NERVECENTER November 2013
© robtek | Shutterstock.com
The idea of a user fee was controversial from the start. Concerns were voiced that the FDA would now become a customer of the pharmaceutical industry instead of a regulator. “It is very rare that the regulated industry paying user fees is able to negotiate the terms of the work, put restrictions on that work and how the funds from the fees will be spent,” says Susan F. Wood, PhD, Associate Professor and Director of the Jacobs Institute
Controversy Still Swirls Around
FDA User Fees SINCE 1992, THE PRESCRIPTION DRUG USER FEE ACT AND REAUTHORIZATIONS HAVE SPED UP NEW DRUG APPROVALS— BUT DOES SPEED EQUAL SAFETY?
In 1992, the US Congress first passed the Prescription Drug User Fee Act (PDUFA) giving the US Food and Drug Administration (FDA) additional resources to speed up approvals of New Drug Applications. Every five years since, the law has been revisited and reauthorized. The last time was in 2012. “Prior to PDUFA, there was increasing concern that inadequate resources at the FDA were contributing to very long drug application review times,” says Kenneth I. Kaitin, PhD, Director of the Tufts University Center for the Study of Drug Development in Boston, Massachusetts. “The AIDS epidemic catalyzed efforts to give the FDA added resources, allowing it to function more efficiently and get products to market quicker.” A10
Fee Collection and Quicker Decisions One method to address this issue was instituting a user fee whereby pharmaceutical companies would pay for the resources needed to expedite drug approvals. The 1992 Act included language requiring Congress to meet a certain level of FDA funding, or industry could stop paying the fees. At the same time, the FDA committed to reduce the time it took to reach a decision on medications to as little as six months for medications representing important therapeutic gains. However, this did not mean that the FDA would approve drugs in that timeframe—the response could be approval, request for more information, or rejection.
In the real world, Congress hasn’t given the FDA what they need to fulfill their mission. —Kenneth I. Kaitin, PhD of Women’s Health at the George Washington University School of Public Health and Health Services in Washington, DC. “The two key issues raised are who controls how the money is spent and who is the FDA working for if most of their resources come from the industry?”
Approval Times Drop from Three Years to Around One At least on the surface, user fees appear to be working. Approval of medications that took three or more years before PDUFA now average just over a year. The US used to lag behind in Europe and Japan, but now is often the first country where a drug is marketed. While some express concerns, others think this is a good thing. “When there are limited or no treatments available for diseases where morbidity and mortality are high (for example, Alzheimer and Parkinson disease), patients and their families tend to accept a greater degree of risk in new drug approvals, with the hope of getting earlier access to potentially breakthrough medicines,” says Dr. Kaitin. Before each of the five-year reauthorizations since 1992, the FDA sits down with industry representatives and negotiates the terms of the work, restrictions on that work, and the amount of funding. This is submitted to Congress for approval, and has usually November 2013
• NERVECENTER It is important to prescribers that the FDA is strong and independent so they can trust the information they are getting is correct and based on the best judgment of the FDA’s scientists and physicians. — Susan F. Wood, PhD circumstances. Dr. Kaitin counters that you will have many millions more who benefit from earlier access to medications.
Too Much Focus on Approvals
Conflicts of Interest? “There is a conflict of interest when the regulated entities supply funds that pay the salaries of regulators,” says Aaron S. Kesselheim, MD, JD, Assistant Professor of Medicine at the Harvard Medical School in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. Both Drs. Wood and Kesselheim point to studies by Daniel Carpenter at Harvard and Mary Olsen at Tulane as reasons for their concerns. They found that drugs approved near FDA review deadlines were more often associated with subsequent safety issues than drugs approved at other times. However, Dr. Kaitin does not see this as a concern. “Our research, and that of the FDA, shows that if you look at the number of medications removed from the market based on the year of approval and as a percentage of total approvals, it remains remarkably stable,” he says. “It hasn’t changed much, staying at roughly 1% or 2% across time.” This is a graphic illustration of the balancing act seen when discussing medication approvals. Dr. Kesselheim suggests that approving more medications on the basis of limited data of efficacy and safety exposes patients to adverse events without benefit and should be reserved for only life-threatening Volume 74, No. 5
There is a conflict of interest when the regulated entities supply funds that pay the salaries of regulators. — Aaron S. Kesselheim, MD, JD
“The deadlines ended up sucking up resources from elsewhere in the agency,” says Dr. Wood. “More recent reauthorizations have loosened this up somewhat, but there is still a lack of needed resources in other areas.”
