Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in adult patients with Pompe disease.

BACKGROUND: Pompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease. METHODS: Survival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%. RESULTS: Substantial increases in survival were estimated - discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2. CONCLUSIONS: The availability of extended, prospectively collected, longitudinal observational data on the most important input parameters required to construct a cost-effectiveness model is quite exceptional for orphan diseases. The cost-effectiveness model showed substantial survival gains from ERT. Despite these substantial gains, ERT was not cost-effective in the treatment of adult Pompe disease because of the high cost of treatment.

Evidence-based guidelines, time-based health outcomes, and the Matthew effect.

BACKGROUND: Cardiovascular risk management guidelines are 'risk based'; health economists' practice is 'time based'. The 'medical' risk-based allocation model maximises numbers of deaths prevented by targeting subjects at high risk, for example, elderly and smokers. The time-based model maximises numbers of life years gained by treating the young and non-smokers, or 'the one who has will be given more' (Matthew 25:29). We explored practical consequences of risk- or time-based allocation. METHODS: We used epidemiological modelling to generate semi-quantitative scenarios comparing the distributional effects of allocating a fixed number of prescriptions of a (hypothetical) preventive cardiovascular drug ('CVStop') either to avert the maximum number of deaths (risk-based) or to save the maximum number of life years (time based) in the male Dutch population. We subsequently asked 123 Dutch guideline developers which distribution they preferred. RESULTS: Time- and risk-based allocations resulted in different distributions of the drug across the population. There were also differences in absolute numbers of life years gained and deaths averted, and in the distribution of these across the population. For example, risk-based allocation of 'CVStop' resulted in preferential treatment of elderly, leading to more deaths averted (mostly among 70 and above) but fewer life years gained, if compared with time-based allocation. The guideline developers experienced the choice dilemmas as difficult. No priority choice was dominant among the respondents. CONCLUSION: In evidence-based resource allocation the choice to save time or to avert deaths may introduce moral choices because of the various origins of increased disease risk. Evidence-based guideline development inevitably has moral implications.

Has the burden of depression been overestimated?

OBJECTIVE: To investigate whether high estimates of the burden of depression could be attributed to an overestimation of disability weights (reflecting more severe disability). METHODS: We derived disability weights that were tailored to prevalence data. Empirical disability data from a Dutch community survey was used to describe three classes of severity of depression and their proportional prevalence. We obtained valuations from experts for each class and calculated the overall disability weight for depression. FINDINGS: Expert valuations were similar to those of previous studies. The overall disability weight for depression was similar to other studies except the 1994 Dutch Burden of Disease Calculation, which it exceeded by 73%. The lower Dutch 1994 disability weight resulted from an overestimation of the proportion of mild cases of depression by experts (60% versus 27% observed in the empirical data used in the present study). CONCLUSION: This study found no indication that disability associated with depression was overestimated. The Dutch example showed the importance of tailoring disability weights to epidemiological data on prevalence.

The breast cancer related burden of morbidity and mortality in six European countries: the European Disability Weights project.

BACKGROUND: The burden of breast cancer expressed in Disability Adjusted Life Years (DALYs) was compared for six European countries and its sensitivity to different sources of variation examined. METHODS: DALYs were calculated using country-specific epidemiological data and European Disability Weights. Epidemiological data for 1996 were obtained for Denmark, England and Wales, France, The Netherlands, Spain and Sweden. Disability weights were empirically derived. RESULTS: Denmark and The Netherlands lost the largest number of DALYs (approximately 1100 DALYs per 100,000 women). They were followed by England (87% of the Danish burden), France (72%), Sweden (68%) and Spain (67%). 70 to 80% of the burden was caused by mortality. Cross-national variation in disease epidemiology was the largest source of variation in the burden of breast cancer. Variation in disability weights and uncertainty in epidemiological data had smaller effects. CONCLUSION: To compare the burden of breast cancer and most other types of cancer mortality rates provide sufficient information.

The use of models in the estimation of disease epidemiology.

OBJECTIVE: To explore the usefulness of incidence-prevalence-mortality (IPM) models in improving estimates of disease epidemiology. METHODS: Two artificial and four empirical data sets (for breast, prostate, colorectal, and stomach cancer) were employed in IPM models. FINDINGS: The internally consistent artificial data sets could be reproduced virtually identically by the models. Our estimates often differed considerably from the empirical data sets, especially for breast and prostate cancer and for older ages. Only for stomach cancer did the estimates approximate to the data, except at older ages. CONCLUSION: There is evidence that the discrepancies between model estimates and observations are caused both by data inaccuracies and past trends in incidence or mortality. Because IPM models cannot distinguish these effects, their use in improving disease estimates becomes complicated. Expert opinion is indispensable in assessing whether the use of these models improves data quality or, inappropriately, removes the effect of trends.