Zoltán Kaló

The expanded criteria donor dilemma in cadaveric renal transplantation

Background. Outcomes of expanded criteria donor (ECD) kidney transplants are known to be superior to dialysis but inferior to transplant with a standard donor. Because of recent policy changes, ECD kidneys will be offered only to patients who have agreed to consider such an organ in advance. There is wide variation in opinion concerning the composition of ECD wait lists. However, the relative benefits of accepting an ECD versus waiting for a standard donor have not been quantified. Methods. A Markov model was developed to determine when an individual patient should accept or reject an offer of an ECD kidney to optimize their personal expected quality-adjusted life years (QALY). Input variables were estimated from the United States Renal Data System (USRDS) database using a sample of 35,030 recipients. Results. Recipients of ECD kidneys waited 77 days longer for transplant than recipients of standard donors. The average patient could wait 3.2 years longer, in addition to the time they have already waited, for a standard donor than an ECD and expect equivalent QALYs. Selected subsets revealed differences in wait times that equated QALYs for ECD and standard donors: African American, 4.4 years; age under 30, 4.0 years; age over 60, 11 months. Conclusions. Existing policy is likely to be in the best interests of only certain sets of patients awaiting cadaveric kidney transplantation unless ECDs dramatically reduce expected waiting for transplantation. This is most possible in elderly patients because of the short wait-time reduction required to make ECDs beneficial. Data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. The data and analyses reported in the 2001 Annual Report of the United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients have been supplied by the United Network for Organ Sharing and University Renal Research and Education Association under contract with Health and Human Services. The authors alone are responsible for reporting and interpreting of these data.

Cost-Effectiveness of Organ Donation: Evaluating Investment into Donor Action and Other Donor Initiatives

Initiatives aimed at increasing organ donation can be considered health care interventions, and will compete with other health care interventions for limited resources. We have developed a model capable of calculating the cost‐utility of organ donor initiatives and applied it to Donor Action, a successful international program designed to optimize donor practices.

The Life-Years Saved by a Deceased Organ Donor

Understanding the additional life‐years given to patients by deceased organ donors is necessary as substantial investments are being proposed to increase organ donation. Data were drawn from the Scientific Registry of Transplant Recipients. All patients placed on the wait‐list as eligible to receive or receiving a deceased donor solid organ transplant between 1995 and 2002 were studied. The benefit of transplant was determined by the difference in the expected survival experiences of transplant recipients and candidates expecting transplant soon. An average organ donor provides 30.8 additional life‐years distributed over an average 2.9 different solid organ transplant recipients, whereas utilization of all solid organs from a single donor provides 55.8 additional life‐years spread over six organ transplant recipients. The relative contribution of the different organs to the overall life‐year benefit is higher for liver, heart and kidney, and lowest for lung and pancreas. The life‐year losses from unprocured and unused organs are comparable to suicide, congenital anomalies, homicide or perinatal conditions and half that of HIV. Approximately 250 000 additional life‐years could be saved annually if consent for potential deceased donors could be increased to 100%. Therefore, increasing organ donation should be considered among our most important public health concerns.

Multiple Criteria Decision Analysis for Health Care Decision Making—Emerging Good Practices: Report 2 of the ISPOR MCDA Emerging Good Practices Task Force

Health care decisions are complex and involve confronting trade-offs between multiple, often conflicting objectives. Using structured, explicit approaches to decisions involving multiple criteria can improve the quality of decision making. A set of techniques, known under the collective heading, multiple criteria decision analysis (MCDA), are useful for this purpose. In 2014, ISPOR established an Emerging Good Practices Task Force. The task forces first report defined MCDA, provided examples of its use in health care, described the key steps, and provided an overview of the principal methods of MCDA. This second task force report provides emerging good-practice guidance on the implementation of MCDA to support health care decisions. The report includes: a checklist to support the design, implementation and review of an MCDA; guidance to support the implementation of the checklist; the order in which the steps should be implemented; illustrates how to incorporate budget constraints into an MCDA; provides an overview of the skills and resources, including available software, required to implement MCDA; and future research directions.

