Cost Issues in Transplantation

HORIZONS IN ORGAN TRANSPLANTATION

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COST ISSUES IN TRANSPLANTATION Paul W. Eggers, PhD, and Lawrence E. Kucken, MPA

Major clinical progress has been made over the past 30 years in the field of organ transplantation. These advances have stemmed in large part from an increased understanding of the immunologic reactions involved in graft rejections and improved clinical remedies to suppress the immune system's response to the transplanted organ. In particular, cyclosporine (CsA) has proven to be significantly more selective than other known immunosuppressive agents used prior to its approval in November, 1983. The introduction of CsA was associated with a rapid increase in solid organ transplantation. From 1984 to 1991, heart transplants in the United States increased from 346 to 2127, liver transplants increased from 308 to 2946, and pancreas transplants increased from 87 to 535. The number of lung transplants has increased from 11 in 1987 to 400 in 1991.14, 40, 41 Survival rates have also reached acceptable levels, with I-year patient survival rates of 95% for kidney, 80% for heart, 70% for liver and pancreas, and 75% for lung.4O However, owing to a plateau in the number of cadaver organ donors, combined with an ever-increasing number of persons on the waiting lists, transplantation is a de facto rationed procedure, As of the end of 1993, more than 26,000 persons were on the United Network for Organ Sharing (UNOS) transplant waiting lists, with more than 20,000 on the kidney list alone.4O In addition, the high cost of individual transplants and the media coverage of multiple failed transplants for single individuals has raised serious questions among policy makers about coverage of these expensive procedures when few persons clearly benefit from them." Despite the concern over the high cost of transplantation, little reliable information is available about the costs associated with organ transplants. This is due to a variety of reasons, including differing definitions of cost, restrictions on what The opinions and conclusions reached in this paper represent the views of the authors and do not represent policy perspectives of the Health Care Financing Administration.

From the Program Evaluation Branch, Office of Research, Health Care Financing Administration, Baltimore, Maryland

SURGICAL CLINICS OF NORTH AMERICA VOLUME 74· NUMBER 5 • OCTOBER 1994

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is reported as transplant costs, and reliance on individual transplant center data for estimates of transplant costs. This article attempts to put some of the transplant cost issues in perspective and to suggest ways to avoid confusion in future reports. COST TERMINOLOGY

A variety of terms used more or less interchangeably in health care financing studies of transplantation can have very different meanings. These include costs, expenditures, payments, reimbursements, and charges. Accounting Costs

In the health care field, costs for various services are usually measured in terms of accounting costs. Accounting costs per service can be thought of as a health care provider's average monetary outlay or expenditure for the production of a given type service. An organ transplantation or any of its component parts (eg, a hospital stay or an organ acquisition) is an example of a health care service. From the provider's perspective, accounting costs are computed using total direct and indirect (overhead) expenditures averaged across the number of services provided. Because accounting costs are average values for a particular type of service, they represent approximations of the economic costs incurred in the provision of that service. A common source of accounting cost data is the Health Care Financing Administrations's (HCFA) Medicare Cost Report. A potential underlying problem with accounting costs stems from the lack of uniformity among providers in defining cost centers and differences in computational methods used for indirect cost allocation. Methodologic inconsistencies may arise from provider differences in statistical bases used in allocating indirect costs and the step-down sequences used in assigning costs among indirect cost centers, such as housekeeping, maintenance, and dietary services. These factors may also change over time, making cost comparisons difficult and imprecise. The extent of these confounding factors is not known. However, reducing large categories of expenditures (such as accommodation, operating room, pharmacy, and laboratory) into average individual stay cost estimates is an inexact process at best. Hospital critics have claimed that "the method of allocating costs varies and may result in cross-subsidization among departments. As a result, departmental costs may be reflective of hospitals' attempts to maximize reimbursement rather than true estimates of costs of care provided in each department."31 Nevertheless, most analysts assessing hospital profitability typically use hospital cost report data. 26,32 A second problem with using accounting costs is that they result only in average costs per transplant. To the extent that one wants to associate patient characteristics or transplant outcomes with costs, accounting costs may not be specific enough. Payments and Reimbursements

In the past, third-party payers, such as Medicare or Blue Cross, provided payments to institutional providers based on average, or accounting, costs. Pay-

