SYMPOSIUM AND MEETING REPORTS

The State of Clinical in America

Alan L. Buchman, MD, MSPH

Key Words: crisis in , American Federation for ated for academic . This model does not fit a , public policy, Bbusiness[ that is not subject to normal supply and demands. This creates a situation in which investigators have insufficient time to create hypotheses from clinical observations because they are forced to generate increasing levels of clinical revenue for their institution. Thus, is no longer hile Americans are experiencing an economic crisis of a 2-way street. It becomes a 1-way street centered around the W unprecedented proportion, we are also experiencing an laboratory. The business aspect of investigation also comes unparalleled crisis in clinical research. Somehow, the current into playVit is not so much the results that are so important, administration has not addressed the clinical-research crisis in but the financial rewards and the associated indirect costs its health care agenda. The first step to solve the crises in clin- collected along the way. ical research is to recognize that a problem exists and to iden- Programs to teach clinical investigators how to develop tify its cause. We are here today because we recognize that the studies, analyze results, and report those results are underfunded problem exists. and insufficient. Programs such as the Clinical and Transitional Awards have tried recently to improve research educa- WHAT HAS CAUSED THIS CRISIS tion, but these programs are still far from adequate. In addition, IN CLINICAL RESEARCH? American clinical research is moving offshore to China and India. We are endangering our future health care by not investing With that comes loss of American jobs and precious research properly in clinical research. Because of financial issues, re- funds. America needs to improve its research infrastructure and searchers are unable to continue in the field and make a living; our regulatory process to prevent this. Many of our regulations programs do not have appropriate funds to educate future are reactionary and based on righting past wrongs. In addition, American investigators. The research process is complicated by the public sector provides few funds for clinical research. Some minimal information about potential participants and lack of potential funders think that pharmaceutical companies should national databases and extensive regulations for researchers fund clinical research. If they uncover the pathogenesis of dis- and is paralyzed by a lack of communication and collaboration ease and determine the outcome of , we can apply their between various funding agencies and organizations (Table 1). findings and improve health care. However, the pharmaceutical These issues, which result from poor investments in clinical companies should not be expected to discover the pathogenesis research, result in fewer American researchers, fewer discover- of disease, appropriate diagnostics, and therapeutics. Their re- ies, and decreased health benefits for Americans (Table 2). sponsibility is to their shareholders and employees, and their re- Because of decreased funding, as well as a change in sponsibilities are to discover profitable new and to develop prioritiesVincluding a loss of respect for the clinical investigatorV profitable new devices and diagnostic tests. American institutions are losing clinical investigators. Re- Unlike European countries, the United States does not fund searchers are losing their jobs and are unable to find new jobs, or maintain disease databases. Our paternalistic instinct tells us so they are leaving clinical investigation and moving to more that documenting individuals’ health issues is an invasion of stable jobs. Professionals are not as interested in patient- privacy; yet, surveys show that the very patients who would be oriented clinical research, and in academic , leaders in those databases are willing to list their names and contact are forcing clinical investigators to choose between research information to participate in studies that may benefit them. and patient care. Those in academic medicine are not as in- Unfortunately, clinical researchers are experiencing increasing terested in being involved in patient-oriented clinical research difficulties when they seek patients for clinical research: for as they once were, and we are now witnessing a separation of clinical trials by the as well as research those who research from those who care for patients. As a in academic institutions and Veterans facilities. result, the concept of translational researchVtaking discoveries Communication in clinical researchVbetween government, from the laboratory bench and applying them to patient care, academia, and industryVis often haphazard and dysfunctional, or taking a clinical observation back to the laboratory for which decreases the likelihood of successful investigation and investigationVis becoming a distant reality. Also, because the also increases the cost of research. In this communication system revenue stream has changed, a business model has been cre- (Fig. 1), we do not find the insurance industry, which ultimately benefits from the results of clinical research. Insurance companies reap the rewards but do not invest in clinical research. Although different government agencies are funding clinical research, the communication between participants in clinical research, even From the American Federation for Medical Research and Medicine and within, or between government agencies, may be lacking. For Surgery and Division of Gastroenterology, Feinberg School of Medicine at Northwestern University, Chicago, IL. example, the Surgeon General’s Office, the National Institutes Received June 22, 2010. of Health (NIH), and the US Department of Agriculture are all Accepted for publication June 23, 2010. funding clinical research on pediatric obesity; however, no system Reprints: Alan L. Buchman, MD, MSPH, Division of Gastroenterology, exists to enable these 3 agencies to communicate to resolve gaps Feinberg School of Medicine at Northwestern University, 676 N Saint Clair St, Suite 1400, Chicago, IL 60611-5975. E-mail: a-buchman@ or overlaps in funding for this important clinical research. Prob- northwestern.edu. lems also exist when industry and government try to commu- Copyright * 2010 by The American Federation for Medical Research nicate and collaborate. For example, a pharmaceutical company

