Eight-year trajectories of changes in health-related quality of life in knee osteoarthritis: Data from the Osteoarthritis Initiative (OAI).

BACKGROUND: Knee osteoarthritis (OA) worsens health-related quality of life (HRQoL) but the symptom pathway varies from person to person. We aimed to identify groups of people with knee OA or at its increased risk whose HRQoL changed similarly. Our secondary aim was to evaluate if patient-related characteristics, incidence of knee replacement (KR) and prevalence of pain medication use differed between the identified HRQoL trajectory groups. METHODS: Eight-year follow-up data of 3053 persons with mild knee OA or at increased risk were obtained from the public Osteoarthritis Initiative (OAI) database. Group-based trajectory modeling was used to identify patterns of experiencing a decrease of ≥10 points (Minimal Important Change, MIC) in the Quality of Life subscale of the Knee injury and Osteoarthritis Outcome Score compared to baseline. Multinomial logistic regression, Cox regression and generalized estimating equation models were used to study secondary aims. RESULTS: Four HRQoL trajectory groups were identified. Persons in the 'no change' group (62.9%) experienced no worsening in HRQoL. 'Rapidly' (9.5%) and 'slowly' worsening (17.1%) groups displayed an increasing probability of experiencing the MIC in HRQoL. The fourth group (10.4%) had 'improving' HRQoL. Female gender, higher body mass index, smoking, knee pain, and lower income at baseline were associated with belonging to the 'rapidly worsening' group. People in 'rapidly' (hazard ratio (HR) 6.2, 95% confidence interval (CI) 3.6-10.7) and 'slowly' worsening (HR 3.4, 95% CI 2.0-5.9) groups had an increased risk of requiring knee replacement. Pain medication was more rarely used in the 'no change' than in the other groups. CONCLUSIONS: HRQoL worsening was associated with several risk factors; surgical and pharmacological interventions were more common in the poorer HRQoL trajectory groups indicating that HRQoL does reflect the need for OA treatment. These findings may have implications for targeting interventions to specific knee OA patient groups.

Longterm Work Productivity Costs Due to Absenteeism and Permanent Work Disability in Patients with Early Rheumatoid Arthritis: A Nationwide Register Study of 7831 Patients.

OBJECTIVE: To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). METHODS: A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. RESULTS: Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. CONCLUSION: The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.

Impact of Alzheimer's disease on the family caregiver's long-term quality of life: results from an ALSOVA follow-up study.

PURPOSE: To examine caregivers' health-related quality of life (HRQoL) and well-being during the first 3 years after their family member's Alzheimer's disease (AD) diagnosis and assessed the relationship between caregivers' HRQoL, well-being, and the severity of AD. Further, to compare of caregivers' HRQoL to general population. METHODS: Longitudinal design (36 months) after AD diagnosis of 236 caregiver-patient dyads. Linear regression was used to assess age- and gender-adjusted association between repeated measurements of caregivers' HRQoL and the severity of AD. For comparison with general population, the National Health 2011 Health Examination Survey data was utilized. RESULTS: Caregivers had significantly lower HRQoL than age- and gender-standardized counterparts. Severity of AD was significantly (p < 0.05) associated with the mobility and depression dimensions of caregiver's HRQoL but not with the total HRQoL index score. CONCLUSIONS: Caregivers' HRQoL seems to deteriorate earlier than previously noted. The severity of AD has not that great impact on caregiver's HRQoL as assumed.

Use of Anti-Dementia Drugs in Relation to Change in Cognition, Behavior, and Functioning in Alzheimer's Disease over a Three-Year Period: Kuopio ALSOVA Study.