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ments or reimbursements, therefore, may be similar to provider costs; however, they may differ with the specific nature of the provider/payer agreement, as reflected in benefit coverage limitations or accounting methods. Viewed from the payer's perspective, the terms provider payments or reimbursements represent the payer's purchasing cost. Currently Medicare reimburses hospitals largely on the basis of Diagnosis Related Groups (DRGs). In general, DRGs are intended to approximate a hospital's average total cost associated with a given type of hospital stay. Additional pass-through payments are made to hospitals for direct medical education costs. In the caSe of organ transplantation, Medicare makes a further pass-through to cover the costs of organ acquisition. Both direct medical education and organ acquisition are reimbursed based on allowed costs. Organ acquisition is discussed in more detail in the next section. Negotiated payments to hospitals, such as those used by some health maintenance organizations, may be based on other criteria. For example, payments could be computed as a percentage of hospital charges or based on itemized costs of services such pharmacy, laboratory, and operating room comprising a hospital stay. These payments may be significantly different from Medicare payments for a given type of hospital stay.

Charges

Charges are dollar amounts billed by health care providers and therefore have the advantage of being specific to an individual procedure and relatively easy to obtain. The major problem with the use of charge data is that they may bear little relationship to costs and can vary greatly across hospitalsP "Charges are set by hospitals based on many factors including estimated costs, market conditions, payer mix, and revenue maximization strategies. This process may result in charges that are significantly above or below the costs of resources used to produce the service. The variation in charge-setting practices also results in charges that are generally not comparable across hospitals."32 Typically, hospital charges are set substantially above actual costs. In the case of Medicare, overall DRG payments to hospitals represent between 50% and 80% of hospital billed charges. Even under the old cost reimbursement system used prior to DRGs, the cost-to-charges ratio was about 65% to 70%. Despite these problems, charges may be related to costs in a proportional sense and are therefore useful in measuring relative resource consumption among transplantation procedures. Moreover, just as transplant outcomes are subject to improvements over time, the costs of transplant can also change. For example, reductions in posttransplant graft failure episodes and complications are likely to reduce hospital charges for the transplant stay itself. Sometimes efficiencies in hospital operations are responsible for reducing hospital charges. 34 Much of the literature citing transplantation costs does not explain the nature of the data being used. Thus, the organ transplantation literature is difficult to interpret with respect to cost measures. In some cases, charge data serve as the source of estimated costs, although a wide variety of terms is used to represent "costs." Although they bear some similarities in a general sense, they can vary considerably, and failure to specify the meaning of the terms can result in confusion. In addition, most of the studies include only the transplant hospital stay itself, omitting the pre- and post-transplant costs.

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COST-EFFECTIVENESS

Analyses of cost-effectiveness require that costs (or some surrogate measure) and outcome be measured for both the treatment under study and an alternative therapy.B, 9, 43 This has been available for kidney transplantation, for which the obvious alternative is dialysis.10, 11, 21, 37 Comparisons are not as clear for other solid organ transplants. No effective replacement mechanical heart, liver, or lung exists. For end-stage heart, liver, and lung disease, only medical management is available, with little hope of long-term survival. Still, a fair cost-effectiveness comparison would require that the costs of medical management, as well as patient survival, be collected for persons not receiving the transplant, probably from the time they are registered on a transplant waiting list. Another major analytic concern is control for patient severity. Without reasonable alternate therapies, randomizing patients into treatment protocols is not possible. Consequently, the next best alternative is an observational study with controls for patient severity or co-morbidity. This could be accomplished in part by limiting comparisons of transplant patients to other persons on waiting lists. However, more severely ill patients may not live long enough to receive a transplant and thus bias the comparison group outcomes downward (poorer survival) while biasing costs upward owing to the high costs associated with the terminal events.12 The problems in assessing cost-effectiveness in the transplantation literature have been summarized well by the Agency for Health Care Policy and Research in their assessment of liver transplantation, "To assess the costs and benefits of liver transplantation, it is important to compare the actual costs of transplantation . . . to the cost of supportive care if transplantation is not performed . . . cost data reported in the literature often do not include the same factors and some do not include all the relevant costs, which range from purchase of the donor organ and use of blood products to hospital costs, follow-up outpatient care, and drug costS."l ELEMENTS OF TRANSPLANT COSTS

