Policy evaluation in diabetes prevention and treatment using a population-based macro simulation model: the MICADO model.

AIMS: To test a simulation model, the MICADO model, for estimating the long-term effects of interventions in people with and without diabetes. METHODS: The MICADO model includes micro- and macrovascular diseases in relation to their risk factors. The strengths of this model are its population scope and the possibility to assess parameter uncertainty using probabilistic sensitivity analyses. Outcomes include incidence and prevalence of complications, quality of life, costs and cost-effectiveness. We externally validated MICADO's estimates of micro- and macrovascular complications in a Dutch cohort with diabetes (n = 498,400) by comparing these estimates with national and international empirical data. RESULTS: For the annual number of people undergoing amputations, MICADO's estimate was 592 (95% interquantile range 291-842), which compared well with the registered number of people with diabetes-related amputations in the Netherlands (728). The incidence of end-stage renal disease estimated using the MICADO model was 247 people (95% interquartile range 120-363), which was also similar to the registered incidence in the Netherlands (277 people). MICADO performed well in the validation of macrovascular outcomes of population-based cohorts, while it had more difficulty in reflecting a highly selected trial population. CONCLUSIONS: Validation by comparison with independent empirical data showed that the MICADO model simulates the natural course of diabetes and its micro- and macrovascular complications well. As a population-based model, MICADO can be applied for projections as well as scenario analyses to evaluate the long-term (cost-)effectiveness of population-level interventions targeting diabetes and its complications in the Netherlands or similar countries.

Cost-effectiveness of two endovascular treatment strategies vs intravenous thrombolysis.

OBJECTIVE: To assess the cost-effectiveness of endovascular treatment against intravenous thrombolysis (IVT) when varying assumptions concerning its effectiveness. METHODS: We developed a health economic model including a hypothetical population consisting of patients with ischemic stroke, admitted within 4.5 h from onset, without contraindications for IVT or intra-arterial treatment (IAT). A decision tree and life table were used to assess 6-month and lifetime costs (in Euros) and effects in quality-adjusted life years treatment with IVT alone, IAT alone, and IVT followed by IAT if the patient did not respond to treatment. Several analyses were performed to explore the impact of considerable uncertainty concerning the clinical effectiveness of endovascular treatment. RESULTS: Probabilistic sensitivity analysis demonstrated a 54% probability of positive incremental lifetime effectiveness of IVT-IAT vs IVT alone. Sensitivity analyses showed significant variation in outcomes and cost-effectiveness of the included treatment strategies at different model assumptions. CONCLUSIONS: Acceptable cost-effectiveness of IVT-IAT compared to IVT will only be possible if recanalization rates are sufficiently high (>50%), treatment costs of IVT-IAT do not increase, and complication rates remain similar to those reported in the few randomized studies published to date. Large randomized studies are needed to reduce the uncertainty concerning the effects of endovascular treatment.

Do centres with well-developed protocols, training and infrastructure have higher rates of thrombolysis for acute ischaemic stroke?

BACKGROUND: The introduction of intravenous thrombolysis with recombinant tissue Plasminogen Activator (rt-PA) has greatly improved the effectiveness of acute ischaemic stroke care. However, in most hospitals only 2-10% of all admitted stroke patients are treated with thrombolysis. AIM: The purpose of this study is to identify if available protocols, training and infrastructure influence the thrombolysis rate. DESIGN: Cohort study of 12 hospitals in the Netherlands. METHODS: In a cohort of patients admitted with acute stroke within 24 h from onset of symptoms, data were obtained. Stroke service characteristics of 12 hospitals were acquired through structured interviews with intra- and extramural representatives, in order to asses (i) protocols, (ii) training and (iii) complexity of infrastructure. Data were analysed with multi-level logistic regression to relate the likelihood of treatment with thrombolysis to availability and completeness of protocols, training and infrastructure both outside (extramural) and inside (intramural) each centre. RESULTS: Overall 5515 patients were included in the study. Thrombolysis rates varied from 5.7% to 21.7%. An association was observed between thrombolysis rates and extramural training [odds ratio (OR): 1.11; 95% confidence interval (CI): 0.99-1.25] and availability of intramural protocols (OR: 1.46; 95% CI: 1.12-1.91). After adjustment for hospital size and teaching vs. nonteaching hospital, these associations became stronger; extramural training [adjusted OR (aOR): 1.14; 95% CI: 1.01-1.30] and availability of intramural protocols (aOR: 1.77; 95% CI: 1.30-2.39). CONCLUSIONS: Extramural training and intramural protocols are important tools to increase thrombolysis rates for acute ischaemic stroke in hospitals. Intramural protocols and extramural training should be aimed at all relevant professionals.

