Perspective
A To-Do List for the New FDA Commissioner
N Engl J Med 2009; 360:1373-1378April 2, 2009
- Article
A week before President Barack Obama's inauguration, the departing commissioner of the Food and Drug Administration (FDA), oncologist Andrew von Eschenbach, compared the agency he has led for the past 3 years to a person with cancer. Responding to a new report critical of the FDA, von Eschenbach said, “It is a great shock and surprise when someone says you have cancer. . . . The truth of the matter is that the process has been going on for a long time before it becomes apparent.”
Von Eschenbach's metaphor, although startling, was apt: the new commissioner of the FDA will take over an agency with serious systemic problems that urgently need to be addressed. In recent years, various reports have portrayed an FDA burdened by ever-expanding responsibilities in the face of a mostly flat annual budget, much of which comes from fees paid by the industries the agency regulates. For more than half of the past decade, the FDA has lacked a congressionally confirmed leader. A 2007 report prepared for the FDA Science Board concluded that the agency “cannot fulfill its mission” to ensure that the foods, drugs, medical devices, vaccines, and other products that it regulates are safe and effective, because it lacks modern scientific expertise, is critically underfunded and understaffed, and has a dangerously outmoded information-technology infrastructure.2 Testifying last year before a House subcommittee, Science Board chair Gail Cassell said, “We conclude that American lives are at risk and that there is an urgent need to address the deficiencies.” A series of high-profile incidents — related to the FDA's handling of information about the risks associated with drugs such as rofecoxib and antidepressants; the adulteration or contamination of imported ingredients in heparin, pet food, and other products; the agency's politically motivated delay in approving over-the-counter access to “Plan B” emergency contraception; and a series of major food-poisoning outbreaks — have damaged the FDA's credibility. It is perceived as slow to act, secretive, and subject to influence by political and corporate interests.
The FDA's portfolio is vast. It is responsible for licensing new medicines, monitoring the safety of those on the market, and ensuring the safety of about 80% of the country's food supply. It also regulates medical devices used for diagnosis, surgical implantation, and treatment; dietary supplements; biologics such as vaccines and cell-based or tissue-based therapies; the blood supply; radiation-emitting products, such as cell phones, computer monitors, and microwave ovens; cosmetics; and drugs and feed for animals — all in all, products accounting for about one quarter of annual spending by U.S. consumers. And tobacco products may soon be added to that list. With increasing globalization, ensuring safety requires the FDA to monitor ingredients and processes in factories located overseas. And advances in genetic engineering and genomics, nanotechnology, robotics, stem-cell biology, and other fields raise unprecedented regulatory challenges that require expertise and decision making in new areas of science.
The FDA's problems have prompted calls for restructuring, including proposals to remove it from the Department of Health and Human Services (DHHS) and elevate it to Cabinet-level status, to make the position of the commissioner a 6-year appointment (not subject to curtailing by the president except in cases of misconduct), to split off responsibility for food safety, perhaps into a new federal agency, and to separate drug-safety research and monitoring activities from the FDA branch responsible for approving new drugs.
With so many challenges, how much can a new commissioner expect to accomplish? “I think the right commissioner can do, actually, quite a lot,” said Donald Kennedy, who served as FDA commissioner under President Jimmy Carter in the 1970s. The commissioner has legal authority to take actions to protect the public health and has considerable power to make administrative changes without congressional action. Equally important, by communicating enthusiasm and clarity about the agency's mission, a strong commissioner “gives people who work at the FDA a sense of pride in what they're doing,” said Kennedy.
Even before being confirmed, the nominee for commissioner should meet with senators from both parties to begin the process of rebuilding the agency, writes former FDA official Virginia Cox in a book that was reportedly heavily consulted by the Obama transition team.3 The nominee “can begin focusing on key priorities, such as securing more federal funding,” Cox suggests. The FDA's Science Board estimated in its 2007 report that the agency's budget, then about $2 billion (now $2.4 billion), needed to more than double in order for it to carry out its current responsibilities. More than 40% of the FDA's workforce of approximately 10,000 is over 50 years of age; new employees must be recruited and trained to fill hundreds of vacancies, and staffing must be expanded in critical areas. And the agency's obsolete information-technology system must be replaced with one that allows it to collect, manage, and study essential data.