Transplantation can be thought of as having three phases; (1) pre-transplantation, including registration, evaluation, and monitoring; (2) the transplant stay itself, including organ acquisition, the hospitalization, and physician fees; and (3) the post-transplant phase, including immunosuppressive therapy, rejection, and other complication episodes. Most assessments of transplant costs are limited to the transplant stay itself. Although this has a certain inherent logic to it, it can ignore Significant costs associated with the overall treatment. Patient registration and monitoring while awaiting transplant can add significant costs to transplantation. In fact, the Office of the Inspector General in the Department of Health and Human Services found that waiting list costs were one of the major costs associated with kidney transplantation.27 The rapid expansion of kidney transplant waiting lists in recent years has added greatly to these costs. 12,19 TRANSPLANT COSTS

Given the concerns listed above, the literature gives a wide array of information on various aspects of transplant costs and even some indications of cost-

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effectiveness. The most commonly reported cost-related data on organ transplantation are based on hospital charges. A number of analyses of kidney transplant hospital charges have been done. Shows tack et aP5 found that the introduction of CsA reduced nominal hospital charges at the University of California San Francisco transplant center by $15,000 between 1982 and 1987 (from $52,983 to $37,174). Evans et aP5 have a similar estimate for median charges for kidney transplants in 1988 of $39,625. HCFA data are consistent with these figures, showing median charges over the period 1984 to 1990 of $38,000 (unpublished HCFA data). Hospital transplant charges are sensitive to outcomes (Almond et aF estimate that delayed graft function can add $15,300 in charges to a stay), efficiencies (Johnson et aF2 estimate that hospital charges are $4000 less with pulsatile perfusion than with cold storage), and patient characteristics.33 A larger variation in hospital charge data is shown for other organ transplants. Staschak et a1/8 for example, show liver transplant charges at the University of Pittsburgh to have been $244,063 under a CsA regimen and $134,169 under an FK506 regimen. The $134,000 is more consistent with other reports. 13,21 However, as shown by Laudicina,25 some Medicaid agencies have negotiated rates as low as $73,713. Heart transplant stay charges are usually estimated to be in the range of $100,000,14 although once again Laudicina25 shows that some Medicaid agencies have negotiated significantly lower rates of about $47,000, Organ acquisition is often a difficult part of the transplant cost to assessy,28 For Medicare, organ acquisition is not included in the DRG payment but is included as a "pass-through" payment in which Medicare pays on the basis of allowed costs. The costs included in organ acquisition are much broader than direct payments to organ-procurement agencies (although these account for the largest share of costs). Also included are tissue typing, donor and recipient evaluation, donor general routine and special care services, operating room and other inpatient ancillary services applicable to the donor, preservation and perfusion costs, registration of recipient with a transplant registry, surgeons' fees for excising cadaver kidneys, transportation, and all pre-admission physician services, such as laboratory, electroencephalography, and surgeon fees for cadaver excisions, The Office of the Inspector General estimated that in 1985, more than 40% of the cost of kidney transplantation was due to organ acquisition and that about 20% of the costs of organ acquisition were due to pre-transplant laboratory costS.'8 Owing to the large increases in numbers of persons on waiting lists for kidney transplantation, these costs have continued to rise. Between 1985 and 1991 the number of Medicare-covered kidney transplants increased by about 29%-from 7100 to 9200, However, Medicare payments for kidney acquisition doubled from $100 million to $200 million (unpublished Medicare cost report data), As a result, the average cost (to Medicare) for kidney acquisition has risen to more than $20,000 per kidney, An indication of the potential for increased efficiencies in organ acquisition was shown by Orlowski et aV9 who demonstrated a $3500 savings per transplant by switching from chartered flights to commercial carriers for transporting cadaver kidneys. Payments to surgeons and physicians overseeing transplantation and posttransplant graft function are generally not reported in the literature on transplantation, A full accounting of the costs of transplantation, however, needs to include these significant payments. As noted above, in Medicare's payment system, physician services related to organ acquisition are included in organ acquisition pass-through payments to the hospitaL The obvious fees to include are the transplant surgeons' fees, which can be considerable, In 1992, the average Medicare allowed surgeons' charges for kidney, heart, and liver transplant were $1942, $5451, and $6662, respectively, Other physician services that need to be counted

