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APPENDIX GASTRIC FREEZINGâA STUDY OF Â£) DIFFUSION OF A MEDICAL INNOVATION Harvey V. Fineberg INTRODUCTION Duodenal ulcer disease is a chronic condition that afflicts l in l0 Americans at some time during their lives.1 The disease is more common in men, who often first become symptomatic between the ages of 20 and 50 years, the most productive period of their lives. Peptic ulcer causes l percent of all disability due to chronic conditions in the United States. While it is not a leading cause of death, as many as l0,000 lives are believed lost annually as a result of this disease. Pathologically, duodenal ulcers are irregular, generally round, erosions in the first part of the small bowel. A number of causal factors have been proposed to explain the development of ulcers, including genetic predisposition, personality, endocrine abnormalities, and excessive gastric acid secretion.4 One prin- ciple in which all authorities concur is that ulcers never develop in the absence of acid, and reduction of stomach acid is a basic goal of therapy. While some patients with ulcer symptoms do have measurably excessive stomach acid, many have gastric acidity within the normal range. Clinically, duodenal ulcers produce abdominal pain, which is relieved by the ingestion of food or antacid. The natural history of the disease is characterized by remissions and exac- erbations.1,4 Typically, symptoms last for days, weeks, or months, remit for varying periods of time, and then recur without apparent cause. Most symptomatic episodes subside with conser- vative treatment, usually consisting of antacids, dietary regimens, and other medication. A minority of patients develop complica- tions, the most serious of which are gastrointestinal bleeding, l73
l74 bowel obstruction, and perforation of the ulcer into the abdom- inal cavity. Ten to 20 percent of patients develop intractable pain or serious complications that require hospitalization and may lead to surgery.4 Ulcers account for l.25 percent of all patient admissions to short-stay hospitals in the United States and for l.5 percent of all bed days in those hospitals.7 A variety of surgical interventions is employed in the treatment of complicated ulcer disease. The preferred surgical procedure is controversial, but each operation carries some risk of mortality and may be followed by uncomfortable sequelae.8'9 Given the operative risk and postoperative morbidity, surgery has rightly been regarded as a treatment of last resort. Gastric freezing was developed as an alternative to surgical treatment for patients with intractable pain from duodenal ulcers. First introduced clinically in l962, the treatment disseminated rapidly and was employed in thousands of patients over the next few years. Most physicians became disenchanted with the procedure, and its use in the United States all but disappeared by the latter part of the decade. This paper describes and analyzes the diffusion of gastric freezing in medical practice, the process by which it was devel- oped, disseminated, and later abandoned. Special attention will be given to the evaluation of this technique and to the relation between its evaluation and diffusion. Finally, policy lessons of this study will be described. DEVELOPMENT. OF GASTRIC FREEZING* Dr. Owen H. Wangensteen of the University of Minnesota Medical School became interested in the mid-l950ls in the use of gastric cooling to treat gastrointestinal bleeding. Then Professor of Surgery, Wagensteen was highly regarded as an imaginative and expert surgeon, and a gifted teacher. In the l950*s, one stan- dard treatment for patients with acute gastrointestinal bleeding was to lavage the stomach with iced saline passed through a naso- gastric tube.10 Wangensteen went further and in l958 proposed use of refrigerated alcohol circulated through a rubber stomach balloon as a means of stanching blood flow and in some cases averting the need for surgery.11 Dr. Wangensteen also became fascinated with the idea of using gastric cooling to reduce the secretory activity of stomach cells, which produce gastric acid. *Some material in this and the following section was obtained from personal interviews in l973 with Dr. Owen Wagensteen, Dr. Richard Goodale, and representatives of the Swenko manufac- turing company.
