeholders," trust the scientific judgment of the regulators when the FDA refers to the pharmaceutical industry as the agency's "customers"? I would also remind the Committee that the public is not merely a "stakeholder." We are the ones who may live or die based on the FDA's decisions.

The Prescription Drug User Fee Act, or PDUFA, was enacted to provide sufficient funding for the agency to hire the additional staff needed to review new drug applications at a quicker pace. In exchange for user fees, the FDA was given the responsibility of meeting very specific "performance goals." These performance goals, often referred to as "deadlines," have resulted in what some FDA officials refer to as a "sweat shop atmosphere." For example, for each new drug application submitted to the FDA, reviewers must master volumes of data in less than six months or a year, while juggling many other tasks. They quickly burn out from the intense pressure to perform, and often leave the agency in less than two years and go to industry to earn higher salaries. Performance goals create another unintended consequence -- companies have an incentive to delay submission of voluminous data, putting the agency under tremendous pressure to meet user fee deadlines without adequately analyzing the data. It appears the industry has the best of both worlds - they get their quick approvals AND they hire the scientists trained by the FDA.

Given the fact that pharmaceutical firms considers PDUFA "their" program (and I quote, "The time to approval in the review process has been coming down markedly since WE instituted the program in 1992"), it is probably a political reality that PDUFA will, in fact, be reauthorized because it is seen as a way to get products to market quicker with minimal erosion of patents.

But before PDUFA is reauthorized, we feel that consumers and patients must have assurances that the primary mission of the FDA is to protect and serve the American public - not to improve the financial picture of the pharmaceutical industry. As you consider reauthorization of FDAMA, therefore, we ask that you consider the following suggestions:

The politics of FDAMA

FDAMA was enacted during the Clinton administration, and some suspect it fell victim to the "reinventing government" initiative. Congress wanted to cut back federal spending, so "user fees" were implemented under PDUFA in 1993. FDAMA incorporated and reauthorized user fees in 1997 and, at the same time, was supposed to make the FDA more "user friendly" to the drug and device industries. Government regulatory agencies were told to be more cooperative with the industries that they regulate, and President Clinton specifically asked FDA administrators to trust industry as "partners, not adversaries."

Many consumer groups opposed FDAMA because they felt it would lower the safety and efficacy standards for new drugs, inflate FDA's resources for new drug reviews, and in turn deflate resources in other areas of the agency that are critical to the public's health. FDA would no longer be the "gold standard" for the world's health authorities, and nothing in FDAMA indicated that American consumers would be the agency's real "customers." Thus, the agency would not become more "user friendly" to the public. In fact, Congress, FDA and the regulated industries negotiated the law, and consumers were specifically omitted from the debate.

The changes that FDAMA brought about were NOT intended to enhance or protect the public's health. In fact, the agency had implemented critically important rules in the 1980s under Commissioner Frank Young during the Reagan administration for giving "priority reviews" to breakthrough drugs for serious and life-threatening diseases. But the pharmaceutical industry lobbied Congress for FDAMA on the basis that the FDA was taking too long to get "life-saving" medicines to the public. The truth was that life-saving medicines were already being speeded through the process, but the standard "me-too" drugs were taking more time than the industry wanted. Undoubtedly, FDAMA would not have been enacted if the arguments had been framed in terms of "speeding new diet pills to the market."

In 1988, only four percent of new drugs were approved first in the United States. By 1998, 66 percent of all new drugs were approved first in the USA. But, being first out of the gate does not necessarily mean you will win the race. When faulty drugs are rushed to approval, the "prize" for being first may be unnecessary exposure to negative side effects or death.

Review Time vs. Safety

The approval time for New Drug Applications (NDA) has decreased dramatically since PDUFA was first enacted. Back in 1993, the medial approval time was 24.1 months. In 2000, that figure plummeted to 11.2 months, or about 54 percent. If you look just at those statistics, I suppose you could say that PDUFA has been a resounding success.

However, there have been far too many withdrawals of marketed drugs after they have killed and disabled people, casting a serious shadow over the agency's credibility and competency. The publicity fueled by these withdrawals has further cast doubt on whether the user fee program is in the public's best interest. Based on those withdrawals, it is quite apparent to many that the FDA should not be subjected to the pressure cooker atmosphere created by PDUFA. Products are being rushed through the review process and, as a result, consumers are being exposed unnecessarily to sometimes dangerous and life-threatening drugs. Human beings are not guinea pigs, gentlemen. When FDA determines that a drug is both safe and effective, we take them at their word.

