Ethics of surgical innovation to treat rare diseases☆

A gynecologist has referred you a 50-year-old woman with extensive intravenous leiomyomatosis. A tissue diagnosis of invasive low-grade malignancy is available, and the tumor extends into the renal and hepatic veins. You propose removing the tumor by hysterectomy, to be combined if necessary with an extensive venectomy. The patient has had multiple vascular procedures which have exhausted all her available autologous graft material. You will try to excise the tumor through a venotomy, but it is likely that reconstruction will require venous replacement with prosthetic material, for which you have chosen externally supported polytetrafluoroethylene. What is the ethical course of action?

Since ancient times, surgeons have individualized therapy to one degree or another without seeking supervision or prior approval by third parties. Past murmurings about excessive surgical autonomy, however, have culminated in recent calls for regulation of “significant” innovations.1, 2 Surgeons exercise autonomous judgment when they select, titrate, or discontinue medications, prophylactic antibiotics, and prep solutions; make transfusion decisions, incise, and anastomose; or choose a suture material and the way to tie it. These are judgments made in consideration of each patient's condition, clinical indications, and the surgeon's personal experience and preference for materials with which he has familiarity and confidence. When treatment proceeds without complication, such idiosyncrasies are well within the range of normal variation seen in every practice. Neither individual preferences nor autonomy are problematic in and of themselves when the surgeon is using materials and techniques that will afford his patient a highly predictable therapeutic result. The decision-making authority to implement innovations, understood as adjustments to existing norms, is granted to the surgeon by the culture and by the patient. This authority is based substantially upon the understanding that the surgeon has completed a course of accredited training, has accumulated some experience, and is well prepared to make such judgments in order to achieve a favorable treatment outcome. The patient's provision of informed consent for the operation described is typically supplemented by the standard phrase “and all other necessary procedures,” and confers upon the surgeon the wide discretionary latitude he needs to manage unforeseen complications or occult pathology revealed intraoperatively. To evaluate the boundaries of this latitude, we must distinguish between innovation and experimentation.

Defining our limits requires us to define our terms. What, then, do we mean by “surgical innovation”? The Oxford English Dictionary's etymology of “innovation” offers the Latin root “innovatus,” to renew or alter, implying revision or modification of something that is already established. If one accepts the limitations this definition places on the word “innovation,” most innovation is not only acceptable but also desirable. Alternatively, innovation is recognized as the introduction of something entirely new. From this point of view, the phrase “surgical innovation” suggests necessary and desirable features as well as some that may be unnecessary and undesirable. Every surgeon has a clear idea of personal boundaries, but it is safe to say that the limits of acceptable innovation are neither widely accepted nor closely observed by the profession at large.3

Tonelli and associates4 studied lung volume reduction surgery and concluded that the different nature of the informed consent can provide a test of whether a new treatment is experimental.The consent process in conventional treatment includes a discussion of what is known, but in experimental treatment the discussion must concentrate upon what is not known. When uncertainty of outcome enters the informed consent process, the concept of experimentation becomes a consideration. Because the present case involves a malignancy, experimental therapy is clearly indicated, but one should remember that, when not indicated, such therapy is “reckless experimentation.” In rarely done procedures, the surgeon must evaluate whether data developed to resolve the uncertainty is sufficient and adequately studied to predict outcome of the proposed therapy. The patient always should be told how many such procedures the surgeon has done, as well as the associated morbidity and mortality rates. It is not enough to cite the statistics of other surgeons and institutions with similar procedures. When engaging in planned experimentation, the surgeon is obligated to obtain permission from the patient or his surrogate, after providing transparent disclosure of the uncertainty of outcome when appropriate to the operative conditions. If circumstances do not permit prior consent, then the patient or surrogate must be informed completely of the experimental nature of the surgery and the uncertainty of outcome at the first reasonable opportunity. This practice is common and well-observed among surgeons. Because of the unpredictability of the procedure and its outcome, the adequacy of the informed consent process is essential. It must make clear the limits of what is known and the relatively high degree of uncertainty. One must disclose that the types and rate of complications are uncertain as well. These considerations eliminate Options B and C as inadequate to the purpose.

Tailoring surgical therapy to rare diseases for which there is no standard treatment may be seen as experimentation, but its intent is clinical rather than scientific. The unusual nature of the proposed procedure imposes additional obligations to ensure the patient's full prior understanding, but not the approval of a scientific review panel or an ethics advisory board, eliminating answers D and E. The now-venerable Belmont Report distinguishes between clinical practice and research on the basis of the clinician's intent.5 “Practice” refers to interventions that are designed solely to enhance the well-being of an individual patient and that have a reasonable expectation of success. Innovation which “departs in a significant way from standard or accepted practice” is experimental, but becomes research only when its scope extends beyond the individual patient by producing generalizable knowledge.

There is no intent to include this patient in a series for purposes of systematically developing a new body of knowledge or surgical technique for future application to others with similar conditions; the intent is solely to provide clinical care. All associated clinical decisions are based entirely upon this patient's clinical indications; clinical options will not be limited by conformity to a standard research protocol and there will be no effort to establish scientific controls to produce replicable results. Since surgeon/patient autonomy is the cornerstone of legitimacy in experimentation, the completeness of consent is the single most important ethical consideration,6 and Option A is the most appropriate response.

Some would propose that review of such therapies be mandatory, and we would agree if the procedure is used to treat diseases that are likely to be encountered repeatedly, but not for treatment of rare conditions as the present case. A surgeon, especially one newly-minted, might be wise to informally consult with the surgeon-in-chief for future political support, but since all surgeons should be competent technically and none would be likely to have experience with the case described, consultation would be expected to add little.

The Belmont Report suggests that radically new surgical procedures be made the objects of structured research soon after their introduction for purposes of scientific evaluation. The widespread occurrence of severe bile duct injuries following the unregulated combination of two established procedures, cholecystectomy and laparoscopy to become laparoscopic cholecystectomy, is an oft-cited example.1 Radically different surgical procedures applied without oversight when well-established effective methods are available are sharply criticized in the ethics literature.