l75 He and his colleagues conducted many experiments in dogs, frogs, and other animals and were impressed by the reduction in stomach acid output following gastric cooling. In l959, Wangensteen published an article speculating on the potential of gastric cool- ing to treat peptic ulcer disease.12 Wangensteen and his colleagues then set out to determine the temperature and time limits for safely cooling the stomach of animals, and to measure more completely the effect of cooling on gastric acidity. In conducting this research, Wangensteen needed an efficient and reliable cooling device, and he turned to a small refrigera- tion company in Minneaspolis called Swenko. Engineers from Swenko collaborated closely with Wangensteen and his laboratory staff. At one time in l960, Wangensteen specified substantial improvements in cooling capacity and machine characteristics, which the Swenko people were able to supply in only 28 days. Under Wangensteen's prodding, Swenko developed and improved a refrigeration device that would rapidly cool alcohol to below 0Â°C and hold the temperature within narrow limits as the fluid circulated through the machine and entered and returned from the stomach via a double-barreled nasogastric tube. Wangensteen was convinced the reduction in gastric activity he had observed in animals after gastric cooling could occur in humans as well. To his surprise, he found he could safely treat the stomach of dogs with alcohol at -l5Â°C or lower without causing apparent harm. After trials in numerous animals, Wagensteen was prepared to try this gastric freezing method in ulcer patients with persistent pain in order to promote healing and obviate the need for surgery. A middle-aged lawyer with duodenal ulcer became, in October l96l, the first person treated with gastric freezing. The awake patient was placed in a semirecumbent position. After local anes- thesia of the pharynx, a specially folded rubber balloon was passed to his stomach and alcohol at a temperature of -l5Â°C was circulated through the balloon. The first human trial lasted about l5 minutes, but the usual duration of treatment in subse- quent patients was three or four times as long. Afterwards, the refrigeration unit was turned off and the system allowed to warm up, and then the alcohol, balloon, and tubing were withdrawn. The first patient happily reported that his symptoms had completely abated, and he was able to eat a regular meal l hour after the procedure. Wangensteen found the same remarkable results in the next two dozen patients treated, and he presented these dramatic findings at a meeting of the American Surgical Association in Washington, D.C., in May l962.13 Wangensteen conceived of gastric freezing as a means of achieving "physiological gastrectomy," eliminating stomach acid without surgical removal of the stomach, and he so
l76 titled his paper published May l2, l962, in the Journal of the American Medical Association.^1> In this paper, Wangensteen and his coauthors argued that gastric freezing is a simple, safe, and effective treatment for duodenal ulcer disease. They presented results of animal studies and experience in human patients to support this assertion. Stomachs of test animals were frozen "rock-hard"; yet tissue damage was minimal. Patients experienced no serious side effects from the procedure. Stomach acid output was markedly reduced in both humans and animals. Ulcer pain was immediately relieved, and radiographic healing of ulcers regularly followed. Because of gastric freezing, no surgery had been required on any patient with duodenal ulcer referred to Wangensteen since mid-l96l for elective operation. In addition, speculated the authors, because of its brevity, simplicity, and safety, the procedure could become accepted practice for treatment of outpatients, and so eliminate the need for hospitalization as well as surgery. For a scientific publication, this article is striking for its discursive and anecdotal style, as well as its enthusiastic tone.* The authors earnestly believed they had discovered a major breakthrough in the treatment of duodenal ulcer disease, and their writing conveys their excitement. They had a sound physiological rationale, extensive experiments in animals, and clear-cut results in humans. Over the next few years, every important assertion in this introduction of gastric freezing to clinical medicine was disputed, and practitioners became disen- chanted with the practice. In the meantime, however, several thousand gastric freezing machines were sold and thousands of patients underwent the procedure. DIFFUSION OF GASTRIC FREEZING: ADOPTION, EVALUATION, AND ABANDONMENT Wangensteen's presentation at the American Surgical Association meeting and publication in the Journal of the American Medical Association in the spring of l962 created a sensation among the public as well as the medical profession. Many local newspapers printed accounts of Wangensteen's new treatment, and Time maga- zine carried an article on gastric freezing on May l8, l962. *Franz Ingelfinger, abstracting this article for the l962-63 Year Book of Medicine, commented: "Is this the new approach to ulcer treatment everybody has been yearning for? The report is certainly dramatic and stimulating, but the nature of the presen- tationâdiscursive, fragmentary, and with tables that are hard to comprehendâprecludes meaningful editorial comment" (p. 488).
