The economic burden of posttransplant events in renal transplant recipients in Europe.

BACKGROUND: This study aims to describe the healthcare resource utilization and costs of managing renal posttransplant patients over 3 years posttransplant in nine European countries and to stratify them by year 1 glomerular filtration rate (GFR). METHODS: A retrospective observational and database analysis of renal transplant patients and a physician questionnaire study were conducted to collect recipient and donor characteristics, posttransplant events, and healthcare resource utilization related to these posttransplant events. In each country, local published costs were applied to the resource use identified. The results were stratified by the patient GFR reading at a time point 1 year after renal transplant. RESULTS: The database study identified 3,181 patients who met the inclusion criteria, along with 2,818 transplants carried out in the centers surveyed by questionnaire. Total 3-year costs derived from the questionnaire analysis vary depending on local treatment practices, from a minimum of &OV0556;33,602 per patient in the Czech Republic to &OV0556;77,461 per patient in the Netherlands. Consistently across countries, estimated costs appear to decrease with improved graft functioning status (increased GFR) at 1 year. The average 3-year costs, discounting immunosuppression therapy and certain posttransplant events, per patient with a GFR greater than or equal to 60 at 1 year are estimated to be around 35% lower than those with 15≤GFR<30. CONCLUSION: This study demonstrates that in Europe, worsening posttransplant renal function may contribute to substantive increases in resource use, with some variation across regions. Therefore, management strategies that promote renal function after transplantation have the potential to provide important resource savings.

Abatacept or infliximab for patients with rheumatoid arthritis and inadequate response to methotrexate: an Italian trial-based and real-life cost-consequence analysis.

OBJECTIVES: In the 1-year, double-blind, placebo-controlled ATTEST trial, efficacy of abatacept or infliximab versus placebo was reported in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). The current study estimated trial-based and real-life costs of abatacept and infliximab for achieving pre-defined remission or low disease activity state (LDAS). METHODS: Quantity of drug, serious adverse event (SAE) rates and time (months) in remission or LDAS were taken from ATTEST for the trial-based calculation to derive a cost per remitting/LDAS patient and a cost per patient-month in remission/LDAS. Trial-based and real-life scenarios were performed. RESULTS: The annual trial-based costs per remitting/LDAS patient were €70.238/€37.208 for abatacept and €85.565/€46.602 for infliximab. In the first 6 months of the ATTEST trial, costs per patient-month in remission/LDAS were higher for abatacept (€11.024 and €6.018, respectively), relative to infliximab (€8.347 and €4.174, respectively). Over the full 12-month trial period cost per month in remission/LDAS estimates were only slightly in favour of infliximab (€6.959/€3.625) relative to abatacept (€7.297/€3.909). Assuming extension of treatment under real life conditions the cost per month in remission/LDAS turned substantially in favour of abatacept (€5.321/€2.819), as compared to infliximab (€7.189/€3.916). The higher initiation cost for abatacept to achieve remission/LDAS would be offset after a total 14.6 and 16.1 months of treatment, respectively, if treatment extended beyond 6 months under real-life conditions. These results proved to be robust when it was assumed that the (i) sharing of vials across patients completely averted infliximab wastage, (ii) AE risks were similar and (iii) onset of response was slower for abatacept. CONCLUSIONS: Our findings suggest a lower cost-consequence for abatacept during real-life treatment.

Characterizing the relationship between health utility and renal function after kidney transplantation in UK and US: a cross-sectional study.