The cost effectiveness of Apligraf® treatment of diabetic foot ulcers

AbstractBackground: Diabetic foot ulcers (DFUs) present a treatment challenge and result in a large economic burden, requiring careful evaluation of the clinical efficacy and cost effectiveness of new treatment modalities. DFU clinical trials of the bio-engineered skin substitute Apligraf® (Novartis Pharma AG, Basel, Switzerland) have demonstrated improved clinical efficacy compared with good wound care (GWC) alone. Objective: To determine the economic impact and cost effectiveness of Apligraf® plus GWC compared with GWC alone in the treatment of DFUs. Study perspective: Societal. Methods: A Markov-based simulation model was created to compare the costs and effects of Apligraf® plus GWC to those of GWC alone over a 12-month period. The primary health states were ‘uninfected ulcer’, ‘infected ulcer’, ‘gangrene’, and ‘healed ulcer’. Transition probabilities were based on clinical trial results, while cost estimates were based on estimates of resource utilisation in the Netherlands. The cost-effectiveness outcome measures were the incremental cost per ulcer-free month gained and the incremental cost per amputation avoided. Results: Costs in the first year of treatment were €4656 for Apligraf® plus GWC and €5310 for GWC alone (1999 values). Treatment with Apligraf® led to lower costs since its greater effectiveness offset the added cost of the product. This benefit was realised after 5 months, the crossover point of the two cost curves. Apligraf® use increased the amount of ulcer-free time by by 1.53 months (7.78 vs 6.25) and reduced the risk of amputation (6.3% vs 17.1%). Sensitivity analyses showed that cost parameters (e.g. units of Apligraf® required, cost of treatment practice) and transition probabilities between health states affected the cost results. Conclusions: Treatment with Apligraf® plus GWC resulted in a 12% reduction in costs over the first year of treatment compared with GWC alone. The increased ulcer-free time coupled with a reduced risk of amputation to a large extent offset the initial costs of the product.

Resource use and treatment costs after kidney transplantation: Impact of demographic factors, comorbidities, and complications

Background. Our goal was to quantify outcomes, resource use, and treatment costs for the first 2 years after renal transplantation in a “real-life” European setting and to assess the impact of preoperative risk factors and postoperative complications on treatment costs. Methods. Inpatient and outpatient records of all patients who received a renal transplant at Medizinische Hochschule Hannover, Germany, between January 1998 and July 2000, were evaluated. Key clinical events were recorded. Direct costs were calculated for primary hospitalization, the remainder of year 1, and year 2 after transplantation. Cost of organ procurement, pretransplant care, and transplant surgery were excluded. Cost consequences for key clinical events were determined. Results. Of 204 patients undergoing transplantation, 195 and 149 completed 1 year and 2 years of follow-up, respectively. The outcomes of years 1 and 2, respectively, were as follows: graft failure, 5.4%, 0.7%; acute rejection, 35.9%, 5.4%; cytomegalovirus (CMV) infection, 29.2%, 2.0%; and delayed graft function, 30.9%. Costs for primary hospitalization, the remainder of year 1, and year 2 averaged &U20AC;15,380, &U20AC;18,636, and &U20AC;14,484, respectively. Cost-driving events included graft failure &U20AC;36,228), acute rejection (&U20AC;9,638), delayed graft function (&U20AC;7,359), and CMV infection (&U20AC;4,149). Graft failure and acute rejection for year 1 also added significantly to the costs for year 2. Conclusions. These results show that posttransplant clinical outcomes result in a significant increase in treatment costs. Because the economic impact of primary causes of chronic rejection (acute rejection and CMV) and delayed graft function is substantial, careful selection of the most appropriate immunosuppressive regimen is essential.

Meta-Analysis of Basiliximab for Immunoprophylaxis in Renal Transplantation

BackgroundBasiliximab is a high-affinity chimeric monoclonal antibody directed against the α-chain of the interleukin (IL)-2 receptor. Individual studies have shown that it is highly effective in preventing acute rejection and causes no measurable incremental toxicity. However, incorporation of basiliximab immunoprophylaxis into routine practice depends upon the demonstration of benefit across treatment regimens and quantitation of the treatment effect.MethodsThis study employed a meta-analysis to examine the clinical benefit of basiliximab. Parameter estimates were derived from four randomised prospective double-blind studies conducted in 93 renal transplant centres in 18 countries. A total of 1185 adult primary allograft recipients were randomised within the centres to receive either basiliximab 20mg intravenously on days 0 and 4 or placebo, in addition to double or triple immunosuppression consisting of cyclosporin-microemulsion (Neoral®1), corticosteroids, and azathioprine or mycophenolate mofetil. Key clinical events included patient and graft survival, graft rejection and complications. Analysis was performed using a variable model; odds ratios and the numbers needed to treat (NNT) to benefit or to harm one patient were calculated for each principal outcome at 6 or 12 months post-transplant.ResultsBasiliximab reduced the relative risk (RR) and absolute risk (AR) of clinical and biopsy-proven acute graft rejection across all treatment regimens. The overall RR of clinical acute graft rejection was decreased by 35% in patients receiving basiliximab. AR was reduced by 15.6% (pooled incidence: 28.8% vs 44.4%, p < 0.0001), and the NNT for efficacy was six. The reduction in RR of biopsy-proven rejection was similar (32%) with an absolute risk reduction (ARR) of 11.7% (pooled incidence: 25.1% vs 36.8%, p < 0.0001) and NNT of nine over 6 months. There was a concomitant reduction in the risk of graft loss which did not reach statistical significance (p = 0.14). The RR of graft loss was reduced by 26% with an AR reduction of 2.3% (pooled incidence: 6.4% vs 8.7%) and an NNT of 42 over 6 months. The risk of death was unchanged.ConclusionsImmunoprophylaxis with basiliximab produces a significant reduction in the RR and AR of clinical and biopsy-proven acute graft rejection with a trend towards a concomitant reduction in the risk of graft loss. The magnitude of protection provided by basiliximab, the fact that it is observed across treatment regimens and the safety of this therapy are arguments for its routine use in renal transplantation.

