Kidney stones and lithotipters: critical analysis of the introduction of extracorporeal shock wave lithotripsy into Canada Lawrence C. Wiser, MD, MHSA; Richard H.M. Plain, PhD; John B. Dossetor, MD, PhD, FRCPC It is possible for a nonpharmaceutical medical innovation to enter the mainstream of the health care system without its efficacy and effectiveness having first been established by means of a randomized controlled trial (RCT). The result of this omission may be the discreditation and abandonment of the technology or procedure but not before precious resources that could have been better used elsewhere in the health care system are absorbed. A possible example of such a misallocation of resources is the introduction into Canada of extracorporeal shock wave lithotripsy (ESWL) for the treatment of urolithiasis. We review the development and diffusion of ESWL and recommend ways in which the deficiencies in regulating the introduction of new medical technologies can be corrected.

II est possible qu'une innovation medicale non pharmaceutique s'installe dans le courant du systeme des soins de sante sans que son efficacite ait d'abord ete prouvee par essai contr6le aleatoire. Le resultat de cette lacune peut entrainer le discredit ou l'abandon de la technologie ou technique, mais dans l'intervalle elle aura absorbe de precieuses ressources qui auraient ete mieux utilisees ailleurs dans le reseau des soins de sante. Un exemple eventuel de cette mauvaise affectation des ressources est l'introduction au Canada de la lithotripsie extracorporelle par onde de choc pour le traitement de l'urolithiase. Nous examinons le developpement et la diffusion de cette technique et recommandons des moyens de corriger les lacunes inherentes a la reglementation relatives a l'introduction des nouvelles technologies medicales.

A peculiarity of medicine is that the diffusion of new treatments and technologies can precede rigorous evaluation. According to McKinlay' a medical innovation may go through seven stages: (1) promising report, (2) professional and organizational adoption, (3) public acceptance

and state (third-party) endorsement, (4) standard procedure and observational reports, (5) randomized controlled trial (RCT), (6) professional denunciation and (7) erosion and discreditation. During the final stage the innovation may be totally discredited or simply fall out of widespread use, to be replaced by

Dr. Wiser was a policy adviser to the Manitoba Department of Health, Winnipeg, and is now a private practitioner in Regina. Dr. Plain is professor of economics and Dr. Dossetor director of the Joint-Faculties Bioethics Project, University ofAlberta, Edmonton.

The opinions expressed herein are those of the authors and not necessarily those of the Manitoba Department of Health, the University of Alberta or the Joint-Faculties Bioethics Project. Reprint requests to: Dr. Lawrence C. Wiser, cdo Joint-Faculties Bioethics Project, 222 Aberhart Nurses Residence, 8220-114 St., Edmonton, Alta. T6G 2J3 -

For prescribing information see page 1376

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another innovation,2 and the entire cycle may begin again.

Ideally, the second and third stages (including incorporation of the innovation into the fee schedule of the provincial government health insurance plan) should occur only after an RCT has established the efficacy, effectiveness and safety of the procedure. (We apply the framework described by Sackett3 in our use of "efficacy" and "effectiveness" to ask respectively Can it work? and, once implemented, Does it work?) This sequence of events now takes place in the drug industry to minimize the chances of a drug scandal similar to that of thalidomide. Chalmers4 noted that new drugs are subjected first to large-scale RCTs and then to monitoring once the drugs have been deemed suitable for therapeutic use. Unfortunately, the reform of the drug industry has not been extended to the rest of the health care system. This overview of the development and diffusion of extracorporeal shock wave lithotripsy (ESWL) in the treatment of urolithiasis provides additional evidence of the need to reform how nonpharmaceutical innovations are regulated in Canada.

History of ESWL During the middle to late 1970s a technique appeared imminent that would represent a quantum leap forward in urology:5-7 shock waves would reduce kidney stones to fragments, to be passed out of the body in the urine. ESWL arrived in the early 1980s.8A9 The technique was greeted with an avalanche of support because it was felt to be safer'0- 2 and more cost-effective'3 '4 than the conventional treatment of urolithiasis. Enthusiasm became so great that in 1984 its creators announced that "a significant enhancement in [renal] function up to 110%" had been achieved,'5 a claim refuted in the literature 4 years later.'6 Clearly the ESWL "tide" was flowing and was at the beginning of McKinlay's stage 4. Even before this stage the technology had been diffusing rapidly throughout the health care systems of North America. Indeed, this form of treatment was being recommended as "a primary treatment for urolithiasis whenever applicable".'7 The first hint that all might not have been well came in mid-1985, when Kaude and associates'8 reported problems in the renal morphologic and physiologic features immediately after ESWL. The paramount finding was "a loss of corticomedullary differentiation" involving the renal parenchyma, which prompted the authors to remark that "loss of corticomedullary junction occurs with a variety of renal diseases including glomerulonephritis, acute tubular necrosis, end-stage chronic renal failure, 1300