BACKGROUND: Alzheimer's disease (AD) is characterized by deterioration in cognition, decline in physical function, and increase in behavioral disturbances. These symptoms are associated with dependence. OBJECTIVE: We investigated the use of anti-dementia drugs in relation to change in cognition, function, and behavior over a 3-year period. METHODS: Data were collected as part of the prospective follow-up ALSOVA study. All study participants (n = 236) had very mild or mild AD at baseline. All participants and their informal caregivers underwent annual clinical and medication assessments. Repeated measures logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with anti-dementia drug use and disease progression measures over time. RESULTS: The overall prevalence of anti-dementia drug use remained stable (from 89% to 92%) during the follow-up period. The use of memantine and cholinesterase inhibitor-memantine combination treatment increased with disease severity. After adjustment for confounding, a one-point increase in the disease severity scale (CDR-SOB) was associated with 15.6% increased odds of memantine use. A one-point decrease in CERAD Neuropsychological battery (CERAD-NB) total score was associated with 2.4% increased odds of memantine use. The overall unadjusted rate of switching between anti-dementia drugs was 9.17 (95% CI 7.10 to 11.88) changes per 100 person-years. CONCLUSION: Nearly 90% of newly diagnosed persons with AD were prescribed anti-dementia drugs. Use of memantine was found to be associated with disease progression. Switching and use of anti-dementia drugs was consistent with Finnish and European clinical practice guidelines for AD.

Depressed Spousal Caregivers Have Psychological Stress Unrelated to the Progression of Alzheimer Disease: A 3-Year Follow-Up Report, Kuopio ALSOVA Study.

OBJECTIVE: To explore family caregiver (FC) long-term psychological distress after Alzheimer disease (AD) diagnosis in a family member. METHODS: FC (n = 236) and patients with AD were prospectively followed up to 36 months after AD diagnosis. FC psychological distress was evaluated using the General Health Questionnaire (GHQ). Furthermore, caregiver depressive symptoms and sense of coherence, along with AD patient measurements, were measured at baseline and annually. Generalized estimating equation models were applied to study associations of these baseline factors to caregiver GHQ. RESULTS: After 36 months of follow-up, spousal caregivers (SCs) GHQ was significantly higher (P < .001) than in the nonspousal caregivers (NSCs). The difference in GHQ scores was associated by depressive symptoms (P < .001) at baseline, and the depressed SCs have more severe distress than NSCs over the observation period. CONCLUSION: During longitudinal caregiving, spousal and depressed caregivers of patients with AD report higher and increasing psychological stress than nonspousal and nondepressed caregivers. Spousal relationship, caregivers' depressive symptoms, and the severity of patients' neuropsychological symptoms at the time of AD diagnosis predict the trajectory of psychological distress. The current study highlights the need for evaluating AD caregiver mental health and level of coping.

Economic impact of 13-valent pneumococcal conjugate vaccine in Finnish adults ≥50 years with underlying chronic medical conditions.

RATIONALE, AIMS AND OBJECTIVES: Invasive pneumococcal diseases (IPD) are associated with substantial burden in adults (≥50 years). Moreover, adults with vascular, metabolic or respiratory diseases have been shown to have a 3-6 times higher risk of IPD when compared with their healthy controls. These persons at higher risk are likely to benefit most from pneumococcal vaccinations. The 13-valent pneumococcal conjugate vaccine (PCV13) was recently introduced to prevent the 13 most prevalent serotypes causing invasive pneumococcal disease in adults. The objective of this study was to estimate the expected 5-year economic impact of targeted PCV13 vaccination compared with no vaccination in Finnish adults (≥50 years) at moderate or high risk for IPD. METHODS: A budget impact model was developed to predict the impact of PCV13 vaccination in terms of the costs and IPD events avoided for years 2012-2016. RESULTS: Approximately 35% of the 2.2 million Finns over 50 years of age can be considered to be at moderate or high risk for IPD because of underlying chronic medical conditions. Vaccination of these people with PCV13 could provide an estimated net budget savings of about €218 million compared with the current no-vaccination situation over the next 5 years. Among the risk groups considered, the largest absolute net savings (€66.2 million) could be expected to be obtained by vaccinating people with heart disease, due to its high prevalence in the target population. CONCLUSION: In Finland, the immunization with PCV13 vaccine, of adults (≥50 years) at moderate and high risk of IPD, is estimated to lead to substantial cost savings in the 5 years after vaccination.

Register-based predictors of adherence among new statin users in Finland.