Capacity Building for HTA Implementation in Middle-Income Countries: The Case of Hungary

OBJECTIVES Middle-income countries often have no clear roadmap for implementation of health technology assessment (HTA) in policy decisions. Examples from high-income countries may not be relevant, as lower income countries cannot allocate so much financial and human resources for substantiating policy decisions with evidence. Therefore, HTA implementation roadmaps from other smaller-size, lower-income countries can be more relevant examples for countries with similar cultural environment and economic status. METHODS We reviewed the capacity building process for HTA implementation in Hungary with special focus on the role of ISPOR Hungary Chapter. RESULTS HTA implementation in Hungary started with capacity building at universities with the support of the World Bank in the mid 90s, followed by the publication of methodological guidelines for conducting health economic evaluations in 2002. The Hungarian Health Economics Association (META) - established in 2003 - has been recognized as a driving force of HTA implementation. META became the official regional ISPOR Chapter of Hungary in 2007. In 2004 the National Health Insurance Fund Administration made the cost-effectiveness and budget impact criteria compulsory prior to granting reimbursement to new pharmaceuticals. An Office of Health Technology Assessment was established for the critical appraisal of economic evaluations submitted by pharmaceutical manufacturers. In 2010 multicriteria decision analysis was introduced for new hospital technologies. CONCLUSION The economic crisis may create an opportunity to further strengthen the evidence base of health care decision-making in Hungary. In the forthcoming period ISPOR Hungary Chapter may play an even more crucial role in improving the standards of HTA implementation and facilitating international collaboration with other CEE countries.

Differential pricing of new pharmaceuticals in lower income European countries

Pharmaceutical companies adjust the pricing strategy of innovative medicines to the imperatives of their major markets. The ability of payers to influence the ex-factory price of new drugs depends on country population size and income per capita, among other factors. Differential pricing based on Ramsey principles is a ‘second-best’ solution to correct the imperfections of the global market for innovative pharmaceuticals, and it is also consistent with standard norms of equity. This analysis summarizes the boundaries of differential pharmaceutical pricing for policymakers, payers and other stakeholders in lower-income countries, with special focus on Central-Eastern Europe, and describes the feasibility and implications of potential solutions to ensure lower pharmaceutical prices as compared to higher-income countries. European stakeholders, especially in Central-Eastern Europe and at the EU level, should understand the implications of increased transparency of pricing and should develop solutions to prevent the limited accessibility of new medicines in lower-income countries.

HTA Implementation Roadmap in Central and Eastern European Countries

Abstract The opportunity cost of inappropriate health policy decisions is greater in Central and Eastern European (CEE) compared with Western European (WE) countries because of poorer population health and more limited healthcare resources. Application of health technology assessment (HTA) prior to healthcare financing decisions can improve the allocative efficiency of scarce resources. However, few CEE countries have a clear roadmap for HTA implementation. Examples from high‐income countries may not be directly relevant, as CEE countries cannot allocate so much financial and human resources for substantiating policy decisions with evidence. Our objective was to describe the main HTA implementation scenarios in CEE countries and summarize the most important questions related to capacity building, financing HTA research, process and organizational structure for HTA, standardization of HTA methodology, use of local data, scope of mandatory HTA, decision criteria, and international collaboration in HTA. Although HTA implementation strategies from the region can be relevant examples for other CEE countries with similar cultural environment and economic status, HTA roadmaps are not still fully transferable without taking into account country‐specific aspects, such as country size, gross domestic product per capita, major social values, public health priorities, and fragmentation of healthcare financing. Copyright