l77 Wagensteen refused an invitation to appear on NBC's "Today" show because he did not feel that would be appropriate, but the new procedure was also discussed on television. Wangensteen sought to disseminate his ideas and findings through professional meetings and publications. In the fall of l962, Wangensteen and his associates published equally impressive results in an ex- panded series of patients1^ and also presented their findings at the October meeting of the Surgical Forum. Around the same time, the American College of Surgeons prepared an instructional film describing the technique of gastric freezing. The public continued to be informed through an article in Today's Health in January l963, which appeared in condensed form in that same month's issue of Reader's Digest.16 By the end of l962, Wangensteen was inundated with requests for information and assistance from all over the United States and, indeed, the world. Swenko already had received more than 300 American orders for gastric freezing machines. At the time, the company had no distinct marketing activities and was unpre- pared for the flood of orders. At one time there was a backlog of nearly 200 unfilled orders, but production gradually geared up to a peak of 99 units per months. Several thousand physicians visited Swenko and Dr. Wangensteen to witness the procedure first- hand. One enterprising visitor from Texas later described proudly how he convinced the Swenko management to ship him a unit ahead of others.17 He wanted to try the procedure on out- patients in his rural clinic and reasoned with the Swenko people that if really large numbers of units were to be sold, the proce- dure would have to be proved outside university centers; his unit arrived the next week. After trying the procedure in 78 patients, he wrote a glowing report in early l963: We consider it certain that a real breakthrough has been made; that the resistent [sic] duodenal ulcer now can be brought under control; that gastrectomy for duodenal ulcer will henceforth rarely be required. While Swenko was the first and probably the dominant manufac- turer of gastric freezing devices, the devices did not have an exclusive market. Devices from at least two other manufacturers* are identified in the literature, but neither could be located today. According to records provided by Swenko, that company sold approximately l,500 machines in the United States and had received orders for 80 percent of this total by the end of l963. One *Shampaine Industries of New Jersey and Thermatrol Corporation of Indiana.
l78 writer estimated near the end of l963 that l,000 devices were in place and l0,000 to l5,000 procedures already carried out nationwide.18 Most published papers that identify manufacturers report use of Swenko devices, but at least one claimed technical advantages for another manufacturer's machines.19 A conservative assumption that the other two major manufacturers each sold one- third the machines sold by Swenko would bring the total distrib- uted in the United States to 2,500.* The diffusion of Swenko gastric freezing machines over time is represented in Figure l. The abrupt fall in orders after mid-l963 probably reflects in part competition from other manufacturers. Half the machines sold by Swenko went directly to hospitals; the remainder were divided evenly between physicians' offices and dealers, who presumably resold to both physicians and hospitals. The cost of the Swenko machine increased by several hundred dollars between l962 and l966, but most machines sold for approxi- mately $l,800. The number of patients who received gastric freezing treat- ments can only be indirectly estimated.t Several thousand patients are included in studies reported in the literature. If we assume that each machine treated only l0 patients, then 25,000 persons in the United States were treated with gastric freezing, and the number might well have been double that. Professional fees for gastric freezing varied widely, but some physicians allegedly charge the same fees as for a gastrectomy. 0 Anyone familiar with the history of treatment for duodenal ulcer disease would have had reason to be skeptical of claims made for gastric freezing at professional meetings and in the popular media in l962. Peptic ulcers have been treated with an enormous variety of drugs and nostrums, and there even were claims of success for agents now used to provoke stomach acid secretion or now considered dangerous in patients with ulcer disease. Some responsible observers were appalled by the early, rapid, and uncritical adoption of the new treatment by so many physicians.22 At least one editorial in l96320 and several more in l96423/24 described the procedure as experimental, urged caution, and empha- sized the need for careful clinical evaluation. *A newspaper article in the New York Times, October 29, l963, page 38, states that 5,000 machines had been sold, but that seems exaggerated to this author on the basis of other available evi- dence. '''The number of gastric balloons sold would have been a useful index, but the major supplier before l966, Pioneer Rubber Company, was unable to provide this information.
20r CO LU 2 o u 1E 10 < 1962 1-3 4-6 7-9 10-12 1-3 4-6 7-9 10-121-3 4-6 7-9 10-12 > 1964 '62 '62 '62 '62 '63 '63 '63 '63 '64 '64 '64 '64 100r > 50 o < 1962 1-3 4-6 7-9 10-12 1-3 4-6 7-9 10-12 1-3 4-6 7-9 10-12 > 1964 '62 '62 '62 '62 '63 '63 '63 '63 '64 '64 '64 '64 FIGURE l Sales of gastric freezing machines by lead- ing manufacturer. Based on date orders received by Swenko, Minneapolis, Minn. l79
