Health technology assessment in Switzerland: a descriptive analysis of "Coverage with Evidence Development" decisions from 1996 to 2013.

OBJECTIVES: To identify factors associated with the decisions of the Federal Department of Home Affairs concerning coverage with evidence development (CED) for contested novel medical technologies in Switzerland. DESIGN: Quantitative, retrospective, descriptive analysis of publicly available material and prospective, structured, qualitative interviews with key stakeholders. SETTING: All 152 controversial medical services decided on by the Federal Commission on Health Insurance Benefits within the framework of the new federal law on health insurance in Switzerland from 1997 to 2013, with focus on 33 technologies assigned initially to CED and 33 to evidence development without coverage. MAIN OUTCOME MEASURES: Factors associated with numbers and type of contested services assigned to CED per year, the duration and final outcome of the evaluations and perceptions of key stakeholders. RESULTS: The rate of CED decisions (82 total; median 1.5/year; range 0-9/year), the time to final decision (4.5 years median; 0.75 to +11 years) and the probability of a final 'yes' varied over time. In logistic regression models, the change of office of the commission provided the best explanation for the observed outcomes. Good intentions but absence of scientific criteria for decisions were reported as major comments by the stakeholders. CONCLUSIONS: The introduction of CED enabled access to some promising technologies early in their life cycle, and might have triggered establishment of registries and research. Impact on patients' outcome and costs remain unknown. The primary association of institutional changes with measured end points illustrates the need for evaluation of the current health technology assessment (HTA) system.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Development of coverage with evidence development for medical technologies in Switzerland from 1996 to 2012.

OBJECTIVES: The aim of this study was to assess incidence, time frame, and outcome of "Coverage with Evidence Development" (CED) decisions in the Swiss Basic Health Insurance scheme. METHODS: Analysis of all controversial medical technologies submitted to review by the Swiss Federal Office of Public Health (FOPH) from 1996 to 2012 with focus on decisions with constraints. Description of types of technology, type of initial decision, duration of evaluation period, final decision, and search for potential factors associated with changes over time. RESULTS: Forty-five (37.5 percent) of 120 controversial health technologies were classified as "yes, in evaluation, reimbursed" for a certain period of time and thirty-five (29.2 percent) as "no, in evaluation, not reimbursed" by the Federal Department of Home Affairs from 1996 to 2012. The rate of CED decisions ranged between zero and nine per year and was influenced by type of technology and calendar year. Forty-four of forty-five decisions were subject to further restrictions, to a "center or a specialist" (76 percent), "indications" (49 percent), "registry" (31 percent), or "other" (49 percent). The time to a final decision ranged from 1.5 to 11 years (median, 6 years). No factors associated with initial decision and final outcome could be identified. CONCLUSIONS: CED as a reality in Switzerland might have enabled patients to obtain access to promising technologies early in their life cycle. CED might have acted as a trigger to a successful implementation of a comprehensive national registry. The lack of qualitative data stresses the urgent need for evaluation of the HTA decisions and their impact on patient outcome and costs.

Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study.

Fifty-five years after publication of the first hematopoietic stem cell transplantation this technique has become an accepted treatment option for defined hematologic and non-hematologic disorders. There is considerable interest in understanding differences in its use and trends on a global level and the macro-economic factors associated with these differences. Data on the numbers of hematopoietic stem cell transplants performed in the 3-year period 2006-2008 were obtained from Worldwide Network for Blood and Marrow Transplantation member registries and from transplant centers in countries without registries. Population and macro-economic data were collected from the World Bank and from the International Monetary Fund. Transplant rates were analyzed by indication, donor type, country, and World Health Organization regional offices areas and related to selected health care indicators using single and multiple linear regression analyses. Data from a total of 146,808 patients were reported by 1,411 teams from 72 countries over five continents. The annual number of transplants increased worldwide with the highest relative increase in the Asia Pacific region. Transplant rates increased preferentially in high income countries (P=0.02), not in low or medium income countries. Allogeneic transplants increased for myelodysplasia, chronic lymphocytic leukemia, acute leukemias, and non-malignant diseases but decreased for chronic myelogenous leukemia. Autologous transplants increased for autoimmune and lymphoproliferative diseases but decreased for leukemias and solid tumors. Transplant rates (P<0.01), donor type (P<0.01) aand disease indications (P<0.01) differed significantly between countries and regions. Transplant rates were associated with Gross National Income/capita (P<0.01) but showed a wide variation of explanatory content by donor type, disease indication and World Health Organization region. Hematopoietic stem cell transplantation activity is increasing worldwide. The preferential increase in high income countries, the widening gap between low and high income countries and the significant regional differences suggest that different strategies are required in individual countries to foster hematopoietic stem cell transplantation as an efficient and cost-effective treatment modality.

