Alead article in the New England Journal of Medicine describes a retrospective cohort study comparing clinical outcomes in patients with patent ductus arteriosus (a common cardiopulmonary complication of prematurity) who had undergone standard surgical closure of the ductus with patients who had undergone transcatheter placement of a new device designed to occlude the ductus nonsurgically.(1) The authors state: "Placement of the occluder is currently considered investigational by the Food and Drug Administration." Nonetheless, in their methods section they describe the population of patients receiving occluders in the following way: "Although the choice of treatment reflected the physician's judgment, policies at the six occluder centers generally favored use of the device in eligible patients." And in the discussion section they observe: "New procedures are infrequently evaluated in randomized trials.... No randomized trial comparing the two strategies for closure of patent ductus arteriosus has been performed.... The rapid, almost universal adoption of the occluder device in some centers coincided with the continued exclusive use of surgery in comparable institutions." They concluded: "Despite the inherent promise of the new procedure, our results do not provide support for its widespread dissemination."
Later in the same issue, an editorial challenges those results.(2) The author first observes that the device is commercially available outside the United States, despite its investigational status here. Next he identifies some flaws in the study, concluding:
Finally, and most important, the study compared the results of the first 4 1/2 years of experience with catheter occlusion with the results of 50 years of experience with surgery.... With the cumulative effects of time, competition, and new technology, catheter occlusion of the ductus should become cheaper and more effective. Premature acceptance of the results of the comparison... of an established method with one in its infancy could stifle innovation and be disadvantageous to patients.
Together these articles constitute a classic example of the venerable debate about the status of new treatments: Are they experiment, or are they therapy? It is striking that neither article calls for the randomized trial that has never been done to compare these procedures, each considering such a trial unnecessary in light of the available data, even though the conclusions they draw from those data are in diametric opposition. It is even more striking that neither appears to wonder about the patients who are offered a treatment that reflects "the physician's judgment," even though the device has investigational status only, surgical ligation is effective, and catheter occlusion is "in its infancy." Reading these articles I wondered what these patients (or, rather, their parents, because virtually all such patients are infants and young children) had been told about the investigational status of the occluder, the relative lack of information about its efficacy and safety, and the availability of a proven standard therapy. Their physicians, I am certain, were acting for the benefit of their patients in recommending the occluder instead of surgery. But should they have seen themselves as engaged in research instead?
Experiment: A Meaning in Context
Historically, medical treatments have long been distinguished from "experiments." Experimentation bears connotations of heroism--the risktaking researcher who struggles altruistically, ultimately making the intuitive leap that saves patients' lives. But it also bears connotations of inhumanity, even monstrosity--of amoral or evil researchers and maimed and betrayed subjects.
In particular, the term experiment embodies societal ambivalence about what is new in medicine. We embrace innovation and recoil from it at once. New AIDS drugs, new cancer treatments, prenatal surgery, gene therapy, and a host of other examples from the nightly news have forcefully and repeatedly raised questions about when and how new technologies should be made available, who should have access to them, and who should pay for them. …