l80 Beginning in l963, the physiologic rationale and safety of gastric freezing were questioned. Researchers using experimental dogs discovered that the procedure did not really freeze the entire stomach; the "rock-hard" feel reported initially was due to a thin shell of gastric contents surrounding the balloon. As it turned out, the absence of truly frozen tissue was fortu- nate because where patchy freezing did occur, necrosis followed.26,27 In July l963, Wangensteen and his colleagues extended their earlier work.28 Other clinical reports in l963 were generally favorable because of marked symptomatic relief.29 However, at least one early investigator failed to detect clini- cal improvement,33 and noteworthy side effects began to be documented, including gastric ulceration, bleeding which required transfusion,3 electrocardiographic changes, burnlike damage to gastric tissue, pneumonitis, and perforation of the lower esophagus due to faulty placement of the balloon.35 Questions were raised about the physiologic effects of gastric freezing,36 and one research group was unable to document any association between symptomatic improvement and changes in gastric acid secretion. Physicians attending the American College of Gastroenterology meeting in October l963 and the Southern Surgical Association meeting in December l963 expressed diverse opinions regarding the value and risks of gastric freezing and growing appreciation of the technical complexity of what initially appeared to be a simple technique.37,3fl For example, the extent to which stomach temperature would drop depended not only on the temperature of the alcohol and duration of the procedure, but also on volume and shape of the balloon, balloon wall thickness and material, flow rate of the alcohol, and blood flow to the stomach.18,38 Some also noted that the duration of symptomatic improvement was vari- able,37,38 and some patients required repeat freezings. In l964, for the first time, published reports concluded that gastric freezing was not worthwhile because acid suppression was limited or unrelated to pain relief, symptomatic improvement was short-lived or due to placebo effect, and important risks attended the procedure. , Several critical review articles empha- sized the need for controlled and comprehensive evaluations of the method.22,43 Others remained more neutral in their overall assessment of the procedure, but stressed the limited evidence to date44 and potential dangers of the procedure. 18 ' 37,45 Gastric ulceration or bleeding occurred in l out of l0 patients, 21,45-48 and there were two deaths and one near-fatality reported that year due to gastric ulceration following the procedure.18'37,4" There were additional reports of cardiac ischemia and electro- cardiographic abnormalities related to gastric freezing, which persisted in some patients beyond the duration of the procedure. '
l8l A survey reported in l964 of 83 physicians and institutions who had purchased gastric freezing machines found some patients had been exposed to substantial risks without regard even for the indications for the procedure.18 Nine percent of respondents performed gastric freezing as an outpatient procedure and an equivalent percentage did not require history of medical intract- ability before doing the procedure. What was developed and promoted as a last, safe resort before surgery was by this time not only evidently risky and questionably efficacious, but also being indiscriminately applied by some. Reports favorable to gastric freezing also continued to appear in l964. Wangensteen and his associates published tem- perate extensions of their clinical series showing continued excellent clinical results, though 25 percent of patients re- quired refreezing and there were a few minor complications.50" The authors contended that gastric freezing produced immediate and complete symptomatic relief in 85 to 90 percent of patients and offered a direct rebuttal of criticisms leveled against the procedure. While he still had faith in gastric freezing, Wangensteen realized the practice had burgeoned and suspected it was being applied sloppily. Papers from his group in l964 stressed the importance of careful technique and the need for further evaluation. Others also published favorable reports in l964, but all stressed risks as well as benefits and urged limit- ing the procedure to medical centers where patients could be properly supervised by experienced personnel. ^~57 During l964, variations in technique became an important arguing point for proponents of gastric freezing. 0"â¢ Wangen- steen and his colleagues continued to experiment and vary the treatment duration, temperature, flow rate, nozzle opening, balloon coolant, balloon shape, and ancillary measures used in the procedure. At one point, an adjunct intravenous vasocon- strictor was touted,58 only to be discarded quietly in a footnote 6 months later.59 Articles by Wangensteen and his co-workers commonly included some variation in technique applied at different times in the reported series or had addenda describing the latest adjustments.I4,50-52,58 Some procedural and equipment variations appeared minor, but any might be sufficient to explain differences in side effects or clinical results obtained by different investi- gators. An associate of Dr. Wangensteen at one point invoked an admonition he attributed to Claude Bernard: "Technic," said the great physiologist, "is everything."59 In the midst of the controversy, Wangensteen also reminded his colleagues of the sluggish professional acceptance accorded some earlier advances in gastric surgery.58 Clinical use of gastric freezing passed its zenith in l964. To be sure, articles discussing the physiology and physical
