Perspective April 2, 2009

The NEW ENGLAND JOURNAL of MEDICINE

Perspective april 2, 2009

A To-Do List for the New FDA Commissioner Susan Okie, M.D.

week before President Barack Obama’s inaugu- dress the deficiencies.” A series of ration, the departing commissioner of the high-profile incidents — related A to the FDA’s handling of informa- Food and Drug Administration (FDA), oncologist tion about the risks associated Andrew von Eschenbach, compared the agency he with drugs such as rofecoxib and antidepressants; the adulteration has led for the past 3 years to a fees paid by the industries the or contamination of imported in- person with cancer. Responding agency regulates. For more than gredients in heparin, pet food, and to a new report critical of the FDA, half of the past decade, the FDA other products; the agency’s po- von Eschenbach said, “It is a great has lacked a congressionally con- litically motivated delay in approv- shock and surprise when someone firmed leader. A 2007 report pre- ing over-the-counter access to says you have cancer. . . . The pared for the FDA Science Board “Plan B” emergency contraception; truth of the matter is that the concluded that the agency “cannot and a series of major food-poi- process has been going on for a fulfill its mission” to ensure that soning outbreaks — have dam- long time before it becomes ap- the foods, drugs, medical devices, aged the FDA’s credibility. It is per- parent.”1 vaccines, and other products that ceived as slow to act, secretive, and Von Eschenbach’s metaphor, it regulates are safe and effective, subject to influence by political although startling, was apt: the because it lacks modern scientific and corporate interests. new commissioner of the FDA will expertise, is critically underfund- The FDA’s portfolio is vast. It take over an agency with serious ed and understaffed, and has a is responsible for licensing new systemic problems that urgently dangerously outmoded informa- medicines, monitoring the safety need to be addressed. In recent tion-technology infrastructure.2 of those on the market, and ensur- years, various reports have por- Testifying last year before a House ing the safety of about 80% of the trayed an FDA burdened by ever- subcommittee, Science Board chair country’s food supply. It also reg- expanding responsibilities in the Gail Cassell said, “We conclude ulates medical devices used for face of a mostly flat annual bud- that American lives are at risk and diagnosis, surgical implantation, get, much of which comes from that there is an urgent need to ad- and treatment; dietary supple-

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Made in Manhattan — A Public Health Leader for the FDA r. Margaret Hamburg, Presi- led John W. Rowe, a professor of control and case finding; the de- Ddent Barack Obama’s nomi- health policy and management at partment also worked to change nee for commissioner of the Food Columbia University’s Mailman the way shelters housed the home- and Drug Administration (FDA), School of Public Health. less and persuaded prison offi- is an experienced public servant Dinkins credits Hamburg with cials to improve the screening of who has excelled in various jobs persuading him to support needle- prisoners and to isolate inmates in the federal government and the exchange programs in New York with active disease. And Hamburg nonprofit sector. But it was her to slow the spread of HIV among communicated calmly and clearly 6 years as New York City health drug addicts. “I said, ‘You’ve got with the public, reassuring New commissioner during the 1990s to be kidding,’” he recalled. But Yorkers who were afraid to ride that presented the greatest chal- Hamburg marshaled scientific evi- the subway or send their children lenges to her leadership, political dence to convince him that such to public schools, recalled Rowe, skills, and ability to make tough who at the time was president of public health decisions. Friends New York’s Mount Sinai Medical and colleagues say the New York Center. “The impression people health department was Hamburg’s got was that it was a steady hand crucible — and that her tenure on the tiller,” he recalled. Between there provided ideal training for 1992 and 1994, these efforts the FDA post. achieved a 21% reduction in re- At 35, Hamburg was the young- ported tuberculosis cases. est finalist for the New York posi- In her handling of the epidem- tion, an internist and former fed- ic, Hamburg displayed the quali- eral health official who had served ties needed to run the FDA, Rowe just 1 year in the health depart- said. “She provided clear evidence ment when Mayor David Dinkins an initiative would both reduce that she understood public health, tapped her in 1991 as health com- HIV transmission and afford op- she understood how a health sys- missioner. Hamburg was ambiva- portunities to enroll more addicts tem works, she understood med- lent about accepting the job, re- in drug-abuse treatment programs. ical science and how to develop called Janny Scott, a New York “And it absolutely reduced the an evidence-based strategy, she Times reporter and Hamburg’s spread of AIDS,” Dinkins added. understood how to run a large longtime friend. The department But the biggest, most politi- organization, and she understood was in the midst of a fiscal crisis, cally and socially complex public how to deal with the public” and morale was abysmal, and employ- health crisis that Hamburg faced with political controversy. ees were leaving in droves. Dinkins as commissioner was an epidem- Hamburg’s upbringing may said he took a chance in choos- ic of multidrug-resistant tubercu- have predestined her for a life in ing her: a city law required that losis in the early 1990s. Hamburg medicine and public service. Her the commissioner have a master’s successfully lobbied the city gov- parents, David and Beatrix Ham- degree in public health, which ernment for increased resources burg, are preeminent psychiatrists Hamburg lacked. “I was able to for tuberculosis control, includ- whose careers have combined get the city council to amend that ing the hiring of a cadre of public academic medicine, mental ill- law,” he recalled. Some public health workers to go out daily ness research, and leadership in health lobbyists reacted with out- into neighborhoods and watch pa- public policy and philanthropy. rage, claiming she was unquali- tients take their medicines. Health David Hamburg is a past presi- fied. “Well, she proved them department officials worked with dent of the Carnegie Corporation