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include assistance at surgery, anesthesiology, and additional physician services provided during the transplant stay. All physician services provided during the post-transplant period should also be included. Reports on post-transplant costs are usually restricted to immunosuppression. The concern with immunosuppression costs is probably related to its high cost and the lack of insurance coverage for these drugs. Although initial estimates of the annual cost of CsA for kidney transplants were in the range of $8000, experience in reducing dosage levels in combination with other pharmaceutical agents has reduced the annual cost to $4000 to $5000.'5,39 However, Barclay et al5 found considerable variation in immunosuppression therapy costs, ranging from $4881 for conversion therapy to more than $10,000 for quadruple therapy. Showstack et aP6 found that, although CsA reduced resource consumption during the transplant stay itself, it had no impact on long-term hospital costs. Estimates of costs of immunosuppression for heart transplants are usually higher. Valantine et al42 estimate costs of more than $12,000 for 2 to 4 months of therapy without diltiazem and more than $6000 with diltiazem. On the other hand, estimates of the annual costs of CsA are about $6800 for heart transplant recipients. Ketoconozole has been reported to reduce this amount by as much as $1800. 6,16,18 The cost impact of other immunosuppressive agents is unclear. Johnson et aP3 found that antilymphocyte globulin had no clinical benefit in kidney transplants with immediate function but added $3000 to the costs. On the other hand, as noted above, Staschak reported a $100,000 cost savings in initial liver transplant hospitalization of FK506 compared with CsA, an effect unlikely to be repeated at other centers. Other post-transplant interventions can also impact costs. Appleton et aP have reported savings of $1000 in post-heart transplant endomyocardial biopsies with echocardiography as opposed to fluoroscopically guided biopsies. Clark et aF have reported savings of £1260 using flow-cytometric monitoring of anti thymocyte globulin therapy for steroid-resistant rejection. Overall costs of transplantation, including pre- and post-transplant time periods, have generally not been assessed. The exception is kidney transplant, for which Medicare data are available. These data include all Medicare payments for all hospitalizations, organ acquisition, physician care, and dialysis. Recent Medicare data show that Medicare payments for the first year following kidney transplantation have risen from $54,000 in 1986 to $80,000 in 1991, with most of the increase coming in the area of hospitalization (which includes organ acquisition).20 Post-first-year costs to Medicare have remained fairly constant at about $7000 during this time (not including immunosuppression). During this same period, annual per capita dialysis expenditures (again including hospitalization, physician services, and dialysis) increased from $36,000 to $39,000. In terms of overall cost-effectiveness, kidney transplant has been shown to be consistently superior to dialysis, in terms of both Medicare expenditures and total estimated costs,10, 11, 20 Similar results have been found in other countries!,24 In the nonrenal area at least one attempt has been made to compare the charges for transplanted patients with charges for comparable nontransplanted patients. Pageaux et al30 found that the average hospital cost of liver transplantation for alcoholic cirrhosis, including the transplant itself and the first year of follow-up, was $86,000. Liver transplantation for liver disease not resulting from alcoholism was $63,000. The hospital cost associated with medical management of alcoholic cirrhosis in the last year of life was $31,000 (Williams et al45 estimate the total last-year-of-life costs associated with terminal liver disease to be more than $47,000), In terms of benefits, the transplantation group is clearly superior

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because the comparison group (because of the way it was selected) had 100% mortality. CONCLUSIONS

The progress of solid organ transplantation has been tracked for a number of years. The HCFA has published data on kidney transplants since 1978, and the United States Renal Data System has published data on kidney transplants since 1989. The UCLA Kidney Transplant Registry precedes these efforts. More recently, UNOS has published information on the other solid organ transplantsheart, liver, lung, and pancreas. For the most part, these data sources deal only with the clinical and epidemiologic side of transplantation. Although most researchers acknowledge the high cost of transplantation, very little has been done in the way of systematic analyses of the nature of these costs. Future analyses of organ transplantation could be greatly improved in a few areas. First, to the extent possible, studies of organ transplantation costs should include all the costs associated with the medical care of the transplant patient. These include such things as registration on waiting lists, costs associated with maintaining candidacy on the waiting list, organ acquisition, the transplant hospital stay itself, follow-up hospitalizations and immunization costs, and all physician costs incurred at the time of transplantation and during the pre- and posttransplant phases as well. Probably not much is to be gained by trying to determine a priori what medical events (and associated costs) should count as a transplant-related event. It is better to collect all the medical costs for patients under study. It is always possible to reanalyze the data at a later time to differentiate between transplant-related and transplant-unrelated events. Second, the costs should be derived, as much as possible, from the same source(s). Many of the differences in the literature on transplant costs can be attributed to variations in how hospitals set charge levels for transplantation. For example, combining charge data (from hospitals) with estimated payments based on patient recollection or on average protocols (immunosuppression) adds a great deal of imprecision to the overall cost estimates. Funding sources such as Medicare or other large insurers have the advantage of having relatively consistent information on their payments. Medicare has been an excellent source of cost data on kidney transplants for a number of years. More recently, Medicare's coverage of heart transplants (October 1986) and liver transplants (March 1990) opens the possibility of similar cost studies for these transplants. Third, much more attention needs to be paid (particularly for nonrenal transplants) to comparison with patients not receiving the transplant. The fact that a heart transplant may cost $150,000 for the first year of treatment is not, in and of itself, terribly informative. Just as the survival rate with transplant is insufficient without knowing the survival rate without transplant, the costs are also insufficient without knowing the alternative costs. UNOS maintains a longitudinal census of all patients registered on the waiting list for each of the types of transplantation. Just as this is the basic national source of information used to assess the clinical effectiveness of transplantation, it could also be used as the basis for selecting patients for studies comparing costs of transplantation with the costs of medical management. References 1. Agency for Health Care Policy and Research: Assessment of Liver Transplantation:

Health Technology Assessment Reports. DHHS Publication No. (PHS) 90-3455, 1990

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2. Almond PS, Troppmann C, Escobar F, et al: Economic impact of delayed graft function. Transplant Proc 23:1034,1991 3. Appleton RS, Miller LW, Nouri S, et al: Endomyocardial biopsies in pediatric patients with no irradiation: Use of internal jugular venous approach and echocardiographic guidance. Transplantation 51:309-311, 1991 4. Aranzabal I, Perdigo L, Mijares J, et al: Renal transplantation costs: An economic analysis and comparison with dialysis costs. Transplant Proc 23:2574, 1991 5. Barclay PG, Allen RD, Stewart JH, et al: Costs of immunosuppressive therapies used in renal transplantation. Transplant Proc 24:165-166, 1992 6. Butman SM, Wild JC, Nolan PE, et al: Prospective study of the safety and financial benefit of ketoconazole as adjunctive therapy to cyclosporine after heart transplantation. J Heart Lung Transplant 10:351-358, 1991 7. Clark KR, Forsythe JL, Shenton BK, et al: Flow-cytometric monitoring of ATG therapy for steroid-resistant rejection. Transplant Proc 24:315,1992 8. Detsky AS, Naglie IG: A clinician's guide to cost-effectiveness analysis. Ann Intern Med 113:147-154,1990 9. Doubilet P, Weinstein MC, McNeil BJ: Use and misuse of the term "cost effective" in medicine. N Engl J Med 314:253-256,1986 10. Eggers PW: Analyzing the cost-effectiveness of kidney transplantation. Proceedings of the 19th National Meeting of the Public Health Conference on Records and Statistics. DHHS Publication No. (PHS) 84-1214, 1984 11. Eggers PW: Comparison of treatment costs between dialysis and transplantation. Semin NephroI12:284-289, 1992 12. Evans RW: Organ procurement expenditures and the role of financial incentives. JAMA 269:3113-3118, 1993 13. Evans RW, Manninen DL, Dong FB: The National Cooperative Transplantation Studyfinal report. Seattle, WA, Battelle Human Affairs Research Centers, 1991 14. Evans RW, Manninen DL, Overcast TD: The National Heart Transplantation Studyfinal report. Seattle, WA, Battelle Human Affairs Research Centers, 1984 15. Evans RW, Manninen DL, Thompson C: A cost and outcome analysis of kidney transplantation: The implications of initial immunosuppressive protocol and diabetes. Final Report, HCFA, August, 1989 16. First MR, Schroeder TI, Weiskittel P, et al: Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients. Lancet 2:1198-1201,1989 17. Gorman KJ, Fein AI, Shield CF: Relationship between clinical outcome, inpatient length of stay, and cost of renal transplantation at four US transplant centers. Transplant Proc 25:1690-1691,1993 18. Gueco IP, Tan-Torres T, Baniga U, et al: Ketoconazole in post transplant triple therapy: Comparison of costs and outcomes. Transplant Proc 24:1709-1714, 1992 19. Health Care Financing Administration: End-Stage Renal Disease Research Report, 1991. HCFA Publication No. 03338, 1993 20. Held PI, Turenne MN, Bovbjerg RR, et al: Cost-effectiveness of ESRD treatment modalities. Final Report, HCFA, April, 1992 21. Henderson JM, Gilmore GT, Hooks MA, et al: Selective shunt in the management of variceal bleeding in the era of liver transplantation. Ann Surg 216:248-254,1992 22. Johnson CP, Roza AM, Adams MB: Local procurement with pulsatile perfuSion gives excellent results and minimizes initial cost associated with renal transplantation. Transplant Proc 22:385-387, 1990 23. Johnson CP, Slakey DP, Callaluce RD, et al: Prospective randomized comparison of quadruple vs triple therapy for first cadaver transplants with immediate function. Transplant Proc 25:585-586,1993 24. Karlberg I: Cost analysis of alternative treatments in end-stage renal disease. Transplant Proc 24:335,1992 25. Laudicina S: Medicaid coverage and payment policies for organ transplants: Findings of a national survey: Prepared for the Health Resources and Services Administration, USDHHS. November, 1988 26. Newhouse JP: Do unprofitable patients face access problems? Health Care Financing Review 11:33-42, 1989 27. Office of the Inspector General: Addressing increased organ acquisition costs: A management advisory report. Publication No. OEI-01-88-01331, 1991