l82 effects of gastric freezing continued to appear60"64 and there were many more reports of complications in patients and experi- mental animals.65"73 In some clinical reports published in l966 and l969, the authors state they had discontinued gastric freezing in l964. 74,75 Several panelists discussing gastric freezing at the American College of Gastroenterology meeting in October l964 made it clear they had abandoned clinical use of gastric freezing at their institutions earlier that year.59 Evidence of declining interest in clinical application parallels the drop in orders for new machines received by the leading manufacturer after l963 (Figure l). By l966, clinical use of gastric freezing in the United States had spent its course, though units still were being purchased overseas. One editor introduced a l967 article on gastric freezing's effects on the heart by apologizing, "Though the clinical use of hypothermia for duodenal ulcer has 'come and gone,' a study ... is of interest for the record."73 A review of literature by the author produced 36 clinical reports on gastric freezing published between l962 and l969 (Table l), though a few publications report the same study. The trend over time was toward more negative appraisals of the technique (Table 2). Eight studies with control groups or with double-blind, randomized designs were identif iedl>1, 57, 6<+,76-80 and five of these appeared in l966 or later.64,77~80 Dates when patients were administered gastric freezing are provided in three of these papers; in one**0 the study began in l963 and in the other two 6tf,'9 the last patient was treated in l964. None of the studies published after l965 reached conclusions favorable to gastric freezing, but of the three double-blind studies published in l964 and l965,41, 57'75 two concluded that clinical improvement was probably related to gastric freezing.5 ,6 Many physicians became disenchanted with gastric freezing without compelling evidence in the literature that the procedure was inefficacious, though questions had been raised; most likely, the substantial morbidity and occasional mortality evident by the end of l964 persuaded many to abandon gastric freezing. Evaluations of clinical efficacy published after l965 only rein- forced those decisions. Interestingly, only one group of investi- gators published one article with conclusions favorable to gastric freezing57 and later wrote a second article with unfavorable conclusions.79 In l966, Dr. Wangensteen lost support from the National Insti- tutes of Health for research in gastric freezing. He remained convinced the procedure was promising and obtained funds from the other sources to continue his work. More than l0 years after he first proclaimed clinical success with gastric freezing, Dr. Wangensteen maintained the procedure was worthwhile, and,
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l85 TABLE 2 Overall Evaluation of Gastric Freezing by Clinical Studies Evaluation Qualified Qualified Year Favorable Favorable Neutral Unfavorable Unfavorable l962 l963 l964 l965 l966 l967 l968 l969 Double-blind, randomized study. Study with control groups. "apart from a note of optimism," did not think there was anything inaccurate in any of his papers. Further refinement of technique and research in dogs culminated in a l972 research report from Dr. Wangensteen)s laboratory. Here the authors conclude: The technology of the gastric freeze procedure has now progressed sufficiently to justify prospective controlled clinical studies of its effectiveness in the management of some aspects of the peptic ulcer diathesis by inter- ested, qualified, and critical investigators. One can only wonder how the course of medicine's misadventures with gastric freezing might have been different had so circum- spect a conclusion been offered l0 years earlier. OBSERVATIONS AND ANALYSIS This case study has attempted to trace the complete life cycle of a medical innovation, from inception through dissemination,
l86 and finally, abandonment. In gastric freezing, a medical practice was abandoned not because a newer and better alternative became available, but because the practice itself turned out to have more drawbacks than benefits. Gastric freezing was not a crackpot scheme generated on the fringe of medicine. It began as a scientific insight by a skilled and respected surgeon who developed the idea on the basis of physiologic reasoning and substantial laboratory experi)- ence. In retrospect, Dr. Wangensteen did admit to excessive enthusiasm at the beginning. If he and his colleagues had further fault, it was their reluctance to yield a beautiful con- cept in the face of ugly facts presented by outsiders. Other medical innovators have also been known to persist in their convictions when the majority disagrees. Vineberg contin- ued to champion internal mammary artery implants for angina pectoris years after controlled studies and expert consensus had denied their value. Perhaps the same independence and drive that allow the innovator to be a pioneer also enable him to ignore the collective wisdom of his colleagues. The fact that a creative individual leads the way for one beneficial innovation lends no assurance that future judgments will be correct. In his pathbreaking study of resistance to medical innovations written 50 years ago, Stern recounts how nineteenth century advocates of antisepsis bitterly opposed the later idea of surgical asepsis.85 Factors that help explain the early, rapid dissemination of gastric freezing include Dr. Wangensteen"s stature, confidence, and optimism, the high prevalence of duodenal ulcer disease and its natural tendency toward exacerbations and remissions, morbidity and mortality of alternative surgical treatments, promotion in the public media, ease with which physicians could learn to perform the procedure, and the opportunity for financial gain by physicians. A respected surgeon advocating a nonsurgical treatment may be especially credible, and the allure of nonsur- gical treatment appealed to well-informed physicians as well as to the public. In the latter part of l964, a prominent gastroen- terologist assessed the status of gastric freezing in an editorial and concluded, "At this time there is no justification for its general adoption by the medical profession."23 At a meeting of the American Gastroenterological Association the very next month, the same physician responded to his own question, whether he would consider gastric freezing for himself: Being fundamentally a physiologist, and knowing the dire circumstances of losing not only an important part of my gastrointestinal tract but having its continuity disturbed, I think I would subject myself to this procedure. ... If