Who Should Pay and How Much Control? Basically, the controversy boils down to who should be paying for what and the degree of control wielded by those paying the user fees. “In my ideal world, [the drug approval process] would be publicly supported so that the industry would have no say in how the money is spent,” says Dr. Wood. “Even if it has to be privately funded, the FDA, with direction from Congress, should be able to use
says. “Every five years there is mandatory reform of the FDA.” The debate about user fees is likely to continue. “The FDA is a place unto itself in the government,” says Dr. Wood. “It doesn’t fund research like the National Institutes of Health or monitor health issues like the Centers for Disease Control and Prevention. It is important to prescribers that the FDA is strong and independent so they can trust the information they are getting is correct and based on the best judgment of the FDA’s scientists and physicians.” •
been passed with some modifications and changes. This leads to concerns that the FDA is essentially “captured” by those they regulate, especially as user fees became an increasingly important part of the budget.
Input from the pharmaceutical industry on where the user fee money will be spent has led, in the view of some, to focusing resources on approval. This may be to the detriment of other priorities, such as postmarket surveillance and oversight of overseas studies. Recent reauthorizations have addressed this concern to some extent. The scarcity of resources may have been made worse by user fees for biologics, medical devices, and generic drugs. To the extent user fees don’t cover the costs needed to meet deadlines for these reviews, other important areas may suffer.
those funds as they see fit.” Dr. Kaitin agrees that in a perfect world, PUDFA and its reauthorizations would not be needed. However, that is not current reality. “In the real world, Congress hasn’t given the FDA what they need to fulfill their mission,” says Dr. Kaitin. “This was, I think, a very appropriate way to resolve that issue.” Dr. Kaitin suggests that the real strength of the PUDFA lies in revisiting user fees and the FDA on a regular basis. He feels this allows a structured review of the FDA instead of the crisis-oriented approach seen in the past. “With each new reiteration, there have been changes to the FDA that not only reflect a desire to improve processes, but also the changing sentiments of the public,” he
KURT ULLMAN DOI: 10.1002/ana.24045
A11
© robtek | Shutterstock.com
The idea of a user fee was controversial from the start. Concerns were voiced that the FDA would now become a customer of the pharmaceutical industry instead of a regulator. “It is very rare that the regulated industry paying user fees is able to negotiate the terms of the work, put restrictions on that work and how the funds from the fees will be spent,” says Susan F. Wood, PhD, Associate Professor and Director of the Jacobs Institute
Controversy Still Swirls Around
FDA User Fees SINCE 1992, THE PRESCRIPTION DRUG USER FEE ACT AND REAUTHORIZATIONS HAVE SPED UP NEW DRUG APPROVALS— BUT DOES SPEED EQUAL SAFETY?
In 1992, the US Congress first passed the Prescription Drug User Fee Act (PDUFA) giving the US Food and Drug Administration (FDA) additional resources to speed up approvals of New Drug Applications. Every five years since, the law has been revisited and reauthorized. The last time was in 2012. “Prior to PDUFA, there was increasing concern that inadequate resources at the FDA were contributing to very long drug application review times,” says Kenneth I. Kaitin, PhD, Director of the Tufts University Center for the Study of Drug Development in Boston, Massachusetts. “The AIDS epidemic catalyzed efforts to give the FDA added resources, allowing it to function more efficiently and get products to market quicker.” A10
Fee Collection and Quicker Decisions One method to address this issue was instituting a user fee whereby pharmaceutical companies would pay for the resources needed to expedite drug approvals. The 1992 Act included language requiring Congress to meet a certain level of FDA funding, or industry could stop paying the fees. At the same time, the FDA committed to reduce the time it took to reach a decision on medications to as little as six months for medications representing important therapeutic gains. However, this did not mean that the FDA would approve drugs in that timeframe—the response could be approval, request for more information, or rejection.
In the real world, Congress hasn’t given the FDA what they need to fulfill their mission. —Kenneth I. Kaitin, PhD of Women’s Health at the George Washington University School of Public Health and Health Services in Washington, DC. “The two key issues raised are who controls how the money is spent and who is the FDA working for if most of their resources come from the industry?”