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28. Office of the Inspector General: Organ acquisition costs: An overview. Publication No. OAI-OI-86-00108,1987 29. Orlowski JP, Jaynes CL, Spees EK: Practical reduction of transplantation costs: Use of commercial transportation instead of charter aircraft for sharing pancreas grafts. Arch Surg 128:1111-1114, 1993 30. Pageaux GP, Souche B, Pemey P, et al: Results and cost of orthotopic liver transplantation for alcoholic cirrhosis. Transplant Proc 25:1135-1136, 1993 31. Price KF: Pricing Medicare's diagnosis-related groups: Charges versus estimated costs. Health Care Financing Review 11:79-90, 1989 32. Prospective Payment Assessment Commission: Technical appendix to the report and recommendations to the Secretary, USDHHS. March 1, 1988 33. Reemtsma K, Berland G, Merrill J, et al: Evaluation of surgical procedures: Changing patterns of patient selection and costs in heart transplantation. J Thorac Cardiovasc Surg 104:1308-1311, 1992 34. Saywell RM, Woods JR, Halbrook HG, et al: Cost analysis of heart transplantation from the day of operation to the day of discharge. J Heart Transplant 8:244-252,1989 35. Showstack J, Katz P, Amend W, et al: The effect of cyc1osporine on the use of hospital resources for kidney transplantation. N Engl J Med 321:1086-1092,1989 36. Showstack J, Katz P, Amend W, et al: The association of cyc1osporine with the I-year costs of cadaver-donor kidney transplants. JAMA 264:1818-1823,1990 37. Stange PV, Sumner AT: Predicting treatment costs and life expectancy for end-stage renal disease. N Engl J Med 298:372-378,1978 38. Staschak 5, Wagner 5, Block G, et al: A cost comparison of liver transplantation with FK 506 or CyA as the primary immunosuppressive agent. Transplant Proc 22:47-49, 1990 39. Thistlethwaite JR, Haag BW, Jones KW, et al: Elective conversion from cyc1osporine to azathioprine in recipients with stable renal function 6 months after kidney transplantation. Hum ImmunoI14:314-323, 1985 40. United Network for Organ Sharing and the Division of Organ Transplantation, Bureau of Health Resources Development, USDHHS: 1993 Annual Report of the US Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network-transplant data: 1988-1991 41. US General Accounting Office: Heart transplants: Concerns about cost, access, and availability of donor organs. GAO Report No. GAO/HRD-89-61, 1989 42. Valantine H, Keogh A, McIntosh N, et al: Cost containment: Coadministration of diltiazem with cyc1osporine after heart transplantation: J Heart Lung Transplant 11:17,1992 43. Weinstein MC, Stason WB: Foundation of cost-effectiveness analysis for health and medical practices. N Engl J Med 296:716-721, 1977 44. Welch HG, Larson EB: Dealing with limited resources: The Oregon decision to curtail funding for organ transplantation. N Engl J Med 319:171-173,1988 45. Williams JW, Vera 5, Evans LS: Socioeconomic aspects of hepatic transplantation. Am J GastroenteroI82:1115-1119,1987

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