Priority setting using multiple criteria: should a lung health programme be implemented in Nepal?

OBJECTIVES: To identify and weigh the various criteria for priority setting, and to assess whether a recently evaluated lung health programme in Nepal should be considered a priority in that country. METHODS: Through a discrete choice experiment with 66 respondents in Nepal, the relative importance of several criteria for priority setting was determined. Subsequently, a set of interventions, including the lung health programme, was rank ordered on the basis of their overall performance on those criteria. RESULTS: Priority interventions are those that target severe diseases, many beneficiaries and people of middle-age, have large individual health benefits, lead to poverty reduction and are very cost-effective. Certain interventions in tuberculosis control rank highest. The lung health programme ranks 13th out of 34 interventions. CONCLUSION: This explorative analysis suggests that the lung health programme is among the priorities in Nepal when taking into account a range of relevant criteria for priority setting. The multi-criteria approach can be an important step forward to rational priority setting in developing countries.

Patient-centred and professional-directed implementation strategies for diabetes guidelines: a cluster-randomized trial-based cost-effectiveness analysis.

AIMS: Economic evaluations of diabetes interventions do not usually include analyses on effects and cost of implementation strategies. This leads to optimistic cost-effectiveness estimates. This study reports empirical findings on the cost-effectiveness of two implementation strategies compared with usual hospital outpatient care. It includes both patient-related and intervention-related cost. PATIENTS AND METHODS: In a clustered-randomized controlled trial design, 13 Dutch general hospitals were randomly assigned to a control group, a professional-directed or a patient-centred implementation programme. Professionals received feedback on baseline data, education and reminders. Patients in the patient-centred group received education and diabetes passports. A validated probabilistic Dutch diabetes model and the UKPDS risk engine are used to compute lifetime disease outcomes and cost in the three groups, including uncertainties. RESULTS: Glycated haemoglobin (HbA(1c)) at 1 year (the measure used to predict diabetes outcome changes over a lifetime) decreased by 0.2% in the professional-change group and by 0.3% in the patient-centred group, while it increased by 0.2% in the control group. Costs of primary implementation were < 5 Euro per head in both groups, but average lifetime costs of improved care and longer life expectancy rose by 9389 Euro and 9620 Euro, respectively. Life expectancy improved by 0.34 and 0.63 years, and quality-adjusted life years (QALY) by 0.29 and 0.59. Accordingly, the incremental cost per QALY was 32 218 Euro for professional-change care and 16 353 for patient-centred care compared with control, and 881 Euro for patient-centred vs. professional-change care. Uncertainties are presented in acceptability curves: above 65 Euro per annum the patient-directed strategy is most likely the optimum choice. CONCLUSION: Both guideline implementation strategies in secondary care are cost-effective compared with current care, by Dutch standards, for these patients. Additional annual costs per patient using patient passports are low. This analysis supports patient involvement in diabetes in the Netherlands, and probably also in other Western European settings.

Implementing global knowledge in local practice: a WHO lung health initiative in Nepal.

Clinical practice guidelines are used widely to improve the quality of primary health care in different health systems, including those of low-income countries. Often developed at international level and adapted to national contexts to increase the feasibility of effective uptake, guideline initiatives aim to transfer global scientific knowledge into local practice. The WHO's Practical Approach to Lung Health (PAL) is an example of such an initiative and is currently being developed to improve the quality of care for youths and adults with respiratory diseases. We assessed ex-ante the feasibility of successful implementation of PAL in a pilot programme in rural Nepal, studying three components: the quality of the innovation (i.e. the guidelines), the effectiveness of the implementation strategy (i.e. training) and the receptiveness of the social system of health staff at all levels (i.e. social and organizational characteristics). We assessed the guideline innovation with the AGREE instrument for guidelines, the intended implementation strategy by critical comparison with literature on effective strategies, and the social system with both a stakeholder analysis and a descriptive analysis of the health care system at district level. This ex-ante assessment of an adaptive local implementation of international WHO guidelines showed that in July 2002 the 'implementability' of the package was challenged on the three components studied. To increase the chances of successful implementation, the national guideline development process should be improved and the implementation strategy needs to be upgraded. In order to successfully transfer global knowledge into local practice, we need to develop additional multifactorial sustained interventions that tackle other culture-specific and health system-specific barriers as well. The primary health workers are key informants for these barriers.