The new commissioner's ability to change the tone and to restore credibility will be critical both to obtaining needed resources from Congress and to carrying out internal reform, said Susan Wood, a professor of health policy at the George Washington University School of Public Health and Health Services. “Trust in the agency is at an all-time low,” said Wood, who resigned as assistant FDA commissioner for women's health in 2005 over the agency's refusal to follow its scientists' recommendations to approve Plan B. “The sea change can happen in the other direction, but it will take time.”
Wood and others emphasized the need to restore the preeminence of science in FDA decisions and to encourage debate and intellectual exchange within the agency, whose culture in recent years has reportedly discouraged dissent. In the wake of a highly critical 2006 Institute of Medicine report on drug safety, the FDA has instructed managers “to make sure we absolutely listen to everyone and document their opinions,” one employee said. But changing office culture takes longer in a federal agency than in a private company, where employees can more easily be fired, said consumer advocate Diana Zuckerman, president of the National Research Center for Women and Families.
President Obama has pledged that transparency will be a watchword of his administration, and Congress has already set the stage for greater transparency at the FDA. The 2007 Food and Drug Administration Amendments Act made several moves toward greater openness, one of the most important of which was requiring makers of drugs and medical devices to submit to a public database (ClinicalTrials.gov) the results of all studies (except preliminary safety studies) that they have conducted on approved drugs and devices — including studies with negative outcomes and those conducted in support of new indications for an approved product. That provision signals a shift from the agency's past position that most data it receives from manufacturers are proprietary.
Nevertheless, the FDA faces major obstacles as it struggles to do its job. Globalization has affected its ability to carry out many responsibilities, from ensuring product safety to monitoring the scientific and ethical integrity of clinical trials. For example, the agency inspects only about 1% of imported fresh produce and seafood, and it has no authority to hold importers legally accountable for unsafe food products. Although it has the authority to inspect overseas plants that make drugs marketed in the United States, it lacks an up-to-date registry of such plants and probably inspects no more than 8% of them in a given year.4 Moreover, even inspections would be unlikely to detect deliberate fraud like that in the recent case of adulteration of heparin ingredients imported from China.
Recently, an ongoing multistate salmonella outbreak led President Obama to promise a complete review of food-safety operations at the FDA. Currently, aspects of food regulation are carried out in three different parts of the agency, and at least 11 other federal agencies are also involved in food safety. The White House has promised a stricter regulatory structure, which might start with the consolidation of the FDA's food-related activities under a single official who would report directly to the DHHS secretary. Safeguarding the food supply will also require increased funding, as well as congressional action to update food-safety laws and to give the agency greater authority to order recalls and penalize purveyors of unsafe products.
The FDA's handling of medical device approvals also needs improvement. The 1976 law granting the agency authority to regulate medical devices allows it to approve certain new devices without clinical testing of safety and efficacy, provided they are deemed substantially equivalent to devices already on the market. Despite 1990 legislation ordering the agency to begin requiring more extensive clinical studies of class III devices (those implanted in the body) before approval, most are still approved with minimal testing.5 An “improved” pacemaker wire that was approved in this manner recently caused deaths when it fractured after being implanted in patients.
Regarding drugs, the FDA must continue to focus on striking the right balance between safety and efficacy and on promptly sharing emerging safety concerns with doctors and the public. There is consensus on the need for companies to conduct more postmarketing studies of newly approved medicines to look for adverse effects and measure long-term effectiveness, and the FDA has begun working with organizations that maintain large databases of information on patients to establish the Sentinel System, in which a drug's safety profile can be efficiently evaluated by epidemiologists. The goal is to have 25 million records available for such studies by 2010, an FDA official said.
Although commissioners often take on the job because they are interested in a specific issue, fixing the FDA will require a leader who is passionate about the agency and its mission as a whole. By restoring science to its rightful status, by forcefully advocating for needed resources, and by improving the FDA's record as a guardian of public health, the new commissioner will most effectively serve the American people.
Made in Manhattan — A Public Health Leader for the FDA
Dr. Margaret Hamburg, President Barack Obama's nominee for commissioner of the Food and Drug Administration (FDA), is an experienced public servant who has excelled in various jobs in the federal government and the nonprofit sector. But it was her 6 years as New York City health commissioner during the 1990s that presented the greatest challenges to her leadership, political skills, and ability to make tough public health decisions. Friends and colleagues say the New York health department was Hamburg's crucible — and that her tenure there provided ideal training for the FDA post.