Hematopoietic stem cell transplantation in Europe. Differences between Eastern and Western countries.

Hemopoietic stem cell transplantation (HSCT) is increasingly used worldwide. The geographical distribution of this procedure is not homogenous within a particular continent. We have previously reviewed these differences in the use of bone marrow transplant in Europe, and in two reports we emphasized the economical reasons explaining these differences. The increasing demand for this high cost procedure represents a challenge for health care institutions. While patients need an optimal therapy, public health is confronted with limited resources. Information on changes in HSCT technology and on factors associated with its utilization might be of help. Insights into mechanisms of HSCT use are essential for rational decision making.

Changes in the use of hematopoietic stem cell transplantation: a model for diffusion of medical technology.

BACKGROUND: Innovations in hematology spread rapidly. Factors affecting the speed of introduction, international diffusion, and durability of use of innovations are, however, poorly understood. DESIGN AND METHODS: We used data on 251,106 hematopoietic stem cell transplants from 591 teams in 36 European countries to analyze the increase and decrease in such transplants for breast cancer and chronic myeloid leukemia and the replacement of bone marrow by peripheral blood as the source of stem cells as processes of diffusion. Regression analyses were used to measure the quantitative impact of defined macro- and microeconomic factors, to look for significant associations (t-test), and to describe the coefficient of determination or explanatory content (R(2)). RESULTS: Gross national income per capita, World Bank category, team density, team distribution, team size, team experience and, team innovator status were all significantly associated with some or all of the changes. The analyses revealed different patterns of associations and a wide range of explanatory content. Macro- and micro-economic factors were sufficient to explain the increase of allogeneic hematopoietic stem cell transplants in general (R(2) = 78.41%) and for chronic myeloid leukemia in particular (R(2) = 79.39%). They were insufficient to explain the changes in stem cell source (R(2) =26.79% autologous hematopoietic stem cell transplants; R(2) = 9.67% allogeneic hematopoietic stem cell transplants) or the decreases in hematopoietic stem cell transplants (R(2) =10.22% breast cancer; R(2)=33.17% chronic myeloid leukemia). CONCLUSIONS: The diffusion of hematopoietic stem cell transplants is more complex than previously thought. Availability of resources, evidence, external regulations and, expectations were identified as key determinants. These data might serve as a model for diffusion of medical technology in general.

Hematopoietic stem cell transplantation: a global perspective.