Cost-effectiveness of integrated stroke services.

BACKGROUND: Randomized trials have shown that integrating services for acute stroke care may lead to organizational improvements, higher efficiency and better patient outcomes in the acute phase. AIM: To compare the costs and effects of stroke services in an experimental group of patients compared to a group of patients receiving conventional care. DESIGN: Prospective non-randomized controlled trial. METHODS: We compared all consecutively hospitalized stroke patients in three experimental stroke service settings (Delft, Haarlem and Nijmegen, n = 411) with concurrent patients receiving conventional stroke care (n = 187) over 6 months follow-up. Main end-points were total costs per patient and total health-adjusted days per 100 patients as measured by the EuroQol-5D score during follow-up. RESULTS: Mean total costs per patient were 16,000 Euro (95%CI 14,670 Euro-16,930 Euro): 13,160 Euro in Delft, 16,790 Euro in Haarlem, 20,230 Euro in Nijmegen, and 13,810 Euro in the control regions. Early discharge in Delft saved about 2500 Euro hospital costs per patient. General patient health in Delft was significantly better than in the control regions; Haarlem and Nijmegen showed no difference in health. DISCUSSION: Our study confirms the potential to improve stroke outcomes in a cost-effective way in Dutch settings. This was seen in the group of patients in Delft, a complete and relatively simple stroke service, but not in two other regions with more complex stroke services. Important factors are reduction of hospital days and, most likely, adequate multidisciplinary rehabilitation.

Cost-effectiveness of glycemic control and ophthalmological care in diabetic retinopathy.

AIMS: Glycemic control and ophthalmological care are known to significantly diminish the risk of visual impairment and blindness by diabetic retinopathy (DRP). The (cost-)effectiveness of both strategies was studied to highlight their benefits for patients and care providers. METHODS: A computer analysis was developed, following the progression of DRP and the effectiveness of metabolic control and ophthalmological care continuously and individually in cohorts of type I and type II DM patients with divergent degrees of compliance. Costs relate to present medical charges in the Netherlands. RESULTS: Intensive glycemic control shortens the duration of blindness in a type I DM patient by 0.76 years, intensive ophthalmological care by 0.53 years. One year sight gain may cost 1126 euros by providing ophthalmological care and 50479 euros by glycemic control. The duration of blindness drops in a type II DM patient by 0.48 and 0.13 years, respectively, whereas the effectiveness decreases as the age of onset of DM rises. CONCLUSIONS: The vast majority of diabetic patients benefits from both intensive glycemic control and intensive ophthalmological care, but these cost-effective interventions which are not only complementary, but also substitute each other, require lasting, full compliance by all parties concerned.

Lifetime health effects and costs of diabetes treatment.

BACKGROUND: This article presents cost-effectiveness analyses of the major diabetes interventions as formulated in the revised Dutch guidelines for diabetes type 2 patients in primary and secondary care. The analyses consider two types of care: diabetes control and the treatment of complications, each at current care level and according to the guidelines. METHODS: A validated probabilistic diabetes model describes diabetes and its complications over a lifetime in the Dutch population, computing quality-adjusted life years and medical costs. Effectiveness data and costs of diabetes interventions are from observational current care studies and intensive care experiments. Lifetime consequences of in total sixteen intervention mixes are compared with a baseline glycaemic control of 10% HBA1C. RESULTS: The interventions may reduce the cumulative incidence of blindness, lower-extremity amputation, and end-stage renal disease by >70% in primary care and >60% in secondary care. All primary care guidelines together add 0.8 quality-adjusted life years per lifetime. CONCLUSION: In case of few resources, treating complications according to guidelines yields the most health benefits. Current care of diabetes complications is inefficient. If there are sufficient resources, countries may implement all guidelines, also on diabetes control, and improve efficiency in diabetes care.

Resource consumption and costs in Dutch patients with type 2 diabetes mellitus. Results from 29 general practices.