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TABLE 1.

FIGURE 1. The relationship between the current ‘‘players’’ in clinical research: academia, government, and industry. This often resembles the Bermuda Triangle. Where are the insurance companies?

ceutical as a source of revenue. As a result, clinical trials, for example, that are performed in academia are simply studies to get a approved and less focused on learning about disease might submit a plan for a new to the Food and pathophysiology or outcome. Drug Administration (FDA); the company will have already de- We are already witnessing a decrease in medical break- veloped a . If the FDA has questions about the trial, throughs by American investigators. This decrease leads to fewer the company must regroup and spend millions of dollars to cor- Americans who are attending and presenting data and scientific rect an issue because the government was not involved in the discoveries at leading scientific meetings. American scientific initial process. Another issue is that the FDA has given itself journals are also reporting that a majority of submissions are only the power to regulate new drug or device submissions, but from foreign rather than American investigators. Because we not to propose new products ripe for development. That is the are making fewer discoveries in America, we are making fewer Bstick[ without the Bcarrot[ approach. One wonders whether advances for American health and thus mortgaging our future this line of thinking represents Btradition[ or Bintuition.[ The health care. These fewer advancements lead to more - same communication issues occur between academia and gov- izations, more sick leave, lower production, and more job losses ernment and between academia and industry. The insurance in an economy that’s already stymied. These issues lead to infe- V industry has somehow escaped inclusion in this communication rior life expectancy which helps certain sectors of the econ- as well. omy but not the ones we would prefer to stimulate and leads to V Through the media, we witness conflicts of interest between decreased quality of life. Clinical research is shifting overseas the academic research enterprise, which has become a business specifically, to China and India, who have had the forethought in its own right, and the pharmaceutical industry. What was once to develop a research infrastructure necessary for cheaper and a cooperative relationship has disintegrated to a relationship in better research than what we have in the United States. However, which the pharmaceutical companies consider academia as a although some of their results may apply to Americans, other source of ideas to license, and academia looks to the pharma- research findings may not. HOW CAN WE SOLVE THIS CRISIS TABLE 2. IN CLINICAL RESEARCH? To solve this problemVthis crisis in clinical researchVwe must act. Several important steps necessary to reverse these trends are outlined in Table 3. We need to establish partnerships between the insurance industry, academia, government, and in- dustry. We must give clinical research a higher priority and make better use of our research funds. We also need to realize that the concept behind translational research is not just from bench to bedside, but also making astute clinical observations and taking those to the bench to investigate those observations. We need to simplify the process for identifying, informing, and enrolling potential study participants and provide sufficient time and resources for clinical investigators to make these astute obser- vations that have been the basis for many discoveries that we benefit from today. We must understand that clinical research is not just a purview of the pharmaceutical industry, but that we all benefit from clinical research, and therefore, all stakeholders need to work together. We need to improve cooperation between aca- demia and industry, between government and industry, and within the government itself (Fig. 1). We need to streamline our regulationsVthe consent procedures and institutional review boardsVso individuals participating in clinical research and