NORD believes the agency's success must NOT be measured by the speed of its work, but rather the completeness and scientific soundness of its work. In fact, some of the drugs that have been removed from the market in recent years might have been approved with more adequate labeling if FDA had enough time initially to recognize adverse effects, and to require appropriate labeling when the drugs were first approved. FDA reviewers must be given the latitude to review new drug applications at a decelerated rate if it is deemed scientifically and/or ethically necessary, especially when a drug is not a life-saving therapy. Let the reviewers do what they have trained years to do. Of course, everyone wants to see life-saving drugs come to market quickly, but only if they have been determined to be safe and effective. Remember the first law of medicine - First do no harm.

The agency should not be forced to take a "one size fits all" approach to drug approval; it is wrong to require FDA to spend the same amount of time to review all standard or priority drugs and biologics. Some will need more time. Some will need less. Safety and efficacy should be the only true measure of whether a drug is approved or not.

It is my understanding that eleven or more drugs have been removed from the market since 1993, but seven of them were first approved for marketing after 1993. In many of these cases, FDA "negotiated" labeling changes with the manufacturer, and left the drug on the market, hoping that doctors would notice the new warnings and prescribe the drug properly. Of course, health care providers usually don't reread labeling once a drug has been on the market, so after more deaths and serious adverse events, the FDA finally banned the drugs. The fact is the FDA seldom orders a company to change its label. Rather, they "negotiate" with companies over wording, and these negotiations can last for many months while manufacturers try to get wording that will have the most positive spin to enhance their marketing plan. We believe that FDA should be given the authority to order immediate labeling changes without negotiations. FDA's role is to protect the public's health. Manufacturers should not be telling the regulators how to regulate the regulators! Adverse Event Reporting

The United States has a voluntary system of adverse event reporting (AER). It relies on doctors, hospitals, consumers and manufacturers to report adverse events, but the FDA doesn't have sufficient resources to analyze the data and try to identify red flags that may point to public health disasters (e.g., heart problems caused by diet pills). Even with the incompetencies of the  

current AER system, voluntary reports of adverse events from pharmaceuticals rose 89 percent between 1993 and 2000. This alone should signal that too many new drugs are reaching the market before they are adequately studied. The rush to market is NOT for the sake of the public; it is solely for the sake of the industry.

Reauthorization of PDUFA must change this mindset and focus the law on public health protection and enhancement, including stronger FDA authority to analyze adverse events and to protect human subjects in research. To date, the FDA has no bioethicists on staff, no authority to stop a clinical trial if an informed consent document is inaccurate or misleading, or even if the study is unethical. Most clinical research today is funded by the industry, not by the government, and privately funded research does not have to obey the Common Rule. FDA should have the authority to enforce patient protections for privately funded research, and it must be given the funds to do this. Moreover, Congress should mandate adverse event reporting so that severe reactions to drugs can be tracked. Post-Marketing Surveillance Under FDAMA the FDA can ask manufacturers to perform post-marketing studies, but such studies are not mandatory. Even if the manufacturer agrees to such studies, the FDA does not have the authority to penalize the company if the studies are not conducted, and the FDA is the first to admit they don't even know if companies are doing them. FDA usually asks for post-marketing studies when they have rushed a priority drug through the approval process, but there are still unanswered questions. Often, once these drugs are used in the real world where people take other medicines, or have other illnesses, adverse events will occur.

At a recent Food and Drug Law Institute educational conference, industry argued that the FDA "has no jurisdiction in the area of risk management". We happen to agree with the FDA that the industry's position is "disingenuous." At the same conference, Jane Axelrad, Associate Policy Director for the FDA, said, "Drug companies have task forces out there bombarding doctors with details about drugs and this - along with direct-to-consumer advertising - is clearly influencing prescriber practice.

We ask that you make these post-marketing studies mandatory, and give the FDA the authority to assess penalties when companies do not do what they have promised to do. Post-marketing surveillance does not "step on the toes of the practice of medicine." Rather, it goes to the very heart of the mission of the FDA - to protect American consumers.