AIMS: The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non-medical costs of patients with Type 2 diabetes in The Netherlands. METHODS: Twenty-nine Dutch general practitioners provided information on all Type 2 diabetes patients in their practice (n = 1371), information on demography, clinical characteristics, treatment type, the presence of complications and the type and amount of medical consumption during the previous 6 months. Medical costs were analysed using multivariate linear regression. Estimates of costs seen in The Netherlands were based on these results plus information from other sources regarding costs of end-stage renal disease, appliances, travel and productivity loss. RESULTS: Although only 9% of patients were hospitalized within the previous 6 months, hospitalization costs represented one-third of the medical costs, drug costs 40% and ambulatory costs 26%. Patients using insulin, patients with macrovascular complications only or in combination with microvascular complications incurred higher medical costs than other patients. Age and hyperlipidaemia were also positively related to medical costs. When these results were combined with other data sources, we estimated that patients with Type 2 diabetes are responsible for pound365 500 000 (1 271 000 000 guilders) or 3.4% of the relevant parts of health care costs in 1998. The non-medical costs (travel costs, productivity costs) are limited: 52 500 000 (183 000 000 guilders). CONCLUSIONS: Independent determinants of the medical costs of Type 2 diabetes in The Netherlands include age, complications, insulin use and hyperlipidaemia.

[Calculation of costs of stroke, cost effectiveness of stroke units and secondary prevention in patients after a stroke, as recommended by revised CBO practice guideline 'Stroke']. / Berekening van kosten na een beroerte en kosteneffectiviteit van 'stroke units' en van secundaire preventie, zoals aanbevolen in de herziene CBO-richtlijn 'Beroerte'.

OBJECTIVE: Economic analyses have been part of the revision of the Dutch multi-disciplinary stroke guidelines. We evaluated the recommendations on stroke units and prevention of stroke recurrencies in terms of medical costs and health effects among stroke patients. DESIGN: Cost calculation. METHOD: Mathematical modelling of medical costs per patient and costs per life year gained without severe stroke (Rankin score (> 3)), by age and sex for each guideline. RESULTS: Lifetime costs of stroke depended on age and sex and vary between 84,000 and 292,000 Dutch guilders (HFL). The cost-effectiveness of stroke units decreases with age and varies between HFL 37,000 and HFL 60,200 with a large uncertainty range. Four of seven options in secondary prevention were cost-effective by previously established criteria (< HFL 40,000 per year gained without severe disease). Acetylsalicylic acid remained the drug of choice for monotherapy with dipyridamol as a second choice in patients without atrial fibrillation. Clopidogrel was not cost-effective at the current cost level. Anticoagulation after stroke in case of atrial fibrillation was cost-effective. CONCLUSIONS: Given a short hospital stay stroke units can be as affective as other hospital interventions. Acetylsalicylic acid is the most cost effective monotherapy for secondary prevention.

The evidence-based approach in health policy and health care delivery.

Evidence-based approaches are prominent on the national and international agendas for health policy and health research. It is unclear what the implications of this approach are for the production and distribution of health in populations, given the notion of multiple determinants in health. It is equally unclear what kind of barriers there are to the adoption of evidence-based approaches in health care practice. This paper sketches some developments in the way in which health policy is informed by the results from health research. It summarises evidence-based approaches in health at three impact levels: intersectoral assessment, national health care policy, and evidence-based medicine in everyday practice. Consensus is growing on the role of broad and specific health determinants, including health care, as well as on priority setting based on the burden of diseases. In spite of methodological constraints, there is a demand for intersectoral assessments, especially in health sector reform. Initiators of policy changes in other sectors may be held responsible for providing the evidence related to health. There are limited possibilities for priority setting at the national health care policy level. Hence, there is a decentralisation of responsibilities for resource use. Health care providers are encouraged to assume agency roles for both patients and society and asked to promote and deliver effective and efficient health care. Governments will have to design a national framework to facilitate their organisation and legal framework to enhance evidence-based health policy. Treatment guidelines supported by evidence on effectiveness and efficiency will be one essential element in this process. With the increasing number of advocates for the enhancement of population health in the policy arenas, evidence-based approaches provide the information and some of the tools to help with priority setting.

[Detailed analysis of the societal costs of diabetes mellitus]. / Gedetailleerde raming van de maatschappelijke kosten van diabetes mellitus.

OBJECTIVE: Estimation of the societal costs of diabetes and related complications in support of the revision of the diabetes guidelines. DESIGN: Retrospective and descriptive cross-sectional study. METHODS: Relative risks (RRs) of diabetes complications, by age, were determined by comparing patients with and without diabetes. Using existing 1994 General Practitioner registry data on prevalence, on costs of illnesses and on absenteeism, the contribution of diabetes to the costs of other illnesses was estimated on the basis of aetiological fractions calculated with the RRs found. Cost due to absenteeism by diabetes complications were calculated using the friction method. RESULTS: In 1994, the societal cost of diabetes were 1.67 milliard Dutch guilders (1.55-1.87; range determined by applying the 95% confidence intervals of the RRs; in Euro: 758 million (703-848). The costs due to absenteeism from work were almost 0.2 milliard. The medical costs of diabetes were 2.5% of the health care budget. The contribution of diabetes to the medical costs of cardiovascular diseases was 14%.