l87 relief of symptoms is due to a placebo effect, I think I would be just as susceptible to the psychological effect. I certainly would not anticipate that my gastric secretion or mobility would be significantly altered or even that my crater might heal. Just last week I saw a patient who still had a crater six weeks after having this procedure, but he denied any symptoms whatever. I honestly think I would probably give it one try. In gastric freezing, thousands of ulcer sufferers saw a quick, easy, and safe means to gain relief. Many had undoubtedly been told they faced surgery when news of the breakthrough appeared on television and in newspapers and magazines across the country.* As a member of the medical school faculty, Dr. Wangensteen received no fees for any of his services. However, some physicians apparently felt justified charging patients the same fees for gastric freezing as they did for surgery, so as to suffer no sacrifice of personal income when they substituted the simpler procedure. Other characteristics of the development and dissemination of gastric freezing also deserve comment. Commercial interests were not prominent in promoting this innovation; the principal manufacturer was unprepared for the early surge in demand for gastric freezing machines. Swenko printed brochures and enter- tained many medical visitors, but never mounted any direct marketing effort. Technical entrepreneurs in industry are characteristic of many medical innovations,86'"7 but gastric freezing had none. Essentially, gastric freezing for duodenal ulcer was a new application of existing refrigeration technology. Once the clinical advocate conceived the idea, technical exper- tise was available to produce desired equipment modification in a matter of weeks. Early laboratory and applied clinical research was supported by the National Institutes of Health and private foundations. The 2 years that elapsed between initiation of directed research and general availability was shorter than all but 2 of 25 medical innovations reviewed recently by the President's Biomedical Research Panel, and those two involved drugs.87 The development of gastric freezing is an example of ideal collaboration between government-supported researcher and private-sector engineer, *Some years earlier, public clamor for a new medical device similarly followed an article in the Saturday Evening Post about an apparatus to measure oxygen in newborn incubators. The device had been available for several years, but high volume sales began with that magazine article.
l88 between science and industry. Except that the procedure proved to be risky and without benefit, it would be a marvelous success story. Beyond the unwarranted enthusiasm of early proponents, two features of the diffusion of gastric freezing are disturbing. First, at least some early adopters applied the innovation with- out regard for the clinical criteria recommended by its pro- ponents. No responsible authority had suggested use of gastric freezing in patients who responded to medical treatment, yet one early survey found that l in ll users did not require a history of medical intractability. Even if gastric freezing were a worthwhile alternative to surgery, routine use in patients with less severe symptoms could not be justified. The value of any medical technology is inseparable from the clinical context in which it is applied; procedures that may be beneficial in a particular set of circumstances are liable to be used as well where they are not worthwhile. The second and most disheartening aspect of this study is the minimal relation between properly designed clinical trials and the diffusion process, a problem that might be described as the inefficacy of efficacy studies. Gastric freezing was purported to relieve subjective symptoms and to reduce objectively measured gastric acid. The placebo effect is a concern when any subjec- tive feeling is involved and especially with pain. Variability in gastric acidity among normal persons and the real possibility of falsely low measurements further confounded efforts at objective assessment. The majority of clinical studies of gastric freezing were observational (Table l), and there are problems with the design and comparability of those studies that were controlled.8Â® Responsible observers recognized early the need for randomized, double-blind studies to evaluate gastric freezing. In fact, such a well-designed multicenter trial was initiated in l963.80 Multicenter studies are diffi- cult to organize and conduct, and properly designed clinical trials often require long-term patient follow-up. Results of this major study did not appear in the literature until l969. The report was unequivocal in its negative conclusions, but of little practical consequence, as if a marble tombstone were erected over the grave of a patient already several years deceased. Shortcomings in design and delays in completion and publi- cation of well-controlled studies are only part of the problem. Clinical evaluations published in the medical literature are only one determinant of clinical practice. Information from colleagues may be more influential than published articles on a physician's awareness of new findings and choice of practice. Other influences may outweigh even compelling evidence from