BACKGROUND: Although register-based studies on statin adherence are increasing, for administrative data, little is known about the explanatory power of the predictors that explain adherence. OBJECTIVE: The aim was to explore the ability of variables in administrative data to predict statin adherence in an unselected, universally insured population and, especially, to explore dispensation delay (time elapsed between prescription and dispensation) and out-of-pocket costs as explanatory factors. METHODS: Statin initiators who were aged 45 to 75 years in 2000-2004 (n = 247, 051) were identified in the Finnish Prescription Register. First-year statin adherence was measured as the proportion of days covered (PDC). The effect of variables related to patient, health care, and payment was assessed with multivariable logistic regression. The C statistic was used to evaluate the explanatory power of different models. RESULTS: Overall, 54.6% of the cohort had good adherence (PDC ≥ 80%). The explanatory power of all the models was low (C = 0.666 for the full model). The multivariable models, including only payment variables, had a greater explanatory power (C = 0.627) than models with only patient (C = 0.602) or health care (C = 0.548) variables. A shorter dispensation delay and lower out-of-pocket costs predicted better adherence. Of other patient-related variables, age, presence of acute coronary syndrome, and use of cardiovascular medications were significant predictors of adherence. Type of statin and the prescriber's workplace were also significantly associated with adherence. CONCLUSIONS: Models based on administrative data do not provide useful prediction of statin adherence. Of the individual predictors, long dispensation delay may serve as a practical tool for identifying patients at risk of poor adherence. Increases in out-of-pocket costs predict nonadherence.

Economic evaluation of sequential treatments for follicular non-hodgkin lymphoma.

BACKGROUND: The cost-effectiveness analyses of follicular lymphoma (FL) treatments have focused on the second-line rituximab maintenance in patients with relapsed FL. The assessment of full FL treatment chain has been lacking. OBJECTIVE: The aim of this study was to assess the cost-effectiveness of FL treatment sequences. METHODS: Transitions between progression-free first-line treatment (PF1), progression-free second-line treatment (PF2), progression, and death health states were simulated with a probabilistic Markov model with half-cycle correction. At first, patients were assumed to be receiving rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) induction. The first-line RCHOP induction responders continued without (RCHOP) or with (RCHOPR) the first-line rituximab-maintenance treatment. In the case of PF1 failure, patients received RCOPR/bendamustine or RCOPR/COP according to the European Society for Medical Oncology guidance. In the case of PF2 failure, patients were expected to receive the best supportive care (BSC). The survivals and adverse events were estimated with direct and indirect comparisons. Health outcomes and Finnish payer (drug, drug administration, monitoring, test, progression, serious adverse event) costs valued in 2010 euros were discounted with 3% per annum. RESULTS: The mean discounted lifetime overall survival with FL was 9.6 to 11.5 years, quality-adjusted survival was 7.2 to 8.8 quality-adjusted life-years (QALYs), progression-free time was 7.7 to 10.2 years, and costs were €153,425 to €168,549, depending on the treatment sequence. The incremental cost-effectiveness ratios for RCHOPR→RCOPR/bendamustine→BSC, RCHOPR→RCOPR/COP→BSC, and RCHOP→RCOPR/bendamustine→BSC were €9575/€8014/€5900, €9881/€8310/€6013, and €8812/€7194/€5808, respectively, per QALY/life-year/progression-free year gained in comparison with RCHOP→RCOPR/COP→BSC. According to the cost-effectiveness acceptability frontier, the treatment of 61.8% to 72.7% patients with RCHOPR→RCOPR/bendamustine→BSC was cost effective at €20,000 to €30,000/QALY gained (expected value of perfect information [EVPI], €1287 to €1976/patient). The relative results were found to be robust in sensitivity analyses, and, in the direct comparison that included only head-to-head data, the first-line rituximab maintenance had 93.1% cost-effectiveness probability at €20,000/QALY gained (EVPI, €282/patient). CONCLUSION: Sequences that included first-line rituximab maintenance is and second-line bendamustine are potentially cost effective in the treatment of FL. LIMITATIONS: Because of data available, health outcomes of the first-line rituximab induction were excluded, the second-line patients on COP were assumed to incur the cost of COP, and the efficacy and adverse events of CHOP and the efficacy and adverse events of bendamustine were estimated indirectly according to a comparison of rituximab+bendamustine and RCHOP, and treatment benefits were truncated.