CONTEXT: Hematopoietic stem cell transplantation (HSCT) requires significant infrastructure. Little is known about HSCT use and the factors associated with it on a global level. OBJECTIVES: To determine current use of HSCT to assess differences in its application and to explore associations of macroeconomic factors with transplant rates on a global level. DESIGN, SETTING, AND PATIENTS: Retrospective survey study of patients receiving allogeneic and autologous HSCTs for 2006 collected by 1327 centers in 71 participating countries of the Worldwide Network for Blood and Marrow Transplantation. The regional areas used herein are (1) the Americas (the corresponding World Health Organization regions are North and South America); (2) Asia (Southeast Asia and the Western Pacific Region, which includes Australia and New Zealand); (3) Europe (includes Turkey and Israel); and (4) the Eastern Mediterranean and Africa. MAIN OUTCOME MEASURES: Transplant rates (number of HSCTs per 10 million inhabitants) by indication, donor type, and country; description of main differences in HSCT use; and macroeconomic factors of reporting countries associated with HSCT rates. RESULTS: There were 50 417 first HSCTs; 21 516 allogeneic (43%) and 28 901 autologous (57%). The median HSCT rates varied between regions and countries from 48.5 (range, 2.5-505.4) in the Americas, 184 (range, 0.6-488.5) in Asia, 268.9 (range, 5.7-792.1) in Europe, and 47.7 (range, 2.8-95.3) in the Eastern Mediterranean and Africa. No HSCTs were performed in countries with less than 300,000 inhabitants, smaller than 960 km(2), or having less than US $680 gross national income per capita. Use of allogeneic or autologous HSCT, unrelated or family donors for allogeneic HSCT, and proportions of disease indications varied significantly between countries and regions. In linear regression analyses, government health care expenditures (r(2) = 77.33), HSCT team density (indicates the number of transplant teams per 1 million inhabitants; r(2) = 76.28), human development index (r(2) = 74.36), and gross national income per capita (r(2) = 74.04) showed the highest associations with HSCT rates. CONCLUSION: Hematopoietic stem cell transplantation is used for a broad spectrum of indications worldwide, but most frequently in countries with higher gross national incomes, higher governmental health care expenditures, and higher team densities.

Predictability of hematopoietic stem cell transplantation rates.

BACKGROUND AND OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) is a complex and expensive procedure. Trends in the use of this procedure have appeared erratic in the past. Information on future needs is essential for health care administrators. DESIGN AND METHODS: We analyzed the evolution of transplant rates, e.g. numbers of transplants per 10 million inhabitants, in Europe from 1990 to 2004 for all major disease categories and used Gross National Income (GNI) per capita, team density (numbers of teams per 10 million inhabitants) and team distribution (numbers of teams per 10,000 km2) to measure the impact of economic factors in participating countries. Trends were compared by regression analyses, and countries were grouped by World Bank definitions into high, middle and low income categories. RESULTS: Transplant rates increased over time with nearly linear trends, in clear association with GNI per capita (R2=0.72), and distinct by World Bank category within a narrow window of variation for both autologous HSCT (R2=0.95, 0.98 and 0.94 for high, middle and low income categories, respectively) and allogeneic HSCT (R2=0.99, 0.96 and 0.95 for high, middle and low income categories, respectively) when breast cancer (autologous) and chronic myeloid leukemia (allogeneic) were excluded. Team density (R2=0.72) and team distribution (R2=0.51) were also associated with transplant rates. INTERPRETATION AND CONCLUSIONS: Transplant rates for HSCT in Europe are highly predictable. They are primarily influenced by GNI per capita. The absence of saturation and a nearly linear trend indicate that infrastructure lags behind medical needs. Isolated changes in single disease entities can easily be recognized.

Evolution of hematopoietic stem cell transplantation in Eastern and Western Europe from 1990 to 2003. A report from the EBMT activity survey.

Transplantation of hematopoietic stem cells (HSCT) has seen rapid expansion during the last decade. It is evident that there are differences between eastern and western European countries when this high cost procedure is concerned. In order to obtain more insight into the mechanisms associated with these differences, we compared the transplant rates (number of transplants per 10 million population) for allogeneic and autologous HSCT between selected eastern and western European countries and looked for factors associated with their differences. Data were obtained by the annual European Group for Blood and Marrow Transplantation (EBMT) activity survey for the period from 1990 to 2003. Transplant rates were substantially lower in eastern European countries for autologous, allogeneic, and unrelated HSCT throughout the observation period. The rapid increase in transplant rates during the 1990s occurred later in eastern European countries. Transplant rates continued to rise during the last three years in eastern European countries in contrast to a plateau in transplant rates in western European countries. There was a clear correlation between economic factors, measured as gross national income per capita, and transplant rates for low-income countries. There was also a clear correlation between team density (number of teams per 10 million population) and transplant rates. These data document that economic factors explain the differences in transplant rates between eastern and western European countries only in part. Another important factor seems to be the access to the therapeutic procedure. These data provide a basis for health care planning.

Relapse risk assessment of transplantation for patients with chronic myeloid leukaemia.