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renal artery stenosis and transplant rejection". They concluded that ESWL should be added to the list. These findings have since been amplified.'9-21 Williams and collaborators22 demonstrated morphologic and pathophysiologic renal changes, initially considered to be only temporary but present in the kidneys 17 to 21 months after ESWL. More recently, Williams and Thomas23 found that renal function progressively decreased over 4 years after ESWL. Perhaps the most distressing findings associated with the technique were hypertension24 (a condition recently found to be non-renin-dependent25) and perirenal hematoma,26 which prompted Knapp and Kulb26 to withdraw their endorsement of outpatient lithotripsy with the use of the Model HM3 Lithotripter (Dornier Medical Systems Inc., Toronto).27 The appearance of second-generation lithotripters, such as the Siemens Lithostar (Siemens Electric Ltd., Toronto), has not improved matters. Although the number of "bioeffects" associated with ESWL has been reduced by 50%,2829 more shock waves are required to break up calculi, and more secondary treatments are necessary.30 The issues of effectiveness and safety have now spilled over into McKinlay's stage 5. The US Food and Drug Administration has asked for a postapproval study plan of the treatment of urolithiasis with ESWL.3' 32 In Ontario an RCT has been in progress since April 1989:33 asymptomatic patients with kidney stones are assigned to receive ESWL or another treatment. In short, RCTs are being used to address the issues of effectiveness and safety after the innovation has been widely diffused throughout the system, after tens of millions of dollars have been spent on lithotripters and thousands of people have been treated. It is premature to judge the results of these trials. However, it is important to note the points made by Drummond, Stoddart and Torrance34 and Feeny, Guyatt and Tugwell:2 the economic evaluation of health care technologies, procedures and programs is most useful and appropriate after their efficacy and effectiveness have been established; the use of economic resources to find the least costly way of introducing a medical innovation that turns out to be ineffective simply exacerbates the misallocation of resources.

Reforming the system for evaluating medical innovations Federal regulation Although the responsibility for health care is a provincial one35 much of the blame for improper implementation and diffusion of health care technologies lies with the federal government. Many of the

assume that a provincial government or college of physicians and surgeons should regulate new medical technologies and ensure that they provide efficacious, effective and safe services to patients. Our experience in this regard has been negative in its purchase of two lithotripters. The No manufacturer of a device or person who has imported Alberta, despite ESWL elsewhere leads us to believe of RCTs of lack into Canada a device for sale shall sell the device unless in Alberta are generalizable. findings that the tests have been conducted in respect thereof and the tests When the registrar of the College of Physicians indicate that the nature of the benefits claimed to be attainable through the use of the device and the perfor- and Surgeons of Alberta was approached he indicatmance characteristics claimed for the device are justified ed that the Council of the college "has not made a as shown by evidence available in Canada to the manufac- study into whether lithotripters are efficacious, effiturer or the person importing the device. cient or safe" (Dr. Leroy E. le Riche: personal communication, 1989). There are still questions for answers. Who is responsible for quality begging effectiveefficacy, the The onus of establishing assurance (defined as confirmation that a medical the on ness and safety of a device is therefore will improve patient health if applied technology of manufacturer. This was confirmed by the minister in the Canadian health care system? appropriately) national health and welfare (Perrin Beatty: personal ESWL, where is the link between In of case the communication, 1989): "The Department of Nationestablished (i.e., through RCTs) quality scientifically al Health and Welfare does not approve medical health care costs? Why do public and assurance devices or the associated technologies. Rather, it is for services when the pay plans insurance health the manufacturer's responsibility to ensure that medshown to be efficaused has not been technology ical devices which he sells are safe and efficacious and safe? Is current way of the effective cious, when used as directed." medical innovations with nonpharmaceutical dealing The problem is compounded by the definition given the from an ethical perspective, acceptable of a new device in section 32 of the regulations as "a of uninthe interests to protect on physicians onus device listed in the table to this part".38 The "table" consumers? formed comprises contact lenses "designed or represented for prolonged wear", menstrual tampons and "any device designed to be implemented into the tissues Recommendations or body cavities of a person for thirty days or more". 0 Legislation should be enacted or amended Alhough there is limited room for interpretation of section 32 by the Health Protection Branch the and its interpretation by the Health Protection foregoing is seen to be what is "on the books" in any Branch be ratified such that no new medical device may be offered for sale in Canada before its efficacy Canadian law library. By statute lithotripters do not qualify as new and effectiveness in the treatment of patients has devices and therefore do not need to undergo clinical been established through an RCT. If such proof is trials before being offered for sale in Canada. Any not available patients should be treated only if they device not deemed by statute to be new (i.e., not are participating in some form of research protocol present in "the table to this part") enters the that incorporates random assignment into experiCanadian health care system under section 14 of the mental and control groups. If the research protocol regulations, which does not require premarket re- were undertaken when a new technology was introview by the Health Protection Branch but, rather, duced (and before coverage by medically uninplaces the onus on the manufacturer to prove the formed media) many of the ethical problems related to RCTs could be obviated. efficacy, effectiveness and safety of the device. As far back as 1975 Chalmers40 argued strongly Booth39 described such a paradigm as "an ethical no-man's land where the interests of academic that such a protocol be adopted, apparently to no science and business collide". Yet we are still unable avail. The propensity of physician-investigators "to to answer scientifically the questions Does ESWL err in the direction of overestimating the potential (for renal calculi) improve the patient's health sta- benefits of therapy" has been noted by Bunker, tus? Should ESWL have been adopted by the Can- Fowles and Schaffarzick,4' who stated that "overuse of unproved medical interventions has immediate adian health care system in the first place?'8-27 and urgent implications for distributive justice.... Purchase of care that is ineffective or of undocuProvincial regulation mented efficacy for some patients will almost cerGiven the constitutional responsibility of the tainly result in failure to provide effective care to provinces for health care it is not unreasonable to other patients." Others have agreed with this inter-