wrong in about 36 hours,” chuck- hospitals to improve infection and of the Institute of Medicine; Getty Images

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Beatrix Hamburg is a past presi- Fauci recalled. Hamburg’s exten- ments; biologics such as vaccines dent of the William T. Grant Foun- sive DHHS experience — includ- and cell-based or tissue-based dation and was the first black ing 3 years as assistant secretary therapies; the blood supply; radi- woman to attend Vassar College for planning and evaluation un- ation-emitting products, such as and to earn a degree from the Yale der President Bill Clinton, during cell phones, computer monitors, University School of Medicine. which she focused on public and microwave ovens; cosmetics; and drugs and feed for animals Hamburg grew up on the cam- health preparedness and emerg- — all in all, products accounting pus of Stanford University, where ing infections — schooled her in for about one quarter of annual her parents were faculty members, the workings of the federal gov- spending by U.S. consumers. And and had extraordinary opportuni- ernment. tobacco products may soon be ties, including an internship as a Since 2001, Hamburg has been added to that list. With increas- teenager with Jane Goodall study- a bioterrorism expert with the ing globalization, ensuring safety ing chimpanzees in Tanzania, re- Nuclear Threat Initiative’s Global requires the FDA to monitor in- called her friend Janny Scott. Health and Security Initiative, a gredients and processes in facto- Scott describes Hamburg as Washington think tank that fo- ries located overseas. And advanc- independent and confident, albeit cuses on threats to health and es in genetic engineering and naturally reticent. “She is the last security. She has also served on genomics, nanotechnology, robot- person to overtly blow her own numerous expert committees and ics, stem-cell biology, and other fields raise unprecedented regula- horn,” she said, adding, “She’s boards, mostly for nonprofit orga- tory challenges that require ex- completely unflappable; I don’t nizations and federal government pertise and decision making in know that I’ve ever seen her re- agencies, including the Centers new areas of science. ally rattled. . . . She reminds me for Disease Control and Preven- The FDA’s problems have a little of an Obama kind of per- tion, the Defense Department, prompted calls for restructuring, son — very low-drama, highly the Central Intelligence Agency, including proposals to remove it competent.” and the Office of the Director of from the Department of Health After completing college and National Intelligence. Her curricu- and Human Services (DHHS) and medical school at Harvard and lum vitae states that she currently elevate it to Cabinet-level status, residency at New York Hospital– serves on the board of directors to make the position of the com- Cornell Medical Center, Ham- of Henry Schein, a private commissioner a 6-year appointment burg held several positions in the pany that distributes medical sup- (not subject to curtailing by the president except in cases of mis- Department of Health and Hu- plies, including pharmaceuticals conduct), to split off responsibil- man Services (DHHS), including and vaccines — apparently a paid ity for food safety, perhaps into a serving as special assistant to position, and one that presum- new federal agency, and to sepa- Anthony Fauci, director of the Na- ably would pose a conflict of inter- rate drug-safety research and mon tional Institute of Allergy and est for an FDA commissioner. itoring activities from the FDA Infectious Diseases during the But longtime colleagues of branch responsible for approving late 1980s, an assignment that Hamburg praise her integrity, in- new drugs. taught her much about the sci- telligence, and passion for public With so many challenges, how ence and politics of drug regula- health. As FDA commissioner, much can a new commissioner tion. “She was right there by my “You have to absorb huge amounts expect to accomplish? “I think the side when we were fighting the of information. You have to know right commissioner can do, ac- battles of getting approval of the what to ask for. You have to be tually, quite a lot,” said Donald Kennedy, who served as FDA com- early HIV drugs,” weighing evi- able to distinguish what matters. missioner under President Jimmy dence from clinical trials and re- And you have to be able to come Carter in the 1970s. The commis- sponding to demands from AIDS to clear decisions,” said Harvey sioner has legal authority to take advocacy groups that new drugs Fineberg, president of the Insti- actions to protect the public health be made available on a compas- tute of Medicine. “She’s got all of and has considerable power to sionate basis before approval, those qualities.” make administrative changes with-

