FOSTERING INNOVATION IN MEDICINE AND RESEARCH培养医学创新研究.doc

“Fostering Innovation in Medicine and Research”Eve E. Slater, M.D., F.A.C.C.Assistant Secretary of HealthDepartment of Health and Human Services2002 Charles C. Leighton, M.D., Memorial LectureFriday, October 18, 2002Leonard Davis Institute of Health EconomicsUniversity of Pennsylvania_It is a great pleasure to be here today among my many friends and former colleagues at Merck Research Laboratories and the Leonard Davis Institute of Health Economics of the University of Pennsylvania. While attending each and every prior Charles Leighton Memorial lecture, little did I ever imagine that today I would be appearing before you, representing the U.S. Department of Health and Human Services. It has been an exhilarating, if not somewhat daunting, time to join government, and of course a tremendous honor to be serving in this Administration. I have learned more this past year than I ever thought possible. Notwithstanding an occasional frustration of the transition from private to public sector, each day I am remarkably invigorated by Secretary Tommy Thompson and his dedicated team, who are committed to improving health for all Americans and to tackling the big problems that face us, including the need to improve health care at a time of cost escalation beyond available resources.Thus today, rather than focusing on drug costs, which I gather is the theme of your lecture series, I have elected to focus on innovation: how it can be fostered by government and how it can be used to improve health care and mitigate rising costs. Innovation has been a theme for many presentations by many distinguished speakers, including several by Merck CEO Raymond Gilmartin. I especially remember one that I helped to organize at the Royal Academy of Medicine in London in 1998 (Gilmartin, 1998). The topic is essential to our core activities, and it is all the more germane today. My remarks will be selective, but hopefully not myopic.In getting to know my new city, I recently visited the awe-inspiring Library of Congress, whose collection began in 1815 with the purchase of the 6,500 books belonging to President Thomas Jefferson. Many of those books remain on display there. Jefferson had organized his collection into three categories: Memory, by which he meant books on history; Reason, which included the writings of the philosophers; and Imagination, which to Jefferson referred to books about the fine arts. Let us take the lead from these categories to briefly highlight the memory of selected Federal incentives which fostered innovation, the reasoning upon which future strategies should be built, and, of course, conclude with an imaginary look at what may lie in store.By all objective measures, innovation in biomedical science over the past century has been unparalleled in history. Occasionally I wonder why we do not revel more in our successes. In the past 50 years, 5-year cancer survival rates have risen from 30 % to over 60 %. Cardiovascular mortality between 1950 and 1990 has decreased by about the same number, 60 %. HIV/AIDS has been transformed into a chronic disease in this country, owing in part to some of you in this room. Vaccines have eradicated many once-fatal diseases, including smallpox, which was eligible for total destruction by the World Health Association this past May in Geneva, were it not for the possible diabolic motives of a few players on the world stage. In 2002, my office, the Office of Public Health and Science, initiated a worldwide effort under the auspices of the CDC and WHO to inventory laboratory stocks of polio virus, in preparation for its potential destruction. Life expectancy for a 45-year-old has increased 9 years since 1950. On February 15, 2001, Nature published the initial sequence and analysis of the human genome. What crowning achievements, and we have only just begun.Almost as remarkable to me is the correlative observation that while the reductions in morbidity and mortality that derive from medical inventions and their increased use are of tremendous moral and social value, economists can show a financial return on these investments, by adding back the costs saved by improved health and longer life. In a paper by Dr. Mark McClellan, the FDA Commissioner nominee, who is both a physician and an economist, the authors analyzed cardiovascular mortality, in particular from heart attack. They concluded that much of the mortality risk reduction resulted from changes in the use of pharmaceuticals and intensive medical procedures. Furthermore, while greater use of the fruits of these innovations increased medical cost, the health improvements which derived added back value in increased employment, lesser subsequent hospital bills, etc., so that overall costs for people with heart attacks fell (Cutler, McClellan, and Newhouse, 1998). I am well aware that I am among many health economists today, and that conclusions regarding the costs and/or values of innovation are highly dependent upon the assumptions used. I do not wish to enter those debates today. Notwithstanding your point of view, my thesis is straightforward: new innovation is not only desirable, it is essential. I accept that investment in innovation adds value to society. We must direct this innovation toward translational research: to applicability and access and toward reduced cost.What do we now need to further support and provide continued innovation? Returning to my theme, what is the memory of Federal contribution to innovation, and what can we learn to ensure it in the future?One of the fundamental requisites for the public