l89 clinical evaluations. Chalmers cites a number of examples where physicians continue to use treatments despite well- controlled trials demonstrating they are worthless or harmful.91 In the second volume of Controversy in Internal Medicine, pub- lished in l974, the editors review the status of the 23 controversies included 8 years earlier in their first volume. Ingelfinger summarizes: The lesson appears both clear and discouraging: some controversies in Internal Medicine persist for years and years; others subside gradually as interest wanes. Very few if any appear to be resolved by some elegant study that dramatically demolishes one side or the other.91 The lament does not end there; when finally published, an elegant study may be too late, and, even if timely, it may have little effect on medical practice. POLICY LESSONS In general, the desirability of disseminating a medical inno- vation depends on five features: l. Technical practicabilityâperformance characteristics of the new drug, device or equipment. 2. Safetyâdegree of hazard to the patient, provider, and population at large, in the short run and long run. 3. Clinical efficacyâcomparative effectiveness in specified clinical circumstances; measured effect may range from proximate influence on care to ultimate effect on health.92 4. Costânet resources required to utilize the innovation. 5. Societal effectâimpact, if any, on social values and institutions. Each of these elements is typically unknown to some degree when an innovation is introduced, and sometimes for considerably longer. A dichotomous classification of an innovation as either "experimental" or "established" fails to do justice to any one of these features, much less to the combinations that may occur. If a new technology is on balance beneficial and is adopted, that constitutes appropriate use. If an innovation turns out, all things considered, to be of negative value, and it is shunned, that is appropriate nonuse. Obviously, two complemen- tary types of error are possible: overdiffusion of a bad technology and underdiffusion of a good technology (Figure 2). Because the clinical value of any new medical technology is
l90 Dissemination Adopted Not adopted Net value of innovation Good Bad Appropriate use Error of underdiffusion Error of overdiffusion Appropriate nonuse FIGURE 2 Possible consequences of a medical innovation. unknown, there is always some finite risk at the outset of committing each type of error. This dual risk is reflected in the contradictory functions of different government agencies; some, such as the National Institutes of Health and National Science Foundation, encourage development and dissemination of new medical practices, while others, such as the Food and Drug Administration, serve to retard the availability of new practices. Most case studies of medical and other innovations have con- centrated on triumphs, "good" innovations that sometimes were delayed in their full development and dissemination.87,93 These studies attempt to discern the causes of delay or "lag periods" in diffusion and the reasons for successful dissemination. Thus, they limit themselves to the upper two cells of Figure 2, and for this reason, even taken collectively, they may be misleading. For example, an enthusiastic advocate, identified as important in many cases, is characteristic not simply of good innovations, but of widely disseminated innovations, whether good or bad. Case studies, such as gastric freezing, introduce the complementary risk of overdiffusion, a concern that should also guide policy. However, any general policy that retards dissemination of new innovations and so reduces risk of overdiffusion simultaneously increases risk of under- diffusion, and vice versa. Recent federal legislation aims to make future episodes such as gastric freezing less likely. The Medical Device Amendments of l976 (P.L. 94-295) empower the Food and Drug Administration to require premarket approval of medical devices. The principal rationale for this authority expressed in the statute is consumer protection. Devices classified in the most restrictive cate- gory, Class III, must satisfy a premarket test procedure to establish safety and efficacy. This premarket test clearance
l9l entails well-controlled investigations, but, unlike clearance for new drugs, does not necessarily require clinical investi- gations. Absent from the legislation is any concern with cost implications of new devices. Also, the FDA devices legislation does not deal with possible improper use of an innovation after it has been approved. It is too early to assess the effect of this new authority. Since the number of devices covered by the legislation is enormous, the FDA will need to establish some priorities to guide its activities. The extent to which the law will retard premature dissemination of unproved devices depends on how it is implemented, i.e., FDA's readiness to classify devices in the most demanding category, the nature of research requirements to establish efficacy of each type of device, and the agency's willingness to delay marketing in the face of pressure from business, the public, and the medical profession. One lesson from gastric freezing with regard to safety is that the earliest reports may be misleading, and it would be unwise to rely too heavily on any single research team. In terms of efficacy, clinical evaluation may be difficult and time-consuming, but extrapolations from nonclinical laboratory studies are liable to be erroneous. Well-designed and carefully conducted clinical trials are essential, but it may be possible to obtain useful information more efficiently with study designs other than randomized, double-blind.94 Issues of cost and appropriate utilization, outside of FDA's authority, are to some extent within the ambit of other health regulatory and planning activities, such as PSRO and utilization review, certificate-of-need laws, rate-setting commissions, and health systems agencies. At present, no single body both has responsibility for assessing all five