OBJECTIVE: To analyse the risk factors of relapse before bone marrow transplantation (BMT) and to present the prognostic information as good as possible. METHODS: A total of 3142 patients, who underwent the allogeneic blood or bone marrow transplantation between 1989 and 1997 and were documented in the European Group for Blood and Marrow transplantation (EBMT), were included. Six possible risk factors including type of donor, stage of disease, age, gender, donor-recipient sex combination and the waiting time from diagnosis to transplantation of relapse were considered. The time to relapse was analysed by Kaplan-Meier curves and Cox regression with stratification on prognostic factors that did not satisfy the Proportional Hazard Assumption. RESULTS: An amount of 447 patients relapsed out of all 3142 patients. The relapse rate was 14.2%. Type of donor and stage of disease showed a clear prognostic effect, but failed the proportional hazard assumption. Therefore, the data were stratified on the combination of type of donor and stage of disease. Within these strata an additional significant effect of age could be observed. Relative risk of age > or = 40 vs age < 40 was 1.32 (95% confidence interval 1.09 - 1.59). The prognostic model is summarized graphically. CONCLUSIONS: The combination of type of donor, stage of disease and age of recipient at transplantation are important prognostic factors for relapse after BMT.

The role of the EBMT activity survey in the management of hematopoietic stem cell transplantation. European Group for Blood Marrow Treansplantation.

Disease or treatment oriented registries form an integral part of modern medicine. They complement industry driven, corporate group sponsored and institutional research and are, together with prospective randomised trials cornerstones of modern evidence based medicine. Focus has been on rapid collection, analysis and dissemination of information on rare procedures with stress on patient outcome. In complex expensive procedures, such as hematopoietic stem cell transplants (HSCT), novel structures are required to catch outcome at team or national level. The annual activity survey of the European Group for Blood and Marrow Transplants EBMT forms such an instrument. Since 1990, EBMT has been collecting, on an annual basis, numbers of HSCT from the preceding year according to indication, donor type and stem cell source. The survey covers all European countries. In 1990, 143 teams reported 4,234 HSCT; in the year 2000, 619 teams reported 19,136 HSCT (33% allogeneic, 67% autologous). This information, which covers over 90% of all HSCT performed in Europe and is based on 132,963 HSCT (33% allogeneic, 67% autologous), gives a clear overview of current status and ongoing trends. It shows the general increase in HSCT from 1990 to 2000 with few exceptions, such as autologous HSCT for breast cancer and allogeneic HSCT for chronic myeloid leukemia. It illustrates the shift in technology from bone marrow as stem cell source in 1990 (100%) to peripheral blood in 2000 (96% of autologous, 53% of allogeneic HSCT). Supplemented by population data and economic factors (Gross national Product, Health Care Expenditures, Health Care systems) of the individual countries it allows comparison of transplant rates (Number of transplants per 10 million inhabitants), team densities (Number of transplant teams per 10 million inhabitants) and trends between countries. It permits quantification of the impact of economics and health care systems and provides a basis for quality control and allows assessment of the main factors influencing team decisions: evidence, disease prevalence, economics and expectations. As such, it is an essential tool for patient counselling and health care planning.

Economics, health care systems and utilization of haematopoietic stem cell transplants in Europe.

Transplantation of haematopoietic stem cells from blood or bone marrow (HSCT) has seen rapid expansion. Increased costs and quality concerns present a challenge for health care providers. Information on factors influencing HSCT utilization is necessary. Data on 113 827 patients (37 761 allogeneic HSCT and 76 066 autologous HSCT), collected from 580 centres in 35 European countries between 1990 and 1999, were used. Economic factors, e.g. gross national product per capita, health care expenditure per capita and type of health care system were correlated with transplant rates (numbers of HSCT per 10 million inhabitants), team density (numbers of transplant teams per 10 million inhabitants) and increase in transplant numbers for each country. Annual numbers of HSCT increased in all European countries from 4234 in 1990 to 18 720 in 1999 irrespective of health care system. Economic strength and team density were the main determinants for transplant rate. This report reflects changes over the last decade and current status of HSCT in Europe. Economic strength, team density and hitherto unknown factors influence dissemination of the technology within Europe. These data provide a basis for health care planning, regulatory aspects and future research.