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out congressional action. Equally ommendations to approve Plan B. do its job. Globalization has af- important, by communicating en- “The sea change can happen in fected its ability to carry out many thusiasm and clarity about the the other direction, but it will responsibilities, from ensuring agency’s mission, a strong com- take time.” product safety to monitoring the missioner “gives people who work Wood and others emphasized scientific and ethical integrity of at the FDA a sense of pride in what the need to restore the preemi- clinical trials. For example, the they’re doing,” said Kennedy. nence of science in FDA decisions agency inspects only about 1% of Even before being confirmed, and to encourage debate and intel- imported fresh produce and sea- the nominee for commissioner lectual exchange within the agen- food, and it has no authority to should meet with senators from cy, whose culture in recent years hold importers legally account- both parties to begin the process has reportedly discouraged dis- able for unsafe food products. Al- of rebuilding the agency, writes sent. In the wake of a highly criti- though it has the authority to in- former FDA official Virginia Cox cal 2006 Institute of Medicine re- spect overseas plants that make in a book that was reportedly port on drug safety, the FDA has drugs marketed in the United heavily consulted by the Obama instructed managers “to make States, it lacks an up-to-date reg- transition team.3 The nominee sure we absolutely listen to every- istry of such plants and probably “can begin focusing on key priori- one and document their opinions,” inspects no more than 8% of ties, such as securing more feder- one employee said. But changing them in a given year.4 Moreover, al funding,” Cox suggests. The office culture takes longer in a even inspections would be un- FDA’s Science Board estimated in federal agency than in a private likely to detect deliberate fraud its 2007 report that the agency’s company, where employees can like that in the recent case of budget, then about $2 billion (now more easily be fired, said consum- adulteration of heparin ingredi- $2.4 billion), needed to more than er advocate Diana Zuckerman, ents imported from China. double in order for it to carry out president of the National Research Recently, an ongoing multistate its current responsibilities. More Center for Women and Families. salmonella outbreak led President than 40% of the FDA’s workforce President Obama has pledged Obama to promise a complete re- of approximately 10,000 is over that transparency will be a watch- view of food-safety operations at 50 years of age; new employees word of his administration, and the FDA. Currently, aspects of food must be recruited and trained to Congress has already set the stage regulation are carried out in three fill hundreds of vacancies, and for greater transparency at the different parts of the agency, and staffing must be expanded in crit- FDA. The 2007 Food and Drug at least 11 other federal agencies ical areas. And the agency’s obso- Administration Amendments Act are also involved in food safety. lete information-technology system made several moves toward great- The White House has promised a must be replaced with one that er openness, one of the most im- stricter regulatory structure, which allows it to collect, manage, and portant of which was requiring might start with the consolidation study essential data. makers of drugs and medical de- of the FDA’s food-related activi- The new commissioner’s abil- vices to submit to a public data- ties under a single official who ity to change the tone and to re- base (ClinicalTrials.gov) the results would report directly to the DHHS store credibility will be critical of all studies (except preliminary secretary. Safeguarding the food both to obtaining needed resourc- safety studies) that they have con- supply will also require increased es from Congress and to carrying ducted on approved drugs and de- funding, as well as congressional out internal reform, said Susan vices — including studies with action to update food-safety laws Wood, a professor of health pol- negative outcomes and those con- and to give the agency greater au- icy at the George Washington Uni- ducted in support of new indica- thority to order recalls and penal- versity School of Public Health and tions for an approved product. ize purveyors of unsafe products. Health Services. “Trust in the That provision signals a shift from The FDA’s handling of medi- agency is at an all-time low,” said the agency’s past position that cal device approvals also needs Wood, who resigned as assistant most data it receives from man- improvement. The 1976 law grant- FDA commissioner for women’s ufacturers are proprietary. ing the agency authority to regu- health in 2005 over the agency’s Nevertheless, the FDA faces late medical devices allows it to refusal to follow its scientists’ rec- major obstacles as it struggles to approve certain new devices with-