current problems are rooted in section 14 of the Medical Devices Regulations,36 promulgated under the authority of the federal Food and Drugs Act.37 Section 14 states the following.

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pretation.42-48 Enthoven47 stated, in his Shattuck lecture of 1978, that "although recognizing the many difficulties in planning and executing a randomized control trial . . . innovations in medical technology should be thoroughly evaluated early before being put into widespread use". This recommendation would apply especially to the "big ticket items", devices usually embodied in some form within machinery49 or a frame (e.g., lithotripters), and would expand the definition of a "new device" in section 32 of the Medical Devices Regulations as well as the interpretation of that section by the Health Protection Branch. Such a provision would ensure that no new health care technology would be implemented without full knowledge of its effect on the health of patients. * The federal and provincial governments should establish centres where RCTs of new embodied technologies could be performed and the efficacy, effectiveness and cost-utility be assessed. The establishment of these centres has been called for by Bunker, Hinkley and McDermott,50 who envisioned an "authority capable of sophisticated statistical and economic analysis and empowered with authority and resources necessary to initiate and coordinate appropriate trials". More recently, in Canada, Stiller5' has called for similar revisions in the health care system. * No medical technology should be approved for nonexperimental use in a province unless it has been assessed by means of RCTs and its efficacy and effectiveness have been established. The role of the provincial colleges of physicians and surgeons and ministries of health in attesting to and enforcing such an edict should be established to minimize any administrative delays or overlap. * Special measures should be taken by each provincial college of physicians and surgeons and ministry of health to monitor the appropriateness of the use as well as the outcome of each medical device introduced into the system. * The federal and provincial governments, the colleges of physicians and surgeons and the major teaching hospitals in Canada should consider adopting the framework for evaluating health care technologies established by Feeny, Guyatt and Tugwell.2 This recommendation would ensure a comprehensive assessment of all facets of a medical technology both before and after its widespread diffusion.

Conclusions If the Canadian health care system is fortunate an RCT of the treatment of urolithiasis with ESWL will provide a sound scientific basis for its efficacy, effectiveness and economic benefits. If the worst 1302

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were to occur McKinlay's stages 6 and 7 would be experienced; this would force Canadians to write off most of the capital costs associated with ESWL and acknowledge the problems that a number of unfortunate people will have to endure as a result of their exposure to it. If the results of an RCT indicate that the current number of patients deemed suitable for ESWL should be significantly reduced the economic comparison of ESWL and surgery for the treatment of kidney stones will have to be redone to determine whether further investment in lithotripters is warranted. If the recommendations we have provided are followed in Canada we can be much more confident of the medical and economic merits of the technologies that are widely diffused throughout the health care system. This should be the objective of everyone interested in the quality assurance and costeffectiveness of our health care system.