Diabetes nephropathy in the Netherlands: a cost effectiveness analysis of national clinical guidelines.

BACKGROUND: In the Netherlands a program on quality assurance in medical care has started in 1996. Clinical professionals, patient organizations and health services researchers formulate evidence based guidelines with a concomitant cost-effectiveness analysis. OBJECTIVES: To examine the cost-effectiveness of guideline recommendations for prevention of nephropathy in diabetes mellitus type 1 and 2. RESEARCH DESIGN: A semi-Markov compartment model was developed. Data from international publications on epidemiological surveys and randomized trials, together with national data on health care use and costs, were used to feed the model. A cohort of diabetes patients without renal disease enters the model. MEASURES: Complication (end-stage renal disease) free years, QALY's, and life-time medical costs per patient treated according to guideline recommendations or current anti-diabetic strategy. RESULTS: Guideline treatment for type 1 diabetes yields 4.2 complication free life years, at a cost-effectiveness ratio of 13 500 (Dutch guilders) NLG per QALY. Type 2 diabetes patients gain 0.2 complication free life years at a cost-effectiveness ratio of 31 000 NLG per QALY. CONCLUSION: Guideline development for diabetes nephropathy, with concomitant cost-effectiveness calculations, has resulted in a transparent guideline with explicit information on long-term cost and effects. The project has brought health care providers and health services researchers together.

Potential impact of global climate change on malaria risk.

The biological activity and geographic distribution of the malarial parasite and its vector are sensitive to climatic influences, especially temperature and precipitation. We have incorporated General Circulation Model-based scenarios of anthropogenic global climate change in an integrated linked-system model for predicting changes in malaria epidemic potential in the next century. The concept of the disability-adjusted life years is included to arrive at a single measure of the effect of anthropogenic climate change on the health impact of malaria. Assessment of the potential impact of global climate change on the incidence of malaria suggests a widespread increase of risk due to expansion of the areas suitable for malaria transmission. This predicted increase is most pronounced at the borders of endemic malaria areas and at higher altitudes within malarial areas. The incidence of infection is sensitive to climate changes in areas of Southeast Asia, South America, and parts of Africa where the disease is less endemic; in these regions the numbers of years of healthy life lost may increase significantly. However, the simulated changes in malaria risk must be interpreted on the basis of local environmental conditions, the effects of socioeconomic developments, and malaria control programs or capabilities.

Stroke trends in an aging population. The Technology Assessment Methods Project Team.

BACKGROUND AND PURPOSE: Trends in stroke incidence and survival determine changes in stroke morbidity and mortality. This study examines the extent of the incidence decline and survival improvement in the Netherlands from 1979 to 1989. In addition, it projects future changes in stroke morbidity during the period 1985 to 2005, when the country's population will be aging. METHODS: A state-event transition model is used, which combines Dutch population projections and existing data on stroke epidemiology. Based on the clinical course of stroke, the model describes historical national age- and sex-specific hospital admission and mortality rates for stroke. It extrapolates observed trends and projects future changes in stroke morbidity rates. RESULTS: There is evidence of a continuing incidence decline. The most plausible rate of change is an annual decline of -1.9% (range, -1.7% to -2.1%) for men and -2.4% (range, -2.3% to -2.8%) for women. Projecting a constant mortality decline, the model shows a 35% decrease of the stroke incidence rate for a period of 20 years. Prevalence rates for major stroke will decline among the younger age groups but increase among the oldest because of increased survival in the latter. In absolute numbers this results in an 18% decrease of acute stroke episodes and an 11% increase of major stroke cases. CONCLUSIONS: The increase in survival cannot fully explain the observed mortality decline and, therefore, a concomitant incidence decline has to be assumed. Aging of the population partially outweighs the effect of an incidence decline on the total burden of stroke. Increase in cardiovascular survival leads to a further increase in major stroke prevalence among the oldest age groups.

Substantia nigra projections to the reticular formation, superior colliculus and central gray in the rat, cat and monkey.

After horseradish peroxidase injections in different parts of the lower brain stem retrogradely labeled neurons were observed in the substantia nigra, mainly ipsilateral pars reticulata. These findings demonstrate that the substantia nigra projects not only to the striatum and thalamus but also to brain stem areas which give rise to descending spinal projections. These nigral projections to brain stem structures may play an important role in a variety of behaviors and may be involved in clinical syndromes associated with nigral lesions.