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“Bench‐to‐bedside”—The Wrong Paradigm for Patient‐oriented Investigation

Stacpoole, Peter W. PhD, MD

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Dr. Stacpoole is professor of medicine, biochemistry, and molecular biology, and director, the General Clinical Research Center, University of Florida College of Medicine, Gainesville, Florida.

The author's work on this Commentary was supported by General Clinical Research Center grant RR00082 from the National Institutes of Health. He acknowledges the help of Waldo R. Fisher, MD, PhD, professor emeritus, Department of Medicine and Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, in its preparation.

“Bench-to-bedside” evokes a fundamentally misleading and harmful paradigm for describing patient-oriented investigation and those who conduct it. The phrase has become so firmly inculcated in the lexicon of academic medicine, however, that it is used unthinkingly to depict patient-oriented investigation as a process of scientific pursuit that is at best simplistic and at worst intellectually derivative. Implicit in the “bench-to-bedside” notion is the assumption of a linear and unidirectional process of biomedical experimentation, by which so-called “translational” (i.e., patient-oriented) research is necessarily preceded by and dependent on the creativity and hypothesistesting percolating up from laboratories conducting basic research.

Frequently, biomedical investigation simply does not work that way. It is the wonder and curiosity of an astute observer about the clinical phenomenology of human disease that ignites the creative spark and inspires both clinically and nonclinically trained experimenters to undertake relevant hypothesis testing. The process is highly iterative and palindromic. For example, an observation at the “bedside” may generate an attempt to explain a phenomenon, either by patient-oriented or by laboratory- (“bench-”) oriented hypothesis testing that is specific to the initial observation. The research quest may oscillate within and between the laboratory and clinical arenas, depending upon the nature of the postulates and the appropriateness of the venues in which to test them. In addition, the ideas spawned within the initial, narrowly focused, experimental framework may generate concepts or findings applicable to the elucidation of phenomena in other scientific areas. By such processes fundamentally new patient-oriented and laboratory-oriented research dynamics evolve.

Innovation in the causes, prevention, and treatment of human disease requires synergy between laboratory and clinical investigation. Hypothesis testing is integral to all stages of biomedical research, but the manner in which it is conducted in human subjects often poses challenges apart from those that do not require human experimentation.1,2 By virtue of their training, physician—scientists are uniquely positioned to recognize the inherent interdependence of basic and applied biomedical investigation and to exploit elements of each in developing their own academic careers. Moreover, physician—scientists are perhaps better able than most clinicians to appreciate that excellence in both patient research and patient care involves a continuous intellectual process, whereby puzzled observations are resolved by the formulation and testing of hypotheses.

Good hypotheses share two criteria: they are testable, and their testing gives rise to new ideas that can, in turn, be scrutinized experimentally. Their origin and the testing, however, are multidimensional. It is important to reject the “bench-to-bedside” concept of biomedical research for several reasons. To do so (1) endorses the equality and interdependence of patient-oriented and non—patient-oriented investigators and the science they pursue; (2) demands a level playing field for the peer review of creative, hypothesis-driven applications independent of the experimental settings in which they are performed3; (3) charges academic medical centers to incorporate support for patient-oriented research and training into their strategic planning; (4) stimulates medical students, housestaff, and fellows to train as clinical investigators; and (5) perhaps most important, encourages those future physician—scientists to view a career in patient-oriented investigation to be as rich in discovery and contributions as are those of any science.

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References

1. Goldstein JL, Brown MS. The clinical investigator: bewitched, bothered and bewildered—but still beloved. J Clin Invest. 1997;99:2803–12.

2. Rosenberg LE. The physician—scientist: an essential—and fragile—link in the medical research chain. J Clin Invest. 1999;103:1621–6.

3. Williams GH, Wara DW, Carbone P. Funding for patient-oriented research: critical strain on a fundamental linchpin. JAMA. 1997;278:227–31.

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© 2001 Association of American Medical Colleges

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