Approval Times Drop from Three Years to Around One At least on the surface, user fees appear to be working. Approval of medications that took three or more years before PDUFA now average just over a year. The US used to lag behind in Europe and Japan, but now is often the first country where a drug is marketed. While some express concerns, others think this is a good thing. “When there are limited or no treatments available for diseases where morbidity and mortality are high (for example, Alzheimer and Parkinson disease), patients and their families tend to accept a greater degree of risk in new drug approvals, with the hope of getting earlier access to potentially breakthrough medicines,” says Dr. Kaitin. Before each of the five-year reauthorizations since 1992, the FDA sits down with industry representatives and negotiates the terms of the work, restrictions on that work, and the amount of funding. This is submitted to Congress for approval, and has usually November 2013
• NERVECENTER It is important to prescribers that the FDA is strong and independent so they can trust the information they are getting is correct and based on the best judgment of the FDA’s scientists and physicians. — Susan F. Wood, PhD circumstances. Dr. Kaitin counters that you will have many millions more who benefit from earlier access to medications.
Too Much Focus on Approvals
Conflicts of Interest? “There is a conflict of interest when the regulated entities supply funds that pay the salaries of regulators,” says Aaron S. Kesselheim, MD, JD, Assistant Professor of Medicine at the Harvard Medical School in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. Both Drs. Wood and Kesselheim point to studies by Daniel Carpenter at Harvard and Mary Olsen at Tulane as reasons for their concerns. They found that drugs approved near FDA review deadlines were more often associated with subsequent safety issues than drugs approved at other times. However, Dr. Kaitin does not see this as a concern. “Our research, and that of the FDA, shows that if you look at the number of medications removed from the market based on the year of approval and as a percentage of total approvals, it remains remarkably stable,” he says. “It hasn’t changed much, staying at roughly 1% or 2% across time.” This is a graphic illustration of the balancing act seen when discussing medication approvals. Dr. Kesselheim suggests that approving more medications on the basis of limited data of efficacy and safety exposes patients to adverse events without benefit and should be reserved for only life-threatening Volume 74, No. 5
There is a conflict of interest when the regulated entities supply funds that pay the salaries of regulators. — Aaron S. Kesselheim, MD, JD
“The deadlines ended up sucking up resources from elsewhere in the agency,” says Dr. Wood. “More recent reauthorizations have loosened this up somewhat, but there is still a lack of needed resources in other areas.”
Who Should Pay and How Much Control? Basically, the controversy boils down to who should be paying for what and the degree of control wielded by those paying the user fees. “In my ideal world, [the drug approval process] would be publicly supported so that the industry would have no say in how the money is spent,” says Dr. Wood. “Even if it has to be privately funded, the FDA, with direction from Congress, should be able to use
says. “Every five years there is mandatory reform of the FDA.” The debate about user fees is likely to continue. “The FDA is a place unto itself in the government,” says Dr. Wood. “It doesn’t fund research like the National Institutes of Health or monitor health issues like the Centers for Disease Control and Prevention. It is important to prescribers that the FDA is strong and independent so they can trust the information they are getting is correct and based on the best judgment of the FDA’s scientists and physicians.” •
been passed with some modifications and changes. This leads to concerns that the FDA is essentially “captured” by those they regulate, especially as user fees became an increasingly important part of the budget.
Input from the pharmaceutical industry on where the user fee money will be spent has led, in the view of some, to focusing resources on approval. This may be to the detriment of other priorities, such as postmarket surveillance and oversight of overseas studies. Recent reauthorizations have addressed this concern to some extent. The scarcity of resources may have been made worse by user fees for biologics, medical devices, and generic drugs. To the extent user fees don’t cover the costs needed to meet deadlines for these reviews, other important areas may suffer.
those funds as they see fit.” Dr. Kaitin agrees that in a perfect world, PUDFA and its reauthorizations would not be needed. However, that is not current reality. “In the real world, Congress hasn’t given the FDA what they need to fulfill their mission,” says Dr. Kaitin. “This was, I think, a very appropriate way to resolve that issue.” Dr. Kaitin suggests that the real strength of the PUDFA lies in revisiting user fees and the FDA on a regular basis. He feels this allows a structured review of the FDA instead of the crisis-oriented approach seen in the past. “With each new reiteration, there have been changes to the FDA that not only reflect a desire to improve processes, but also the changing sentiments of the public,” he
KURT ULLMAN DOI: 10.1002/ana.24045
A11
