March 11, 2003 — Editor's Note: Despite the proliferation of medical research, much of this new information is not affecting clinical practice. A panel of experts representing a diverse group of stakeholders in the nation's clinical research enterprise explores these issues in a Special Communication in the March 12 issue of The Journal of the American Medical Association .
The two main culprits, or "translational blocks," seem to be that basic science discoveries are not rapidly leading to clinical trials, and that findings of clinical studies are slow to influence medical practice and healthcare policy. Factors contributing to these translational blocks include high costs, slow results, lack of funding, regulatory burdens, fragmented infrastructure, incompatible databases, and not enough qualified investigators or willing subjects. The Clinical Research Roundtable (CRR), which first met in June 2000, is focusing on how best to meet four central challenges to clinical research: public participation, information systems, workforce training, and funding.
In an accompanying editorial, Roger N. Rosenberg, MD, from the University of Texas Southwestern Medical Center in Dallas, suggests that one solution might be to establish a Department of Biomedical Research analogous to the Department of Homeland Security. "A unified voice from the biomedical community must speak clearly and resolutely to emphasize that the CRR report amounts to a national crisis," he writes. "The American people need to know that the current system for bringing promising medical research to the bedside is operating at an obsolete level of efficiency, causing great delay, and consequently resulting in the loss of many lives."
To further define the problems and possible solutions, Medscape's Laurie Barclay interviewed lead author Nancy S. Sung, PhD, program officer of the Burroughs Wellcome Fund in Research Triangle Park, North Carolina.
Dr. Sung: Unlike basic biomedical research, each step in clinical research requires the direct involvement and consent of the public, working in partnership with clinical investigators and operating in compliance with government regulations. This bidirectional movement of innovations from the laboratory to clinical trials and from patients back to basic laboratories is increasingly encumbered by high costs, slow results, lack of funding, ever-increasing regulatory burdens, fragmented infrastructure, inefficient processes, incompatible databases, and a shortage of qualified investigators and willing study participants. This bottleneck is becoming increasingly evident as the promise of the genomic era is stalled by the burgeoning crisis in healthcare funding.
Dr. Sung: Clinical studies have provided solid evidence to support diagnostic and therapeutic approaches that, in many cases, are only sporadically applied to the patients who need them. Where strong evidence-based practice guidelines exist, they are frequently not followed by physicians and other practitioners. Comparative data on the effectiveness of old versus new technologies and therapies is often lacking. Comparative data on the effectiveness of population-based public health approaches to improving health are even more scarce. Consequently, significant holes exist in the body of evidence from which clinicians and consumers base health promotion and treatment decisions, and on which health plans and employers make coverage decisions.
Without a solid base of evidence from well-designed clinical studies, insurance benefits may limit coverage inadvertently by placing some new and potentially better, but very expensive, therapeutic interventions out of reach of ordinary consumers. Conversely, benefits may include coverage for therapies that are of questionable value or even have been proven ineffective. These problems will become more acute as the pace of medical and health sciences innovation quickens and as the need looms to find more effective approaches to preventing disease and promoting the health of the public.Medscape: What are the goals of the CRR, and what progress toward these goals has been made to date?
Dr. Sung: While most of the authors are members of the CRR, the thoughts expressed in this paper reflect the opinions of the authors and not of the roundtable as a whole. That said, the goal of the CRR is to create an enhanced environment for the conduct of a broad agenda of high-quality clinical research. This goal is achieved through voluntary consensus of the stakeholder members of the roundtable.
The leadership of the National Institutes of Health (NIH) has recognized many of the problems identified by the CRR concerning the future workforce, information systems, and public engagement. Elias Zerhouni, the NIH director, is generating plans to re-engineer the clinical research enterprise, echoing much of the work of the CRR. The CRR applauds this NIH initiative but also recognizes that NIH's mission does not reach all the needs of the clinical research enterprise. For example, employers and health insurers have commented that the output of the clinical research enterprise has not met their needs to support evidence-based medical policy and coverage decisions. The CRR is exploring mechanisms to address this and other issues present in the second translational block.Medscape: You cite various obstacles to clinical research: high costs, slow results, lack of funding, regulatory burdens, fragmented infrastructure, incompatible databases, and a shortage of qualified investigators and willing participants. What is the relative impact of each of these factors on slowing research, and how can we best correct these problems?
Dr. Sung: The clinical research enterprise is an interconnected system comprised of "stakeholders" all carrying out their own tasks, and there is currently no quantitative data on the isolated impact of each of these factors as they affect the different public and private players. Correcting them will require collaborative solutions across the health and research sectors. The paper provides specific recommendations for addressing each of these, in the context of four central challenges: public participation, information systems, workforce training, and funding.Medscape: While the importance of workforce training and funding seem intuitively clear, how will addressing public participation and information systems improve clinical research?