As prescribed by law, user fees can be employed for very specific purposes ONLY. They cannot be used for critically important public health functions such as adverse event monitoring or advertising and marketing enforcement. Nor are they assessed for generic drugs, medical devices, food importation or cosmetics. So, for almost a decade, the FDA has been forced to beg, borrow and steal staff and resources, robbing Peter to pay Paul, to the detriment of other vital agency operations. With the dangers of Mad Cow disease, bioterrorism, and bioengineered foods looming in our future, the agency cannot possibly meet its mandate with insufficient resources! Our nation is poised for a public health disaster because the FDA simply cannot do its job. Congress must adequately fund the FDA or institute user fees for all other areas of FDA's public health responsibilities.

User fees have enabled the FDA to cut new drug approval times in half, but they have also created a financial dependence by the agency on the industry it regulates. Understandably, the pharmaceutical industry wants to continue the user fee program. Every day that the industry can save on the new drug approval process is one more day they can sell their drug before their patents expire. However, the FDA's dependence on the user fees that companies pay creates a perceived conflict of interest that may compromise the health of the American public.

The integrity of the US drug approval process is at risk, and the implications of the loss of public trust here and around the world are immense. The FDA should not have a direct fiscal interest in optimizing user fees, because this practice has led to public distrust. Speaking for myself, I would think twice before being one of the first patients to take a newly marketed drug. I cannot trust that FDA reviewers in a "sweat shop atmosphere" adequately reviewed the product.

The only drugs given priority review at the agency should be treatments for life-threatening and untreatable diseases, drugs for patients who are not helped by existing treatments, or drugs for serious diseases that are safer or more effective than current therapies. In fact, we would recommend that you examine the FDA's definition of "clinical superiority" in the Orphan Drug Act regulations. Priority reviews should be given only to drugs that are substantially "different" from the drugs currently on the market and ones that have been clearly shown to be safer, or more effective, or to offer a significant contribution to patient care (e.g., an oral version of an injectable drug).

FDA's annual measure of success or failure should NOT be the number of drugs it approves during a given year, but rather the medical and public health advancements that each drug represents. The speedy approval of drugs for diagnoses that don't exist in medical texts, more cosmetic, "me-too," or lifestyle drugs, does not represent a major improvement in public health. Some drugs should take more time, and some should take less, depending on the quality of scientific data. Since the Reagan administration in the 1980s, the agency has had adequate tools to make investigational drugs available to patients who need them (e.g., compassionate use, treatment IND's, early access programs, etc.).

In summary, FDA needs more flexibility on spending user fees (they should not be confined to new drug reviews), and the onus is on Congress to either institute user fees for other industries, or appropriate sufficient funds for all of the other critically important public health responsibilities of the agency.

Pediatric Exclusivity

For rare diseases, the pediatric use of drugs that were developed for adult health conditions is an absolute necessity. Most children are healthy and may require the normal cough and cold remedies, antibiotics, and perhaps asthma drugs. Serious health conditions in children are rare, and medicines to treat their ailments are very rarely labeled with information about pediatric dosage.

NORD agrees that the pediatric exclusivity provision "has been highly effective in generating pediatric studies on many drugs and in providing useful new information in product labeling. We also agree with the proponents of the provision that it should be reauthorized by Congress in order to ensure that all children have access to medications needed to protect and preserve their health. But we feel that other types of incentives should be examined in the congressional debate, and careful fine-tuning of the law is needed.

We are delighted that the FDA has "drawn a line in the sand" against the industry's practice of enrolling healthy children in clinical trials, and it will no longer grant pediatric exclusivity if there is no potential benefit for children who participate in such studies. We say bravo to the FDA! The prohibition against including healthy children in clinical trials has been in effect since the 1970s (The Belmont Report), and it is part of the Common Rule and the Declaration of Helsinki. However, privately funded medical research does not have to obey the Common Rule, so for the past decade American children have been exposed to risks that are unacceptable in other industrialized nations of the world.

We believe there have been other unintended negative aspects of the pediatric exclusivity provision that should be addressed by this Congress.