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Milbank Mem Fund Q 1981; 59: 374-411 2. Feeny D, Guyatt G, Tugwell P (eds): Health Care Technology: E,ffectiveness, Efficiency and Public Policy, Institute for Research on Public Policy, Montreal, 1986: 57-67 3. Sackett DL: Evaluation of health services. In Last JM (ed): Public Health and Preventive Medicine, 11th ed, ACC, New York, 1980: 1800-1823 4. Chalmers TC: The clinical trial. Milbank Mem Fund Q 1981: 59: 324-339 5. Chaussy C, Eisenberger F, Wanner K et al: The use of shock waves for the destruction of renal calculi without direct contact [abstr]. Urol Res 1976; 4: 181 6. Brendel W, Chaussy C, Forssman B et al: A new method of non-invasive destruction of renal calculi by shock waves [abstr 125]. Br JSurg 1979; 66: 907 7. Chaussy C, Schmiedt E, Forssman B et al: Contact-free renal stone destruction by means of shock waves [abstr]. Eur Surg Res 1979; 11 (suppl 2): 36 8. Chaussy C, Brendel W, Schmiedt E: Extracorporeally induced destruction of kidney stones by shock waves. Lancet 1980; 2: 1265- 1268 9. Chaussy C, Schmiedt E, Jocham D et al: First experience with extracorporeally induced destruction of kidney stones by shock waves. J Urol 1982; 127: 417-420 10. Chaussy C, Schmiedt E: Shock wave treatment for stones in the upper urinary tract. Urol Clin North Am 1983; 10: 743750 11. US National Center for Health Services Research and Health

Care Technology Assessment: Summary of Safety and Effectiveness Data: Dornier Lithotripter, Model HM3, US Public Health Service, Rockville, Md, 1985: 9-15 12. Riehle RA Jr, Fair WR, Vaughan D Jr: Extracorporeal shock-wave lithotripsy for upper urinary tract calculi: one year's experience at a single centre. JAMA 1986; 255: 20432048 13. Lingeman JE, Saywell RM, Woods JR et al: Cost analysis of extracorporeal shock wave lithotripsy relative to other surgical and non-surgical treatment for urolithiasis. Med Care 1986; 24: 1151-1160 14. Aronne LJ, Braham RL, Riehle RA Jr et al: Cost-effectiveness of extracorporeal shock-wave lithotripsy. lJrology 1988: 31:

225-230 15. Chaussy C, Schmiedt E, Jocham D et al: Extracorporeal shock wave lithotripsy (ESWL) for treatment of urolithiasis. Urology 1984; 23 (5, suppl): 59-66 16. Lingeman JE, McAteer JA, Kempson SA et al: Bioeffects of extracorporeal shock wave lithotripsy. Urol Clin North Am 1988; 15: 507-514 17. Jantzen JPAH, Erdmann K, Wilbert DM et al: Management of urolithiasis: an analysis of 1,293 lithotripter procedures [abstr]. Tex Med 1986; 82: 37-43 18. Kaude JV, Williams CM, Millner MR et al: Renal morphology and function immediately after extracorporeal shock wave lithotripsy. AJR 1985; 145: 305-313 19. Von Schulthess GK, Forster EC, Jager P: Magnetic resonance imaging at 1.5 gadolinium-DTPA for the study of renal morphology and function after extracorporeal shock wave lithotripsy [abstr]. J Nucl Med 1986; 27: 577A 20. Bomanji J, Boddy SAM, Britton KE et al: Radionuclide evaluation pre- and post-extracorporeal shock wave lithotripsy for renal calculi. J Nucl Med 1987; 28: 1284-1289 21. Baumgartner BR, Dickey KW, Ambrose SS et al: Kidney changes after extracorporeal shock wave lithotripsy: appearance on MR imagining. Radiology 1987; 163: 531-534 22. Williams CM, Kaude JV, Newman RC et al: Extracorporeal shock wave lithotripsy: long-term complications. AJR 1988; 150: 305-313 23. Williams CM, Thomas WC Jr: Permanently decreased renal blood flow and hypertension after lithotripsy. N Engl J Med 1989; 321: 1269-1270 24. Lingeman JE, Kulb TB: Hypertension following extracorporeal shock wave lithotripsy [abstr 154]. J Urol 1987; 137 (4, pt 2): 142A 25. Williams CM, Thomas WC Jr, Bucci CM: Low-renin hypertension after extracorporeal shock wave lithotripsy [C]. JAMA 1989; 262: 1952 26. Knapp PM, Kulb TB: Extracorporeal shock wave lithotripsy induced perirenal hematomas [abstr 155]. J Urol 1987; 137 (4, pt 2): 142A 27. Knapp PM, Kulb TB, Lingeman JE et al: Extracorporeal shock wave lithotripsy-induced perirenal hematomas. J Urol 1988; 139: 700-703 28. Scharfe T, Wilbert D, Staritz M et al: 5,000 patients' experience with the second generation extracorporeal shock wave lithotripsy using the 'Lithostar' [abstr 256]. J Urol 1988; 139 (4, pt 2): 226A 29. US National Center for Health Services Research and Health Care Technology Assessment: Summary of Safety and Effectiveness Data: Siemens Lithostar Lithotripter, US Public Health Service, Rockville, Md, 1988: 12-16 30. Preminger GM: The changing face of lithotripsy: impact of