BACKGROUND: Chronic allograft nephropathy (CAN) occurs in a large share of transplant recipients and it is the leading cause of graft loss despite the introduction of new and effective immunosuppressants. The reduction in renal function secondary to immunologic and non-immunologic CAN leads to several complications, including anemia and calcium-phosphorus metabolism imbalance and may be associated to worsening Health-Related Quality of Life. We sought to evaluate the relationship between kidney function and Euro-Qol 5 Dimension Index (EQ-5Dindex) scores after kidney transplantation and evaluate whether cross-cultural differences exist between UK and US. METHODS: This study is a secondary analysis of existing data gathered from two cross-sectional studies. We enrolled 233 and 209 subjects aged 18-74 years who received a kidney transplant in US and UK respectively. For the present analysis we excluded recipients with multiple or multi-organ transplantation, creatinine kinase ≥200 U/L, acute renal failure, and without creatinine assessments in 3 months pre-enrollment leaving 281 subjects overall. The questionnaires were administered independently in the two centers. Both packets included the EQ-5Dindex and socio-demographic items. We augmented the analytical dataset with information abstracted from clinical charts and administrative records including selected comorbidities and biochemistry test results. We used ordinary least squares and quantile regression adjusted for socio-demographic and clinical characteristics to assess the association between EQ-5Dindex and severity of chronic kidney disease (CKD). RESULTS: CKD severity was negatively associated with EQ-5Dindex in both samples (UK: ρ= -0.20, p=0.02; US: ρ= -0.21, p=0.02). The mean adjusted disutility associated to CKD stage 5 compared to CKD stage 1-2 was Δ= -0.38 in the UK sample, Δ= -0.11 in the US sample and Δ= -0.22 in the whole sample. The adjusted median disutility associated to CKD stage 5 compared to CKD stage 1-2 for the whole sample was 0.18 (p<0.01, quantile regression). Center effect was not statistically significant. CONCLUSIONS: Impaired renal function is associated with reduced health-related quality of life independent of possible confounders, center-effect and analytic framework.

Cost-effectiveness of saxagliptin (Onglyza®) in type 2 diabetes in Sweden.

AIM: The objective of this study was to investigate the cost-effectiveness of saxagliptin (Onglyza(®)), a DPP-4 inhibitor, plus metformin compared with a sulphonylurea (SU) (Glipizide) plus metformin in Swedish patients not well controlled on metformin alone. METHODS: Data from a 52-week clinical trial comparing saxagliptin and glipizide in combination with metformin was used in a simulation model to estimate long term complications in a cohort of type 2 diabetes patients. The model estimates the incidence of microvascular and macrovascular complications, diabetes-specific mortality, all-cause mortality, and ultimately, costs and quality-adjusted life years (QALYs) associated with the investigated treatment strategies. Costs and QALYs were estimated for a lifetime time horizon. RESULTS: Compared with SU+metformin, the cost per QALY gained with saxagliptin+metformin is approximately SEK 91,000. Patients on saxagliptin+metformin gain 0.10 QALYs on average, at an incremental cost of around SEK 9500. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSIONS: This study demonstrates that, over a patient's lifetime, the addition of saxagliptin to metformin is associated with improvements in quality-adjusted life years compared with SU in patients with type 2 diabetes. Saxagliptin treatment is a cost-effective treatment alternative for type 2 diabetes in patients not well-controlled on metformin alone.

Cost-effectiveness of atazanavir/ritonavir compared with lopinavir/ritonavir in treatment-naïve human immunodeficiency virus-1 patients in Sweden.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of atazanavir/ritonavir (atazanavir/r) versus lopinavir/ritonavir (lopinavir/r) in treatment-naïve human immunodeficiency virus-1 (HIV-1) patients in Sweden for whom efavirenz is not suitable. METHODS: A Markov model was developed to predict the lifetime outcomes of atazanavir/r and lopinavir/r in terms of quality-adjusted life years (QALYs) and total costs. The model was structured to focus on treatment lines--how patients progress from first- to second-, and then to third-line treatment. Model inputs were derived directly from clinical trials, such as the CASTLE study (a 96-week head-to-head trial in first-line therapy), and from the Framingham risk-equation. The analysis was conducted from a payer perspective and included extensive scenario and probabilistic sensitivity analyses. RESULTS: The model predicted atazanavir/r to save 0.16 (95% confidence interval (CI) 0.00 to 0.33) QALYs and reduce total costs by -202,896 SEK (95% CI -332,156 to -81,644 SEK) over a lifetime horizon. Probabilistic sensitivity analyses showed that atazanavir/r had a 100% probability to be cost-effective at a willingness to pay of 200,000 SEK per QALY. CONCLUSION: The results indicate that atazanavir/r is cost-saving and more effective compared to lopinavir/r for patients who have previously not been exposed to antiretroviral drugs in Sweden.

Cost-effectiveness of atypical antipsychotics for the management of schizophrenia in the UK .