health successes that I outlined above has been Federal funding. Clearly, one can never deny the power of money. We owe much to the Federal commitment to fund biomedical research, championed through many Administrations and on Capitol Hill, and brought to fruition over the past 5 years by President Bushs completion of a doubling in NIH funding to $27 billion dollars in fiscal year 2003. As a reference, this funding in 1960 (around the baseline for my statistics) was $182 million. Clearly the industry has contributed mightily as well, with the output of the private sector in support of biomedical research thought to have surpassed that of the NIHs in 1990 (Testimony, N IH Oversight, 107th Congress, 2002). I need not remind this audience that the cost of developing a new pharmaceutical is now pegged at $802 million (Tufts Center for the Study of Drug Development, 2002).Funding for clinical research, a fundamental component of this unprecedented progress, has kept pace with the encouragement over time from the IOM, the AAMC, the AMA, and the NIH itself, whose Directors panel chaired by Dr. D. G. Nathan led to the Clinical Research Enhancement Act of 2000, which secured a balance of NIH funding for primary clinical research. Importantly, their definition of clinical research was broad, and included the related disciplines of behavioral medicine, epidemiology, outcomes and research (Nathan, 2002). A recent GAO report notes that approximately 32 % of NIH funds in 2001 were spent on clinical research (General Accounting Office, 2002). But public spending is not enough. It must be directed by legislative initiatives. Legislation has provided much impetus to innovation over time. The Bayh-Dole Act of 1980, together with technical amendments and clarifying legislation passed in the ensuing decade, removed barriers to the ownership of patents on inventions supported by Federal funds to non-profit and small businesses. As a consequence, yearly patents to universities rose from 250 to approximately 2000; adding about $40 billion to the U.S. economy and more that 260,000 jobs in 1999 (Cornell Research Foundation, 2001). Also passed in 1980, the Stevenson-Wydler Act and subsequent Federal Technology Transfer Act of 1986 have stimulated government-owned and operated research laboratories to proactively seek private-sector partnerships and technology transfer opportunities. The National Cooperative Research Act of 1984 went further to promote private-sector innovation by removing some fears of antitrust violations for those companies entering into pre-competitive research and development ventures. I do not include in this review the many legislative initiatives intended to protect intellectual property, for example The Hatch-Waxman Act, or the Orphan Drug Act of 1983. It is important to recognize, however, that an IOM Conference in 2001 (National Research Council, 2001) raised the specter that “the incentives written into these two laws may not now be economically relevant.”So where does our collective reason now take us? Or should we simply remain on automatic pilot? Clearly, one cornerstone of improving systems of care would be to reassess our reimbursement schemes, weighting more toward innovation and toward prevention. Of current health care spending, 90 % is directed toward treatment; 10 % to prevention. Whereas, were we capable of preventing three conditions: smoking, obesity, and diabetes, 1 million American deaths would be avoided each year and $287 billion could be spent elsewhere. This is one place we ultimately must go to curb our escalating health care budget. Innovation must look increasingly toward disease prevention and better translation of our innovation to make patients better, whomever they may be and wherever they may live. There is growing recognition of this need and one can only view the evolving political landscape to predict whether and when these initiatives may take shape.But there is major change possible without major legislative action. According to Senator/Dr. Bill Frist, in his editorial this past May in JAMA, “ todays challenges require a substantially improved ability to translate scientific knowledge and technological capability into daily medical practice.” He went on to state, “ an improved process is needed for establishing goals and research priorities based on scientific datamoving beyond input measures to develop new metrics to measure scientific advances and their causal relationship to health outcomes.” He recommended “an improved public dialogue on every level with clear communication between policy makers and stakeholders on the priorities and their justification.” Frist concluded (and here is the prescient comment), “These new paradigms will require a reexamination of the structure of the U.S. medical research institutions and government to ensure that they reflect and accommodate new multidisciplinary research and development processes” (Frist, 2002).Herein Senator Frist has redefined innovation for this decade and called for a new paradigm in biomedicine based upon priority setting for research and development that should derive from national dialogue. Priority setting by dialogue can begin as we speak. To Frists call to action, I would add my own personal belief that unless we begin this conceptualization now, we are vulnerable to stagnation: to flat-lining of pipelines to delaying the promise of genomic research, to making more inaccessible the fruits if innovation owing to inexorably rising costs. The gap between innovation and application will become a great divide. Research to improve applicability and access and to