Sponsorship-related outcome selection bias in published economic studies of triptans: systematic review.

BACKGROUND: Economic studies funded by the pharmaceutical industry are more likely to report favorable results and recommendations for the sponsor's product than are studies funded by nonindustry establishments. PURPOSE: To determine whether clinical outcome data obtained from the same meta-analyses are used differently in various economic studies of oral triptans and whether there is an association between the study sponsorship and the choice of clinical outcome measure. DATA SOURCES: Economic studies of triptans were identified by updating a previously published systematic review. STUDY SELECTION: Twelve studies that used the same meta-analyses as the source of clinical outcome data were identified. DATA EXTRACTION: Two independent reviewers extracted the essential data from the identified studies. DATA SYNTHESIS: In the 12 appraised studies, 9 alternative measures of effectiveness were derived from the same meta-analyses. Eleven studies were industry-related, and in these the selected clinical outcome consistently favored the sponsor's product. Also the reported results suggested that the sponsor's product was more cost-effective than the competitors' products. LIMITATIONS: The cost-effectiveness of triptans is dependent on both the definition of clinical effectiveness and the treatment-related costs. Only bias related to the selection of the clinical outcome measure has been taken into account in this review. CONCLUSIONS: The results of published economic studies of triptans are conflicting and biased. There is a tendency to select clinical outcome measures that support the sponsor's product. This leads to concern about the possible poor applicability of these results in decision making.

Short-course adjuvant trastuzumab therapy in early stage breast cancer in Finland: cost-effectiveness and value of information analysis based on the 5-year follow-up results of the FinHer Trial.

BACKGROUND: Trastuzumab is a standard treatment of HER2-positive early breast cancer in many countries, and it is usually given as a one year adjuvant treatment. However, its cost-effectiveness has not been assessed in Finland. The Finland Herceptin (FinHer) trial has compared a shorter 9-week treatment protocol against no trastuzumab with promising results. The aim of this study was to assess the potential cost-effectiveness of the 9-week treatment based on the recently published five-year follow-up results of the FinHer trial. METHODS: An evaluation model of breast cancer treatment was constructed using fitted survival estimates and a long-term Markov model. The cost-effectiveness of 9-week adjuvant treatment was assessed in a Finnish setting, compared to treatment without trastuzumab. The analysis was performed from a societal perspective, and a 3% discount rate was applied for future costs and outcomes. Value of information analysis was performed to estimate the potential value of further research. RESULTS: According to the probabilistic analysis, the incremental cost-effectiveness ratio was €12 000 per quality adjusted life year (QALY), and €9300 per life year gained (LYG), when comparing adjuvant trastuzumab therapy to standard treatment without trastuzumab. The modelled incremental outcomes for trastuzumab treatment were 0.66 QALY and 0.85 LYG for a lifetime perspective. Value of information analysis showed that additional research on treatment effects would be most valuable for reducing uncertainty in the adoption decision. CONCLUSIONS: Adjuvant 9-week trastuzumab is likely to be a cost-effective treatment in the Finnish setting. Results from an ongoing trial comparing adjuvant 9-week treatment with the 12-month treatment will play a key role in addressing the uncertainty related to the treatment effect and potential cost-effectiveness of these two treatment protocols.

Budget impact analysis of trastuzumab in early breast cancer: a hospital district perspective.

OBJECTIVES: Adjuvant trastuzumab is widely used in HER2-positive (HER2+) early breast cancer, and despite its cost-effectiveness, it causes substantial costs for health care. The purpose of the study was to develop a tool for estimating the budget impact of new cancer treatments. With this tool, we were able to estimate the budget impact of adjuvant trastuzumab, as well as the probability of staying within a given budget constraint. METHODS: The created model-based evaluation tool was used to explore the budget impact of trastuzumab in early breast cancer in a single Finnish hospital district with 250,000 inhabitants. The used model took into account the number of patients, HER2+ prevalence, length and cost of treatment, and the effectiveness of the therapy. Probabilistic sensitivity analysis and alternative case scenarios were performed to ensure the robustness of the results. RESULTS: Introduction of adjuvant trastuzumab caused substantial costs for a relatively small hospital district. In base-case analysis the 4-year net budget impact was 1.3 million euro. The trastuzumab acquisition costs were partially offset by the reduction in costs associated with the treatment of cancer recurrence and metastatic disease. CONCLUSIONS: Budget impact analyses provide important information about the overall economic impact of new treatments, and thus offer complementary information to cost-effectiveness analyses. Inclusion of treatment outcomes and probabilistic sensitivity analysis provides more realistic estimates of the net budget impact. The length of trastuzumab treatment has a strong effect on the budget impact.