At 35, Hamburg was the youngest finalist for the New York position, an internist and former federal health official who had served just 1 year in the health department when Mayor David Dinkins tapped her in 1991 as health commissioner. Hamburg was ambivalent about accepting the job, recalled Janny Scott, a New York Times reporter and Hamburg's longtime friend. The department was in the midst of a fiscal crisis, morale was abysmal, and employees were leaving in droves. Dinkins said he took a chance in choosing her: a city law required that the commissioner have a master's degree in public health, which Hamburg lacked. “I was able to get the city council to amend that law,” he recalled. Some public health lobbyists reacted with outrage, claiming she was unqualified. “Well, she proved them wrong in about 36 hours,” chuckled John W. Rowe, a professor of health policy and management at Columbia University's Mailman School of Public Health.
Dinkins credits Hamburg with persuading him to support needle-exchange programs in New York to slow the spread of HIV among drug addicts. “I said, `You've got to be kidding,'” he recalled. But Hamburg marshaled scientific evidence to convince him that such an initiative would both reduce HIV transmission and afford opportunities to enroll more addicts in drug-abuse treatment programs. “And it absolutely reduced the spread of AIDS,” Dinkins added.
But the biggest, most politically and socially complex public health crisis that Hamburg faced as commissioner was an epidemic of multidrug-resistant tuberculosis in the early 1990s. Hamburg successfully lobbied the city government for increased resources for tuberculosis control, including the hiring of a cadre of public health workers to go out daily into neighborhoods and watch patients take their medicines. Health department officials worked with hospitals to improve infection control and case finding; the department also worked to change the way shelters housed the homeless and persuaded prison officials to improve the screening of prisoners and to isolate inmates with active disease. And Hamburg communicated calmly and clearly with the public, reassuring New Yorkers who were afraid to ride the subway or send their children to public schools, recalled Rowe, who at the time was president of New York's Mount Sinai Medical Center. “The impression people got was that it was a steady hand on the tiller,” he recalled. Between 1992 and 1994, these efforts achieved a 21% reduction in reported tuberculosis cases.
In her handling of the epidemic, Hamburg displayed the qualities needed to run the FDA, Rowe said. “She provided clear evidence that she understood public health, she understood how a health system works, she understood medical science and how to develop an evidence-based strategy, she understood how to run a large organization, and she understood how to deal with the public” and with political controversy.
Hamburg's upbringing may have predestined her for a life in medicine and public service. Her parents, David and Beatrix Hamburg, are preeminent psychiatrists whose careers have combined academic medicine, mental illness research, and leadership in public policy and philanthropy. David Hamburg is a past president of the Carnegie Corporation and of the Institute of Medicine; Beatrix Hamburg is a past president of the William T. Grant Foundation and was the first black woman to attend Vassar College and to earn a degree from the Yale University School of Medicine. Hamburg grew up on the campus of Stanford University, where her parents were faculty members, and had extraordinary opportunities, including an internship as a teenager with Jane Goodall studying chimpanzees in Tanzania, recalled her friend Janny Scott.
Scott describes Hamburg as independent and confident, albeit naturally reticent. “She is the last person to overtly blow her own horn,” she said, adding, “She's completely unflappable; I don't know that I've ever seen her really rattled. . . . She reminds me a little of an Obama kind of person — very low-drama, highly competent.”
After completing college and medical school at Harvard and residency at New York Hospital–Cornell Medical Center, Hamburg held several positions in the Department of Health and Human Services (DHHS), including serving as special assistant to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases during the late 1980s, an assignment that taught her much about the science and politics of drug regulation. “She was right there by my side when we were fighting the battles of getting approval of the early HIV drugs,” weighing evidence from clinical trials and responding to demands from AIDS advocacy groups that new drugs be made available on a compassionate basis before approval, Fauci recalled. Hamburg's extensive DHHS experience — including 3 years as assistant secretary for planning and evaluation under President Bill Clinton, during which she focused on public health preparedness and emerging infections — schooled her in the workings of the federal government.
Since 2001, Hamburg has been a bioterrorism expert with the Nuclear Threat Initiative's Global Health and Security Initiative, a Washington think tank that focuses on threats to health and security. She has also served on numerous expert committees and boards, mostly for nonprofit organizations and federal government agencies, including the Centers for Disease Control and Prevention, the Defense Department, the Central Intelligence Agency, and the Office of the Director of National Intelligence. Her curriculum vitae states that she currently serves on the board of directors of Henry Schein, a private company that distributes medical supplies, including pharmaceuticals and vaccines — apparently a paid position, and one that presumably would pose a conflict of interest for an FDA commissioner.