features of medical innovations and authority to intervene in the diffusion process, either to speed or to slow it. If such a body did exist, it would be handicapped by inadequacies in evaluation methods and meager knowledge about the effect of different types of control over diffusion. The physician remains the principal decision-maker regarding use of most medical innovations. Physicians will inevitably make mistakes, but they should not err for the wrong reasons, such as misplaced reliance on fragmentary information, succumbing to the force of authority rather than depending on the strength of evidence, suspicion of population-based studies, ignorance of the pitfalls and requirements for statistically and scientif- ically valid clinical research, a need to have the latest gadget, a desire to achieve prestige, defend a reputation, or gain financially. Every decision to use or not to use a medi- cal innovation entails some chance of success and of failure,
l92 but it should be an informed judgment, based on the best evidence available, and with the interests of patients foremost. Gastric freezing posed substantial risk to patients, and decisions to adopt or abandon the innovation properly could be weighed according to potential harm and possible benefit to the individual. More troubling are decisions that may require trade-offs between what may be best for the individual patient and what is best for society or for patients collectively. The possible adverse consequences of medical innovations for the individual are safety and health hazards and the possibility that use of the innovation delays or precludes other, more beneficial interventions. From the point of view of society, an innovation may have long-term risks (such as environmental consequences or genetic damage) and typically entails some financial cost. As we collectively assume a greater proportion of the costs of health care and as these costs continue to rise, the financial implications of medical innovations increasingly become a societal concern. Every decision, whether explicit or implicit, to apply or withhold a medical innovation, is in effect a resource allocation decision. Physicians should remain primarily individual patient advocates, but they must also become cognizant of societal interests, of the interests of all patients. Fortunately, the interests of the individual patient and of society frequently converge. Gastric freezing was good for neither. Many medical interventions benefit the individual and represent worthwhile social investment. But there remains a perplexing group of innovations, exemplified recently by computerized tomography, whose major drawback is high cost, whose safety is relatively ensured, and whose ultimate clinical efficacy is unknown.95 With this group we are just feeling our way.9 6 Gastric freezing reminds us that proposals for public policy toward medical innovations should consider all four possible consequences of an innovation. Physicians should be trained to be descerning in their interpretation of clinical findings and should be sensitive to societal as well as individual costs and benefits. Appropriate and timely clinical trials are essential for informed decision-making. We need to devise strategies for making decisions in the face of uncertainty accompanying new innovations. Logically, this should include surveillance and evaluation both before and after an innovation is generally available. We need better understanding of the diffusion process and especially of characteristics that lead to non- adoption of relatively good innovations and excess use of relatively bad innovations. Finally, we need more effective means of hastening or retarding the diffusion of medical practices, and the ability to do both wisely.
l93 APPENDIX: CAPSULE HISTORY OF GASTRIC FREEZING Background l924 Prout l953 l958 Kay Wangensteen Conception l959 Initial research l960-6l and develop- ment Clinical availability l962 Wangensteen Wangensteen Wangensteen Swenko Corpora- tion Dissemination l962-64 Proves stomach acidity due to free HCl Augmented histamina test to measure gastric acid production Introduces gastric hypothermia for control of gastrointestinal bleeding Describes possibility of gastric freezing to treat peptic ulcer First human application in October l96l Success announced at professional meeting in May; widely publicized in popular media Full production capability by second half of year Over l,000 machines sold by latter part of l963, l0,000- l5,000 treatments Substantial risks to patients become evi- dent by end of l963 Unfavorable conclusions reached by some investigators in l964 because of lack of efficacy and high risk
l94 Abandonment l964-66 Physicians begin to abandon procedure in l964 Later evaluation l967 Adverse evidence continues to accumulate l965-66; advocates defend value of procedure, continue technical improvements Clinical use effectively ends in U.S. by l966 Estimated 2,500 machines sold in all; 25,000 treatments More negative evaluations published l967-69 Research use continues, deemed clinically promising in l972 REFERENCES Walker, O. "Chronic duodenal ulcer." Chapter 54 in Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. M. H. Sleisenger and J. S. Fordtran, eds. Philadelphia: W. B. Saunders Co., l973. U.S. Department of Health, Education, and Welfare. Limitation of Activity and Mobility Due to Chronic Con- ditions USâ1972. DHEW Publ. No. (HRA) 75-l523, November l974. U.S. Department of Health, Education, and Welfare. Mortality Trends for Leading Causes of Death USâl950-69. DHEW Publ. No. (HRA) 74-l853, March l974. Silen, William. "Peptic ulcer." Chapter 287 in Harrison's Principles of Internal Medicine. 8th ed. G. W. Thomas, R. D. Adams, E. Braunwald, K. S. Isselbacher, and R. G. Petersdorf, eds. New York: McGraw-Hill Book Co., l977.
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