reduce costs must lead the list of priorities. We must, however, not lose sight of another very important aspect of governmental support, and that is the development and support of infrastructure. Dr. Charles Leighton, for whom this lectureship is named, was visionary in this regard. He foresaw the need for industry to develop an infrastructure of quality to successfully compete. His creation of the department of Quality Assurance to check and balance quality control set Merck apart from others in the industry for many years and created an atmosphere of quality that permeated the institution. Clearly, some may view government regulations as burdensome and anti-innovation. Dr. Leighton grasped the equipoise, if you will, of checks and balances as an essential ingredient of success.So too, the Federal government plays a role in promoting quality by infrastructure development. This year, the President has urged Congress to pass legislation to protect genetic information. HHS has begun several initiatives, such as regulatory reform, with a primary focus on simplifying the paperwork. As I stated in my editorial in Mays New England Journal of Medicine, our research engine has grown out of proportion to the ability of institutions to support the IRB, the critical element to assure human subject protection during clinical trials (Slater, 2002). The rebuilding has begun, with support from the Offices of Human Research Protections and Research Integrity within my office. The federal rules will be consolidated, and we are drafting guidance on Conflict of Interest and a Federal guidebook to IRBs.What about medical errors? Has the knowledge database grown so rapidly that many cannot keep pace? We have all read the IOM reports “To Err is Human” and “Crossing the Quality Chasm,” with a new report promised this month (IOM, 2000 and 2001). We know the data: between approximately 45,000 and 100,00 medical errors occur yearly, costing an estimated $17 to $29 billion dollars (enough to fund the NIH). The cost to hospitals from medication errors and drug adverse events totals $2 billion per year. How much suffering could be alleviated? How better could our money be spent? This year, Secretary Thompson requested FDA to publish a proposed rule on barcoding drugs products and biologics; a public meeting to solicit comment was held this summer. Other activities are in progress.Last month, Secretary Thompson testified vigorously to the House Subcommittee on Health of the Ways and Means Committee in support of legislation aimed at tort reform and other measures to improve health care safety. I quote, “ the Administration supports your efforts to pass and enact legislation to remove liability barriers to improving quality and safety of health care” (Testimony, Reducing Medical Errors, 107th Congress, 2002). What about drug development times? The FDA Commissioner-nominee testified during his confirmation hearing that he didnt “think there needs to be a conflict between stressing safety concerns and handling them appropriately, and approving drugs quickly” (Kaufman, 2002). We read that a $100 million reduction in total capitalized cost per approved drug could be achieved by either a 19 % decrease in all phase lengths or an increase in the clinical success rate from 21.5 % to about 25.5 %; cutting one year from phase III clinical studies would save an average of $71.4 million from the total cost of a new drug; a 33% reduction in development and regulatory review time (four years) would decrease average capitalized cost per approved new drug $167 million (21%) (Tufts Center for the Study of Drug Development, 2002). The reauthorization of PDUFA in 2002 took a step in the right direction. But why have I progressed from research funding, to translational medicine and the needs for prioritization of biomedical research, to regulatory reform in the broadest sense of the term? I have, because in addition to the financial support of innovation, the development of priorities and the initiation of dialogue, one of the most critical functions of Federal government is to support the development of infrastructure to enable creativity and innovation to proceed, while at the same time dedicating ourselves to the preservation and enhancement of quality.There was a reason that I structured this lecture to flow in this direction. It is because of the fact that of all the distinguished prior speakers at the lectureship, I am the only speaker who was trained by and worked with Dr. Leighton. Translation and quality were his bylines. He brought them to Merck and would have been very pleased to participate in a national dialogue on quality were he with us today.In another of my recent Washington meanderings, I visited that Egyptian exhibit at the National Gallery. One of the most treasured belongings of a buried nobleman, found in his tomb amongst the gold and jewels, was as triangle balance. It was a beautiful triangle with a plumb line found in the tomb of Sennedjem (c1300-1270 B.C.). Apparently, Sennedjems life was led by the principle or imagination that by keeping life straight one was doing right: indeed one was holding back hidden chaos. That is most definitely what Charlie would have asked of the scientists and policy makers of today: to foster a dialogue of quality that will allow us to prioritize, to translate, and to innovate.Thank you very much.ReferencesGilmartin, Raymond V. (1998) The Impact of Economic and Political Factors on Pharmaceutical Innovation. CMR Annual Lecture, 13. Royal College of Physicians, London.Cutler, D., McClellam, M., & Newhouse, J. (1998) The costs and benefits of inten