Dr. Sung: Given the pace of discovery in biomedical science, the number of planned clinical studies and participants needed for those studies is increasing. Furthermore, only a fraction of those who respond to trial recruitment efforts actually end up completing a trial. While the public remains highly supportive of our research enterprise, concerns about safety, in light of recent high-profile clinical trial tragedies and medical errors; concerns about the privacy of medical records, and concerns over financial conflicts of interest must be addressed if we are to expect this precious public trust to continue. The clinical research enterprise presently contains inefficiencies at almost every step. We lack data on the numbers of adverse events or the denominator of how many are actually enrolled in clinical studies. Without such information there is no way to know if presumed improvements or additional regulations actually result in a safer study. Most medical records are kept manually. Clinical research staff are often overtaxed. Replicated entry of data on charts, insurance claims forms, clinical trial forms, and adverse event forms is the rule. Greater application of standardized electronic record-keeping seems a logical means to increase efficiency. Standardization in other industries has facilitated vast savings through process improvement, and information technology has been an integral part of this transformation. This same revolution has yet to happen in healthcare — indeed, the entire healthcare industry continues to invest significantly less in information technology than any other information-intensive industry. Progress in developing information technology solutions is likely to improve not only system efficiency but also patient outcomes, for example, by reducing medical error rates, more rapid availability of critical information, etc.Medscape: How can we best balance timely introduction of new drugs and treatments with safety issues?
Dr. Sung: To quote coauthor Bill Crowley, "Efficiency is not the enemy of safety." The introduction of efficiencies, particularly at the level of duplicative IRB (institutional review board) review at multiple trial sites, is critical.
Dr. Sung: Researchers must work to build and sustain trust in ways that go beyond enactment of new regulations to protect safety and privacy. As the need for participants in clinical research studies grows, participants are likely to demand greater ownership over the entire process, from initiation of the study questions, to study design, to ethical review to analysis and implementation of results. They will want to see that the clinical research enterprise is genuinely responsive to their needs and concerns.Medscape: What should research funding priorities be in the government and private sectors? What is your justification for recommendation doubling of our annual budget for healthcare research?
Dr. Sung: The Institutes of the NIH are charged to develop funding priorities, which primarily address the first translational block. The CRR has worked with the purchasers and payors of healthcare to develop a prioritized list of research questions they need the clinical research enterprise to answer. Beyond this, the Institute of Medicine has developed specific research priorities, related to chronic disease, for the AHRQ (Agency for Health Care Research and Quality). Population-based or public health priorities are even less well articulated and developed through separate mechanisms from those I just mentioned.
The current fragmentation and underfunding of today's clinical research infrastructure clearly limits its capacity to handle the unprecedented opportunities that are increasingly presented by the ongoing basic research investment. Enhanced cooperation and optimization of this national clinical infrastructure has been identified by the Institute of Medicine's CRR as an emerging national priority. Improving the safety of and increasing the public's confidence about and participation in clinical studies, bringing to bear the full force of modern information technology, developing a pipeline of well-trained and highly motivated investigators, and providing a context of stable and ample funding for the enterprise represent common themes that must be addressed soon to enable the biomedical research machinery to operate at maximum efficiency. Only if these objectives are met can we fully achieve the promise of better health made possible by a century of advances in basic scientific research.
Dr. Sung: These problems cannot be solved by the government alone. The magnitude of the problem, however, begs for a solution at this level. One possible route is the creation of a nationalinstitute for clinical research, either as part of the NIH or as a stand-alone agency. Another approach is to augment the funding of our current agencies such as the NIH, VA (Veterans Affairs), and especially the CDC (Centers for Disease Control and Prevention) and AHRQ, whose portfolio is most attuned or congruent with the second translational block. In addition, a formal public-private partnership structure, in which all participants are represented, and to which all participants contribute, is sorely needed. For example, while the government can facilitate and mandate the development of appropriate informatics standards for clinical research, these standards cannot be developed without the active partnership of the pharmaceutical industry, academic health centers, and health systems. These issues are too big and too systemic to be solved by one entity.
JAMA. 2003;289:1278-1287, 1305-1306
Reviewed by Gary D. Vogin, MD
Medscape Medical News © 2003 Medscape
Cite this: Laurie Barclay. Clinical Practice Lags Behind Medical Research: A Newsmaker Interview With Nancy S. Sung, PhD - Medscape - Mar 11, 2003.