• The Wall St. Journal reported that six months of pediatric exclusivity for the antihistamine Claritin amounts to $975 million dollars in sales to the manufacturer, six months of the antidepressant Prozac sales amounts to $831 million, while highly used generic drugs like the asthma compound Albuterol, and antibiotics like ampicillin, are not being studied in children at all.
• It is estimated that over 20 years of pediatric exclusivity will cost Americans $13.9 billion, while brand name drug makers will earn $29.6 billion, and generics will lose $10.7 billion. Distributors and pharmacies will lose $4.9 billion.  
• When FDA awards pediatric exclusivity, the exclusivity is awarded for the active moiety rather than just the pediatric indication. In one case a company studied an intravenous form of an indigestion drug on children, but the exclusivity applied to all liquid and pill forms, and even the over-the-counter version. Thus, the pediatric exclusivity provision is like a tax that Medicare-dependant grandparents have to pay for the sake of their grandchildren, by paying inflated prices for a longer period of time.
• Of the studies that have been done, and the exclusivity awarded, only a tiny proportion of those drugs have been re-labeled for pediatric usage. What use is a study when information about dosage adjustments and side effects is not available to pediatricians? We believe that exclusivity should NOT be awarded unless and until the label is actually changed.
• The law is inequitable because it leaves out huge categories of drugs (including biologics) that children need, that will never be studied. This includes generics and even patented drugs with small annual sales. The problem is that pediatric exclusivity encourages companies to study their most profitable drugs, but not the drugs that have the most intense medical need for children.
• Although we applaud the FDA's recent issuance of an interim rule providing additional safeguards for children in clinical trials, the pediatric exclusivity provision, as currently written, contains no human subject protections. Questions continue to be raised about clinical research in the pediatric population, as reports of large cash payments to parents and other questionably ethical inducements are reported in the press.
• The pediatric exclusivity provision actually bribes companies to do what they ought to be doing as decent corporate citizens. Until 1997, companies refused to conduct the studies until they saw a way to increase profits well in excess of what these studies cost. The FDA now says it will require all new drugs to be tested in children and can demand that trials be conducted when the agency feels a treatment will be applicable to children's diseases. However, drug companies are suing the FDA to stop this! The industry says the FDA has no authority to require companies to study their new drugs on children. We ask Congress to give the FDA this authority so the agency can protect the health and welfare of our children. It is regrettable that the government must force the industry to be good corporate citizens - a very sad state of affairs indeed.
• We also suggest that in the congressional debate about reauthorization of the pediatric exclusivity rule, you look at other options that will not tax the elderly with high drug prices, for the sake of the young. For example, instead of preventing lower cost generic drugs from reaching the market when brand name patents expire, why not award a large tax credit to companies that perform the clinical trials necessary for pediatric labeling? Perhaps a tax credit of 125 percent of the costs of the studies would entice companies into supporting the trials, and even reward generic companies who do pediatric investigations on older drugs. In fact, Congress' highest priority should be the development of incentives, or appropriation of funds, to encourage pediatric research on the generic drugs most needed by children.

In summary, Mr. Chairman, the FDA is losing the public's trust because it does not have the resources to do its job. The strict deadlines for new drug reviews are forcing drugs out on the market before FDA scientists adequately review them. Companies that do not feel their drugs are reviewed properly resort to lobbying Congress. There ought to be a firewall between industry and the FDA so that scientists can make their decisions based solely on scientific grounds. Yes, the FDA should be accountable, but so should the pharmaceutical industry. Drastically limiting review times while expecting more drugs to get approved is not the right way to measure success: It is a prescription for disaster.

We ask Congress to take a very careful look at the law and recognize that FDA's primary role is to protect and enhance the public's health. A more careful new drug review process will do much to avoid public health disasters in the future. FDA has had adequate mechanisms to allow very promising new drugs to reach the public before they are approved for marketing, but this should only be for life-threatening and serious diseases with no other treatment alternatives. We should not be rushing baldness remedies and indigestion drugs to market.

We also ask Congress to appropriate sufficient funds for other FDA initiatives. It has been reported that funding for non-PDUFA programs is down 20 percent, while PDUFA-related programs have seen increases of 27 percent. The exaggerated emphasis on new drug approvals saps resources from the agency's other public health functions.

Mr. Chairman, people with rare diseases desperately need new drugs to save their lives and prevent disability, but not at the expense of safety and efficacy. When we spend our hard earned money on a treatment, we want to know first if it is safe, and second if it is effective. Nothing else matters. Those with very serious and deadly illnesses are often willing to take higher risks (e.g., cancer chemotherapy drugs), but only if our doctors know what the side effects are and how to manage them. Our lives depend on the FDA, and if the agency cannot do its job, it puts our lives in jeopardy. We trust that Congress will use its wisdom to bring credibility back to FDA and bolster its public health mandate.

I thank the committee for its invitation to express the interests of people with rare diseases in the debate about reauthorization of FDAMA, including PDUFA and pediatric exclusivity.

References

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