But longtime colleagues of Hamburg praise her integrity, intelligence, and passion for public health. As FDA commissioner, “You have to absorb huge amounts of information. You have to know what to ask for. You have to be able to distinguish what matters. And you have to be able to come to clear decisions,” said Harvey Fineberg, president of the Institute of Medicine. “She's got all of those qualities.”
An Activist for Deputy FDA Commissioner
Dr. Joshua M. Sharfstein, whom President Barack Obama has appointed as deputy commissioner of the Food and Drug Administration (FDA), is an energetic city health commissioner with an activist's approach to health policy. Colleagues describe the pediatrician as a smart, principled problem solver who combines a flair for political strategy and alliance building, honed as a congressional aide, with a willingness to pick a fight when necessary to achieve his aim.
After Obama's election, Sharfstein (who is 39 years old) headed the administration's transition team for the FDA, a job that afforded him an inside look at the beleaguered agency as well as a chance to hear from outside critics about how to reform it. He combines an insider's knowledge of Washington, acquired during his 4 1/2 years working on health issues for Representative Henry Waxman (D-CA), with a productive tenure as commissioner of health for the city of Baltimore, a job he has held since December 2005. In Baltimore, he led a successful campaign to get the FDA to tighten its regulation of over-the-counter use of cold medicines in children, expanded access to substance-abuse programs in the city, fought for the recently implemented ban on smoking in Baltimore's bars and restaurants, and sought to help the city's seniors and low-income residents obtain coverage for prescription drugs under Medicare Part D or local drug-assistance programs.
Sharfstein has been adept at enlisting allies from academia, government agencies, and organized medicine to achieve his goals, said Michael Klag, dean of the Johns Hopkins Bloomberg School of Public Health. For example, when Hopkins researchers released a study highlighting the lack of healthy food choices in inner-city Baltimore, the health commissioner was caught off guard. “Some people would have gotten angry” about the lack of advance warning, Klag said. Instead, Sharfstein responded by arranging for his office to receive regular updates about ongoing public health research in the city. Although he had not previously worked as a manager, he has effectively run an agency with 1000 employees and a $200 million annual budget, Klag added. “He is a nuts-and-bolts guy. He gets under the hood and makes the system work.”
The son of two physicians, a nationally prominent psychiatrist and a pediatrician, Sharfstein volunteered for political campaigns as a college student, and by the time he entered Harvard Medical School, he was already focusing on health policy: for example, he published an article taking the American Medical Association to task for supporting political candidates who opposed its own public health positions. As a pediatric resident at Boston's Children's Hospital and Boston Medical Center, he spearheaded opposition to the funding of residency events by pharmaceutical companies and participated in a resident-led project linking illnesses and injuries in poor urban children to inadequate housing. Sharfstein also worked on the issue of access to mental health treatment during a stint at Public Citizen's Health Research Group in Washington, DC, and later during a postresidency fellowship year at Boston University. As an aide to Waxman, one of his tasks was developing legislation to give the FDA authority to regulate tobacco products.
Friends and colleagues say that Sharfstein is a quick study, and that his Capitol Hill experience and public health background will be valuable assets at the FDA. Barry Zuckerman, chair of pediatrics at Boston University School of Medicine and a longtime mentor, said his former resident Sharfstein “can solve problems better than anyone I know. He will figure out the strategies to be effective.”
No potential conflict of interest relevant to this article was reported.
This article (10.1056/NEJMp0810755) was published at NEJM.org on March 14, 2009.
Source Information
Dr. Okie is a national correspondent for the Journal.
- References
References
1
Harris G. Report criticizes F.D.A. on device testing. New York Times. January 16, 2009:A15.
2
FDA Science Board. FDA science and mission at risk: report of the Subcommittee on Science and Technology. Bethesda, MD: Food and Drug Administration, November 2007.
3
Green M, Jolin M, eds. Change for America: a progressive blueprint for the 44th president. New York: Basic Books, 2009.
4
Drug safety: better data management and more inspections are needed to strengthen FDA's foreign drug inspection program. Washington, DC: Government Accountability Office, September 2008. (Publication no. GAO-08-970.)
5
Medical devices: FDA should take steps to ensure that high-risk device types are approved through the most stringent premarket review process. Washington, DC: Government Accountability Office, January 2009. (Publication no. GAO-09-190.)
- Citing Articles (1)
Citing Articles
1
(2009) Ethical and Scientific Implications of the Globalization of Clinical Research. New England Journal of Medicine 360:26, 2792-2793
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