"second generation" machines [abstr 952]. J Urol 1989; 141 (4, pt 2): 405A 31. Stern SM: Extracorporeal lithotripsy: reports of adverse side effects generate "shock-waves" of concern. J Clin Eng 1989; 14: 331-336 32. Lithotripsy's link to hypertension debated; remains treatment of choice for kidney stones. Health Technol Trends 1989; 1 (10): 4, 6 33. Bruce A, Goodwin W, Rankin P et al: Final report, Minister's Advisory Committee on Lithotripsy, Govt of Ontario, Toronto, 1989: 12 34. Drummond MF, Stoddart GL, Torrance GW: Methods for the Economic Evaluation of Health Care Programs, Oxford U Pr, New York, 1987 35. Constitution Act 1867 (UK), 30&31 Vict, c 3, s 92(7) 36. Medical Devices Regulations, CRC, 1978, c 871, s 14 37. The Food and Drugs Act, RSC, 1985, c F-27, as amended RSC, 1985 (1st suppl), c 27, RSC, 1985 (4th suppl), c 42 38. Medical Devices Regulations, SOR/79-755 39. Booth W: Conflict of interest eyed at Harvard. Science 1988; 242: 1497-1499 40. Chalmers TC: Randomization of the first patient. Med Clin North Am 1975; 59: 1035-1038 41. Bunker JP, Fowles J, Schaffarzick R: Evaluation of medical technology strategies: proposal for an institute for health-care evaluation (second of two parts). N Engl J Med 1982; 306: 687-692 42. Hiatt HH: Lessons of the coronory-bypass debate. N Engl J Med 1977; 297: 1462-1464 43. Relman AS: Assessment of medical practices: a simple pro*posal. NEnglJMed 1980; 303: 153-154 44. Idem: The new medical-industrial complex. Ibid: 963-970 45. Perry S: The brief life of the National Centre for Health Care Technology. N Engl J Med 1982; 307: 1095- 1100 46. Inglehart JK: Another chance for technology assessment. N Engl J Med 1983; 309: 509-512 47. Enthoven AC: Shattuck Lecture - cutting cost without cutting the quality of care. N Engl J Med 1978; 298: 12291238 48. Plum F: Extracranial-intracranial arterial bypass and cerebral vascular disease. N Engl J Med 1985; 313: 1221-1223 49. Guyatt G, Drummond M, Feeny D et al: Guidelines for health technology assessment: therapeutic technologies. In Feeny D, Guyatt G, Tugwell P (eds): Health Care Technology: Effectiveness, Efficiency and Public Policy, Institute for Research in Public Policy, Montreal, 1986: 57-77 50. Bunker JP, Hinkley D, McDermott WV: Surgical innovation and its evaluation. Science 1978; 200: 937-941 51. Stiller CR: High-tech medicine and the control of health care costs. Can Med Assoc J 1989; 140: 905-908

New remedies There is nothing in the whole range of medical history, which shows so miserable a logic, and so false a philosophy, as the introduction of this multitudinous assemblage of new remedies, with the properties which are so confidently assigned to them. But then the fault and the error are, - not that the remedies are new, - but that the evidence of their value and efficacy is so utterly wanting. - Elisha Bartlett (1804-1855)

CAN MED ASSOC J 1990; 143 (12)


Kidney stones and lithotripters: critical analysis of the introduction of extracorporeal shock wave lithotripsy into Canada.

It is possible for a nonpharmaceutical medical innovation to enter the mainstream of the health care system without its efficacy and effectiveness hav...
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