OBJECTIVE: To evaluate the cost-effectiveness of atypical antipsychotic treatment sequences for the management of stable schizophrenia in the UK. RESEARCH DESIGN AND METHODS: A Markov model was developed to assess the cost per quality-adjusted life year (QALY) gained from 12 alternative treatment sequences each containing two of four atypical antipsychotics (aripiprazole, olanzapine, quetiapine and risperidone), followed by clozapine. The main model parameters were populated with data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and a recent trial comparing aripiprazole with olanzapine. Patients enter the model with stable schizophrenia and may relapse, discontinue or continue and experience adverse events (AEs), or develop diabetes. Population mortality was adjusted for schizophrenia and diabetes. Utility decrements applied to stable schizophrenia, relapse, diabetes and treatment-related AEs were taken from a direct UK utility elicitation study. Resource use and unit costs were taken from published sources. A time horizon of 10 years was adopted. Results are based on 10,000 probabilistic iterations of the model. RESULTS: Aripiprazole followed by risperidone produced the greatest number of QALYs, an additional 0.03 compared with risperidone followed by olanzapine, at an incremental cost of £257 (incremental cost/QALY: £9,440). Aripiprazole followed by risperidone had the greatest probability among evaluated sequences of being cost-effective at a threshold of >£10,000/QALY. All other strategies were dominated by at least one of these strategies. The impact of lower pricing for risperidone (based on generic availability) did not impact results. CONCLUSIONS: Modelling the cost-effectiveness of different treatment sequences for stable schizophrenia is appropriate given that patients rarely remain on one treatment for long periods. The treatment sequence aripiprazole followed by risperidone was the most cost-effective option for patients with stable schizophrenia in the UK.

Cost-effectiveness of primary cytology and HPV DNA cervical screening.

Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3-5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly.

Cost-effectiveness of peginterferon alfa-2b in combination with ribavirin as initial treatment for chronic hepatitis C in Sweden.

The aim of the study was to assess the cost-effectiveness of peginterferon alfa-2b (pegIFN) compared to interferon alfa-2b (IFN), both in combination with ribavirin, as initial therapy for chronic hepatitis C in Sweden. A computer based Markov model describing the natural course of chronic hepatitis C was used to assess costs and quality-adjusted life-y (QALY) for the treatment strategies. Study population was a cohort of hepatitis C patients from the age of 43 y until death. Natural history and response data were obtained from the literature and from Swedish clinical experts. Costs were obtained from different health care providers in Sweden and based on Swedish clinical practice. In our base case analysis for genotype 1 patients, pegIFN plus ribavirin therapy generated 0.29 incremental QALYs and was cost saving (dominant strategy). Corresponding results for genotype 2/3 patients were 0.09 QALYs at an incremental cost of 941 euros (10,500 euros/QALY). A probabilistic sensitivity analysis was performed to study the stability of our results. From the results we conclude that for genotype 1 patients treatment with pegIFN and ribavirin increased quality-adjusted life expectancy and was cost-effective as initial therapy for hepatitis C. The cost-effectiveness for patients infected with genotype 2/3 was less obvious.

Diffusion and economic consequences of health technologies in prostate cancer care in Sweden, 1991-2002.

OBJECTIVE: To describe the diffusion of six main health technologies used for management of prostate cancer, to estimate the economic consequences of technological changes, and to explore factors behind the diffusion. METHODS: Data describing the diffusion 1991-2002 were obtained from population-based databases. Costs were obtained from Linköping University Hospital and Apoteket AB. Factors affecting the diffusion of the technologies were explored. RESULTS: Utilization of technologies with a curative and/or palliative aim has increased over time, except for surgical castration. PSA-tests are used increasingly. The total cost of the study technologies has increased from 20 million euros in 1991 to 65 million euros in 2002. Classification of radical prostatectomy revealed a profile associated with a slow/limited diffusion, while classification of PSA-tests revealed a profile associated with a rapid/extensive diffusion. CONCLUSIONS: Several technological changes in the management of prostate cancer have occurred without proven benefits and have contributed to increased costs. There are other factors, besides scientific evidence, that have an impact on the diffusion. Consequently, activities aimed at facilitating an appropriate diffusion of new technologies are needed. The analytical framework used here may be helpful in identifying technologies that are likely to experience inappropriate diffusion and therefore need particular attention.

The estimated economic value of the welfare loss due to prostate cancer pain in a defined population.

The aim of the study reported here was to estimate the economic value of the welfare loss due to prostate cancer pain by estimating the extent to which pain affects health-related quality of life among patients with prostate cancer. The material consisted of a point estimate of health status among men with prostate cancer in a well-defined population of 200000 males. Clinical data concerning the disease at diagnosis (extracted from patients' records and the Regional Prostate Cancer Registry), and health utility ratings (using EuroQol) were obtained from 1 156 males with prostate cancer. A descriptive model showed that optimal treatment that would reduce pain to zero during the whole episode of disease would add on average 0.85 quality-adjusted life years (QALY) to every man with prostate cancer. Based on an estimate of the willingness to pay for a QALY the economic value of this welfare loss due to prostate cancer pain is in the magnitude of Euro 86 600 000 per year (Euro 19 800000 per million men in Sweden).