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An Activist for Deputy FDA Commissioner r. Joshua M. Sharfstein, whom Sharfstein has been adept at The son of two physicians, a DPresident Barack Obama has enlisting allies from academia, nationally prominent psychiatrist appointed as deputy commission government agencies, and orga- and a pediatrician, Sharfstein vol- er of the Food and Drug Adminis- nized medicine to achieve his unteered for political campaigns tration (FDA), is an energetic city goals, said Michael Klag, dean of as a college student, and by the health commissioner with an ac- the Johns Hopkins Bloomberg time he entered Harvard Medical tivist’s approach to health policy. School of Public Health. For ex- School, he was already focusing Colleagues describe the pediatri- ample, when Hopkins research- on health policy: for example, he cian as a smart, principled prob- ers released a study highlighting published an article taking the lem solver who combines a flair the lack of healthy food choices American Medical Association to for political strategy and alliance task for supporting political can- building, honed as a congressio- didates who opposed its own pub- nal aide, with a willingness to pick lic health positions. As a pediatric a fight when necessary to achieve resident at Boston’s Children’s his aim. Hospital and Boston Medical Cen- After Obama’s election, Sharf- ter, he spearheaded opposition to stein (who is 39 years old) head- the funding of residency events ed the administration’s transition by pharmaceutical companies and team for the FDA, a job that af- participated in a resident-led proj- forded him an inside look at the ect linking illnesses and injuries beleaguered agency as well as a in poor urban children to inade- chance to hear from outside crit- quate housing. Sharfstein also ics about how to reform it. He worked on the issue of access to combines an insider’s knowledge mental health treatment during a of Washington, acquired during stint at Public Citizen’s Health his 4 1∕2 years working on health Research Group in Washington, issues for Representative Henry D.C., and later during a postresi- Waxman (D-CA), with a produc- dency fellowship year at Boston tive tenure as commissioner of in inner-city Baltimore, the health University. As an aide to Wax- health for the city of Baltimore, a commissioner was caught off man, one of his tasks was devel- job he has held since December guard. “Some people would have oping legislation to give the FDA 2005. In Baltimore, he led a suc- gotten angry” about the lack of authority to regulate tobacco cessful campaign to get the FDA advance warning, Klag said. In- products. to tighten its regulation of over- stead, Sharfstein responded by Friends and colleagues say that the-counter use of cold medicines arranging for his office to receive Sharfstein is a quick study, and in children, expanded access to regular updates about ongoing that his Capitol Hill experience and substance-abuse programs in the public health research in the city. public health background will be city, fought for the recently imple- Although he had not previously valuable assets at the FDA. Barry mented ban on smoking in Balti- worked as a manager, he has ef- Zuckerman, chair of pediatrics at more’s bars and restaurants, and fectively run an agency with 1000 Boston University School of Med- sought to help the city’s seniors employees and a $200 million icine and a longtime mentor, said and low-income residents obtain annual budget, Klag added. “He his former resident Sharfstein “can coverage for prescription drugs is a nuts-and-bolts guy. He gets solve problems better than any- under Medicare Part D or local under the hood and makes the one I know. He will figure out the

Bloomberg/Landov drug-assistance programs. system work.” strategies to be effective.”

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out clinical testing of safety and medicines to look for adverse ef- commissioner will most effective- efficacy, provided they are deemed fects and measure long-term ef- ly serve the American people. substantially equivalent to devices fectiveness, and the FDA has be- No potential conflict of interest relevant already on the market. Despite gun working with organizations to this article was reported. 1990 legislation ordering the agen- that maintain large databases of Dr. Okie is a national correspondent for the cy to begin requiring more exten- information on patients to es- Journal. sive clinical studies of class III tablish the Sentinel System, in 1. Harris G. Report criticizes F.D.A. on de- devices (those implanted in the which a drug’s safety profile can vice testing. New York Times. January 16, body) before approval, most are be efficiently evaluated by epide- 2009:A15. still approved with minimal test- miologists. The goal is to have 2. FDA Science Board. FDA science and mission at risk: report of the Subcommittee on 5 ing. An “improved” pacemaker 25 million records available for Science and Technology. Bethesda, MD: Food wire that was approved in this such studies by 2010, an FDA of- and Drug Administration, November 2007. manner recently caused deaths ficial said. 3. Green M, Jolin M, eds. Change for Ameri- ca: a progressive blueprint for the 44th presi- when it fractured after being im- Although commissioners of- dent. New York: Basic Books, 2009. planted in patients. ten take on the job because they 4. Drug safety: better data management and Regarding drugs, the FDA must are interested in a specific issue, more inspections are needed to strengthen FDA’s foreign drug inspection program. continue to focus on striking the fixing the FDA will require a lead- Washington, DC: Government Accountabili- right balance between safety and er who is passionate about the ty Office, September 2008. (Publication no. efficacy and on promptly sharing agency and its mission as a whole. GAO-08-970.) 5. Medical devices: FDA should take steps emerging safety concerns with By restoring science to its right- to ensure that high-risk device types are ap- doctors and the public. There is ful status, by forcefully advocat- proved through the most stringent premar- consensus on the need for com- ing for needed resources, and by ket review process. Washington, DC: Govern- ment Accountability Office, January 2009. panies to conduct more postmar- improving the FDA’s record as a (Publication no. GAO-09-190.) keting studies of newly approved guardian of public health, the new Copyright © 2009 Massachusetts Medical Society.

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