We believe that support for academic clinical research has greatly declined in recent decades. Here we discuss our views on why this has happened. We define clinical or patient-oriented research as limited to the study of human beings or populations of individuals, and argue that its eclipse in favor of basic and "translational" research is the result of inappropriate conceptual paradigms or "models" for medical advances. We believe that medical history shows that the "bench-to-bedside" model is inadequate to explain most recent progress and that clinical advances themselves often lead to new basic research. Discussion of alternate conceptual frameworks for biomedical research should help lead to changes in funding and organizational structures that might finally revitalize clinical research
Swazey, Judith P.
Fox, Renée C. (Renée Claire), 1928-
Clinical medicine -- Research -- United States -- History -- 20th century.
Medical research personnel -- United States -- History -- 20th century.
Physician and patient -- United States -- History -- 20th century.
The period from the end of World War II to the early 1960s has been characterized as the "golden years" of patient-oriented clinical research in the United States, a period catalyzed and fostered by advances in biology and medicine, changes in the organization and financing of research units, and strong moral and political convictions growing out of the war about the importance and possibilities of the scientific enterprise. This account of some of the salient themes, phenomena, and issues in clinical research during that era draws primarily on the proceedings of an oral history conference whose core participants were a number of emeritus physician-investigators who had played major roles in shaping patient-oriented research. The topics that they and the other conferees discussed included the factors that had led the emeritus physician-investigators into clinical research; the organizational attributes of the units where they had trained and worked, focusing particularly on Boston's Peter Bent Brigham Hospital; the vital role played by private and federal funding for research and training;
and some of the changes in the nature of clinical research, research training, and their relationships to the care of the sick in the decades since the golden years.
Neurology -- Research -- United States -- History -- 20th century.
Boston City Hospital. Neurological Unit -- History -- 20th century.
Harvard University's Neurological Unit at Boston City Hospital (BCH) became the premier center for neurological training in the United States during the middle part of the 20th century. During part of this period (1939-1967), it was directed by Derek Denny-Brown, who had been recruited from England by Harvard president James Conant. The training program that Denny-Brown initiated at BCH emphasized neurology as a medical specialty, independent of psychiatry and neurosurgery. This program, which reflected Denny-Brown's British training, was remarkably effective and served as a model for rest of the country.
Human experimentation in medicine -- Moral and ethical aspects -- United States -- History.
Pediatrics -- Research -- Moral and ethical aspects -- United States -- History.
Pediatrics -- Law and legislation -- United States -- History.
This paper examines the changes in policies regarding children in research between 1966 and 2003. The changes reflect a shift in focus from protection to access. The need for protection was brought to light in 1966, with the publication of Henry Beecher's "Ethics and Clinical Research," which described 22 research projects that he considered unethical. Four of these involved child subjects. Within a few years, Paul Ramsey and Richard McCormick debated the ethical acceptability of enrolling children in any non-therapeutic research. The first U.S. policies to address the protection of human subjects were written in the 1970s and 1980s, and additional protections (Subpart D) were provided to child subjects, who were considered particularly vulnerable. In the 1990s, however, several new policies were implemented by the National Institutes of Health, the Food and Drug Administration, and Congress, in which the focus had shifted from protecting children from research risks to ensuring access. The article describes the new policies, examines the motivations for the change, and describes some of the effects of these policies. It concludes by suggesting that greater attention must be paid to ensure that increased access is not achieved by undermining the additional protections to children provided by Subpart D.
Cancer -- Treatment -- United States -- History -- 20th century.
Cancer -- Patients -- Care -- United States -- History -- 20th century.
In April 1964, seven physicians met to discuss the formation of a new medical society for clinicians interested in the management of patients with cancer. Chemical warfare research during World War II had led to the advent of chemotherapeutic agents, a new, systemic approach toward cancer treatment. While skeptics questioned the benefits of chemotherapy, some internists viewed these drugs as promising new tools. Founders of the American Society of Clinical Oncology built their organization upon the importance, despite potential dangers, of utilizing chemotherapy as an essential component of cancer treatment, and positioned themselves as best qualified to manage the care of patients with cancer. The establishment of a new professional organization helped to anchor medical oncology as a distinct field during a time of increasing medical specialization in the United States. This essay examines the Society's early history within a broader context of the development of new chemical agents and cooperative groups, the formation of a new subspecialty, and increasing federal involvement in health care policy and funding, and describes the struggle of medical oncologists to solidify their authority over clinical cancer research and patient care.
Sickle cell anemia -- Treatment -- Technological innovations -- United States -- History -- 20th century.
The promise of molecular medicine is the prevention and treatment of illness. Understanding the mechanism of the disease should allow one to "fix" it. For sickle cell anemia, however, knowledge of the biochemical basis of the disease was only partly responsible for finding a means of treating the disease—of equal value were hypotheses and conclusions generated from clinical observations. This article describes the research path that led to the first effective treatment for sickle cell anemia, hydroxy-urea. Rather than exemplifying the "bench-to-bedside" model commonly used to describe the process of therapeutic innovation, this history of this research reveals that the critical advances for the development of treatment came not from basic research, but instead from clinical and patient-oriented research. Given that the linear approach is the prevailing paradigm of therapeutic innovation, this history is important because it indicates the inadequacy of this approach for a relatively straightforward single-gene mutation disease such as sickle cell anemia and suggests the need for multiple models of innovation for more complex diseases. Thus, this article questions the expectations of molecular medicine and the dominance of a linear model of therapeutic innovation, which often excludes or subordinates other models of developing treatments.
Non-insulin-dependent diabetes -- Chemotherapy -- United States -- History.
Hypoglycemic sulphonylureas -- United States -- History.
The University Group Diabetes Program (UGDP), launched in 1960, was an early placebo-controlled, multi-center clinical trial devised to determine which, if any, of the treatments for type 2 diabetes was efficacious. Because of an excess of cardiac deaths in patients treated with tolbutamide, a sulfonylurea drug, investigators terminated this limb of the study. This decision was met with strong resistance from the parent drug company and many in the medical community. Subsequent clinical studies both supported and conflicted with the UDGP findings, so that the controversy has persisted. A rationale for sulfonylurea-induced cardiotoxicity emerged with the observation that these drugs block ischemic preconditioning, a protective maneuver that reduces myocardial damage after temporary blockage of coronary blood flow; this action of sulfonylureas provided laboratory support for the UGDP findings. The development of newer sulfonylurea drugs that do not block ischemic preconditioning has rendered the UGDP controversy moot and has preserved a place for sulfonylureas in the treatment of type 2 diabetes.
Silverberg, Donald S., 1937-
Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure. Our joint renal-cardiac heart failure team found that anemia was indeed very common in congestive heart failure and was associated with severe, medication-resistant cardiac failure. Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized. Subsequent investigations by others have confirmed many of our observations. We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure may prove vital in preventing progression of both the heart failure and the associated renal disease.
There is a widespread view that clinical research is failing to advance appropriately, particularly in comparison with other aspects of biomedical science. I argue that this is due in part to an inadequate understanding of how medical advance occurs. The common usage of such terms as basic or fundamental, or the uncritical use of the term model is unhelpful—unhelpful, in that such terms tend to presuppose a certain model of clinical advance that is unusual, and furthermore, because they tend to exaggerate the importance of research in subjects such as biochemistry and genetics at the expense of other areas. I suggest that much medical research is best viewed as a form of engineering rather than science, and that the knowledge base and research funding for the amelioration of disease needs to be much more broadly based than at present.