Costs and effects of prostate cancer screening in Sweden--a 15-year follow-up of a randomized trial.

OBJECTIVE: To estimate the lifetime cost per detected potentially curable cancer and the economic impact on healthcare of repeated screening for prostate cancer in Sweden in a cohort of men aged 50-69 years. MATERIAL AND METHODS: All 9171 men in a geographically defined population were included: 1492 were randomized to screening in four rounds every third year and 7679 constituted a control group. Digital rectal examination and prostate-specific antigen screening in different combinations were used as diagnostic measures. Costs associated with administration of the screening programme, loss of patient time, diagnostic measures and management strategies were included. A decision model was developed to calculate the total cost of the programme. RESULTS: The incremental cost per extra detected localized cancer was 168,000 SEK and per potentially curable cancer 356,000 SEK. Introducing this screening programme for prostate cancer in Sweden would incur 244 million SEK annually in additional costs for screening and treatment compared to a non-screening strategy. CONCLUSION: There is still no scientific evidence that patients will benefit from screening programmes. Prostate cancer screening would probably be perceived as cost-effective if potentially curable patients gained on average at least 1 year of survival.

Technological changes in the management of prostate cancer result in increased healthcare costs--a retrospective study in a defined Swedish population.

OBJECTIVE: In two previous studies we calculated direct costs for men with prostate cancer who died in 1984-85 and 1992-93, respectively. We have now performed a third cost analysis to enable a longitudinal cost comparison. The aim was to calculate direct costs for the management of prostate cancer, describe the economic consequences of technological changes over time and estimate total direct costs for prostate cancer in Sweden. MATERIAL AND METHODS: A total of 204 men in a defined population with a diagnosis of prostate cancer and who died in 1997-98 were included. Data on utilization of health services were extracted from clinical records from time of diagnosis to death from a university hospital and from one county hospital in the county of Ostergötland. RESULTS: The average direct cost per patient has been nearly stable over time (1984-85: 143 000 SEK; 1992-93: 150 000 SEK; 1997-98: 146 000 SEK). The share of costs for drugs increased from 7% in 1992-93 to 17% in 1997-98. The total direct costs for prostate cancer in Sweden have increased over time (1994-85: 610 MSEK; 1992-93: 860 MSEK; 1997-98: 970 MSEK). CONCLUSIONS: Two-thirds of the total cost is incurred by inpatient care. The share of the total costs for drugs is increasing due to increased use of gonadotrophin-releasing hormone analogues. Small changes in average direct costs per patient despite greater use of technology are explained by the fact that more prostate cancers are detected at the early stages.

Comparison of hemodialysis and peritoneal dialysis--a cost-utility analysis.

OBJECTIVE: Our aim was to compare both health-related quality of life and costs for hemodialysis (HD) and peritoneal dialysis (PD) in a defined population. DESIGN: Decision-tree modeling to estimate total costs and effects for two treatment strategies, HD and PD, among patients with chronic kidney failure, for 5 years following the start of treatment. Courses of events and health-care consumption were mapped in a retrospective matched-record study. Data on health status were obtained from a matched population by a quality-of-life questionnaire (EuroQol). The study has a societal perspective. SETTING: All dialysis departments in the southeastern health-care region of Sweden. PATIENTS: 136 patients with kidney failure, comprising 68 matched pairs, were included in a retrospective record study; 81 patients with kidney failure, comprising 27 matched triplets, were included in a prospective questionnaire study. MAIN OUTCOME MEASURES: Cost per life year and cost per quality-adjusted life year. RESULTS: The cost per quality-adjusted life year for PD was lower in all analyzed age groups. There was a 12% difference in the age group 21-40 years, a 31% difference in the age group 41-60 years, and an 11% difference in the age group 61+ years. Peritoneal dialysis and HD resulted in similar frequencies of transplantation (50% and 41%, respectively) and expected survival (3.58 years and 3.56 years, respectively) during the first 5 years after the initiation of treatment. CONCLUSION: The cost-utility ratio is most favorable for PD as the primary method of treatment for patients eligible for both PD and HD.