Cost-effectiveness of single agent, uptitration and switching statin treatment strategies for lipid lowering in Sweden.

OBJECTIVES: To assess which alternative treatment strategies are optimum in terms of cost-effectiveness (EUR/patient treated to target, EUR/PTT) in lowering cholesterol in high-risk patients with elevated LDL-cholesterol (LDL-C) in Sweden. METHODS: A probabilistic cost-effectiveness model was developed to estimate the mean expected costs and proportion of patients reaching goal attainment (defined as LDL-C < or =2.5 mmol/L [96.5 mg/dL]) at some point in time within a 52-week period following the initiation of statin therapy. Eight different statin treatment strategies were evaluated. Key data sources used in the modeling were the scientific literature, hospital tariffs and medicine price databases. RESULTS: Depending on baseline LDL-C and the willingness-to-pay per additional PTT, the cost-effective alternative is always found among four out of the eight assessed treatment strategies (i.e. Simva10 --> Simva20 --> Simva40, Rosu10, Simva20 --> Rosu10 --> Rosu20 --> Rosu40, or Simva20 --> Simva40 --> Rosu20 --> Rosu40). An important finding was that when LDL-C level exceed 4.0 mmol/L (154mg/dL) and when willingness to pay is less than 500 EUR per additional PTT, the optimal treatment strategy would be to initiate cholesterol-lowering treatment directly with rosuvastatin 10 mg. CONCLUSIONS: The results of this study indicate that the optimal approach to initiate lipid-lowering therapy would be to treat patients with the lower baseline LDL-C levels with the least costly treatment strategies, while initiating lipid-lowering treatment with a high-potency statin (rosuvastatin) in patients with moderately high or high baseline LDL-C levels. This recommendation can be assumed to be relevant particularly when the fact that after treatment initiation the majority of Swedish patients will not have any changes in their lipid-lowering medication or dose is taken into account. Finally, since only the short-term results are presented here, it would be valuable to conduct further studies of the long-term cost-effectiveness of different statin treatment strategies that focus on treatment persistence and LDL-C goal attainment in real practice.

Population-based health-economic evaluation of the secondary prevention of coronary heart disease in Finland.

OBJECTIVE: To evaluate the cost-effectiveness of generic atorvastatin 20 mg (A20), branded rosuvastatin 10 mg (R10), generic simvastatin 40 mg (S40) and the combination of generic S40 + branded ezetimibe 10 mg (S40 + EZ10) for the secondary prevention of coronary heart disease (CHD) in Finnish patients not meeting the target goal of low-density lipoprotein cholesterol (LDL-C) with S40. RESEARCH DESIGN AND METHODS: A probabilistic Markov model was employed to evaluate the costs and health outcomes of the different therapies based on the cardiovascular events avoided. The model included Framingham risk equations, Finnish population characteristics, event rates, quality of life estimates, resource use and unit costs. The LDL-C lowering efficacies were gathered from a systematic literature review, based on a search of Medline carried out in June 2008 (no time limit). MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life year (QALY) gained and incremental cost per life year gained (LYG). RESULTS: The efficacy (LDL-C decrease) gained from switching S40 to S40 + EZ10 was consistent in the literature review, whereas the LDL-C decrease gained from switching S40 to A20/R10 was uncertain. The incremental cost per QALY gained from switching generic S40 was lowest for S40 + EZ10 (22,841 euros [24,017 euros] and 26,595 euros [46,686 euros] for diabetic and non-diabetic men [women], respectively). The respective incremental cost per QALY gained for S40 + EZ10 vs. A20 were 19,738 euros (21,405 euros) and 23,596 euros (40,087 euros). A20 dominated R10. Based on the cost-effectiveness acceptability frontier with a willingness-to-pay value of 30,000 euros per QALY gained, the probability of cost-effectiveness for switching generic S40 to S40 + EZ10 was 100% for men and diabetic women. Sensitivity analyses showed that results were robust. CONCLUSIONS: In the Finnish secondary prevention population that is not at goal on S40, switching generic S40 to S40 + EZ10 is more cost-effective than switching S40 to generic A20 or R10.