2 * 2010 The American Federation for Medical Research State of Clinical Research in America

tionships need to be cultivated in an appropriate and beneficial TABLE 3. way. We need public funding of voluntary disease-specific da- tabases with appropriate privacy safeguards so investigators can more easily recruit patients for studies and inform patients about studies. The government registry of most clinical trials (www.clinical trials.gov) was only a start. Currently, if a clinical study is not a clinical trial, this Web site does not list the study; therefore, investigators struggle to find patients for studies, even if they are simply studying the natural history of disease. We must enhance communication and collaboration be- tween the various government funding agencies and reevaluate the peer-review process. That process is unique and one that has served us well, but today clinicians must see more and more patients in academic institutions, where they are penalized for unfunded investigationVoften necessary for the initial testing of a hypothesis before a request for funding can be initiated, writ- ing papers, serving on journal editorial boards where observa- tions and discoveries are evaluated and critiqued, traveling away from the institution to meet with colleagues at other institutions or to publically disseminate the results of their discoveries or educate others in clinical research, to reviewing NIH grants, and even taking vacation time. As a result, basic are re- viewing clinical proposals, which they may not understand. We need to have cliniciansVnot basic scientistsVreviewing clinical proposals for funding.

HOW DOES THE AMERICAN FEDERATION FOR MEDICAL RESEARCH FIT INTO THESE RECOMMENDATIONS? The American Federation for Medical Research (AFMR) was established in 1940 by Dr. Henry Christian, who originally envisioned a forum where junior investigators could present their clinical research. The AFMR then evolved into a mul- tidisciplinary organization that is uniquely suited to address issues in clinical research because our membership includes their privacy are protected, but studies do not require years to several Nobel laureates, as well as members from every disci- complete. Finally, we must improve training and offer greater pline in medicine, in all 50 states, in all academic institutions incentives to attract clinicians, to properly train them, and to and many Veteran’s and private research foundations, retain them in an appropriate environment that fosters clinical and, in fact, across the globe. research. The mission of the AFMR is to promote the understanding We need an interagency task force to identify who is of recent advances in biomedical science for the prevention, funding clinical investigation, where the funding is occurring, diagnosis, and treatment of disease. We do not gather only as a and how much money is being spent. We cannot answer these scientific forum, but to create an environment and provide a questions currently. For example, we know that the Clinical and forum for the training of new investigators. The AFMR pub- Transitional Science Awards program spends approximately lishes a journal: the Journal of Investigative Medicine. The $370 million; the NIH budget is approximately $28 billion AFMR members are also involved in public policy. Members (and an additional $10 billion for 2009); however, we do not initially became involved in the creation and development of know how much of these funds are being spent in patient-based public policy when Hubert Humphrey was a senator, and since clinical research. We also do not know how much the pharma- then, the AFMR has advised various aspects of government on ceutical industry or private foundations are spending on clinical elements of clinical and medical research. One of the primary investigation. This task force will require congressional hear- goals of the AFMR is to foster education and development of ings: to find out where our money is going, what we are getting medical investigators. In fact, the organization’s name changed for these funds, where there are funding overlaps, and what is in 1995 from the American Federation of Clinical Research being underfunded or missed completely. Without this infor- to the AFMR so that our title fully encompassed the idea of mation, the health of the American people is at stake. translational medicine. Not only does the organization recognize We need to change the culture that currently exists and the need to educate future investigators, but also, and more continues to erode the relationship between academia, govern- importantly, we need to educate the public and government ment, and industry, while eliminating conflicts of interests. officials on the needs and on the crisis that we are experiencing Having a relationship is not a source of conflict, but those rela- in clinical research.

* 2010 The American Federation for Medical Research 3