Costs and quality of life effects of the first year of renal replacement therapy in one Finnish treatment centre.

OBJECTIVE: The main objective of the study was to assess the cost and quality of life (QoL) effects of elective dialysis patients during the first year of end-stage renal disease (ESRD) treatment in one Finnish treatment centre. METHODS: A prospective case-series study was performed involving all elective dialysis patients (n=29) in a Finnish dialysis unit during 2003-2004. Direct costs of ESRD treatment were obtained from the hospital database and the Social Insurance Institution. The QoL effects were measured at the initiation of treatment, at 6 and at 12 months using 15D, a generic QoL instrument. RESULTS: The average cost of ESRD treatment was 69,085 euro. The improvement in the patients' QoL score was statistically and clinically significant during the first treatment year. The most significant changes were seen in the dimensions of breathing and vitality. The condition of patients commencing haemodialysis (HD) was more severe than that of patients commencing peritoneal dialysis (PD) as indicated by worse residual kidney function and poorer quality of life at the initiation. CONCLUSIONS: In this small patient population, treatment of ESRD during the first year seemed to improve or maintain the QoL of the patients.

Economic evaluation of sunitinib malate in second-line treatment of metastatic renal cell carcinoma in Finland.

BACKGROUND: Cytokine therapy is currently used as first-line treatment of metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven efficacy after the failure of first-line cytokine therapy were not available. In recent clinical trials, sunitinib has been associated with good response rates in patients with mRCC. OBJECTIVE: The aim of this study was to analyze the cost-effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC compared with current routine clinical practice in Finland (ie, best supportive care [BSC], including palliative biochemotherapy). METHODS: A probabilistic decision-analytic model was developed to estimate the cost-effectiveness of sunitinib. Data were gathered from clinical trials, literature sources, and expert opinions, as well as from a local sample (n = 39) from 2 university hospitals in Finland. Clinical experts treating patients with mRCC in Finland provided the information on care practices of prescribing sunitinib. The analysis was conducted from the perspective of the health care payer in Finland. RESULTS: According to estimated incremental cost-effectiveness ratios (ICERs), 1 progression-free month gained cost euro4802 (2005 Euros); 1 life-year gained cost euro30,831; and 1 quality-adjusted life-year (QALY) gained cost euro43,698, compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was euro5543. When parameter uncertainty was considered, the probability of sunitinib being the more cost-effective choice of treatment was ~70% at the willingness-to-pay level of euro45,000/QALY gained. CONCLUSIONS: Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (euro/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments.

Plant stanol esters are potentially cost-effective in the prevention of coronary heart disease in men: Bayesian modelling approach.

BACKGROUND: Plant stanol esters in spreads have demonstrated efficacy in reducing serum cholesterol. The cost-effectiveness of plant stanol esters in the prevention of coronary heart disease, however, has remained unevaluated. DESIGN: A Bayesian modelling approach was applied to synthesize clinical evidence and evaluate the cost-effectiveness (Euro/quality-adjusted life years) of plant stanol esters in spread in the prevention of coronary heart disease based on published FINRISK and 4S risk functions. RESULTS: The regular use of plant stanol esters reduced total serum cholesterol by -0.362 mmol/l [95% credibility interval (CrI) -0.31 to -0.41]. The corresponding placebo-adjusted reduction attributable to stanol esters when combined with statin was -0.385 mmol/l (95% CrI -0.18 to -0.61). The cost-effectiveness estimations were assessed for men and women separately at four different initial ages at which the regular use of stanol esters was assumed to be started. The base case cost per quality-adjusted life years gained by using stanol esters regularly ranged from 7436 to 20,999 Euro in men and from 34,327 to 112,151 Euro in women based on the initial starting age. According to uncertainty analysis, there is over a 90% probability that the use of plant stanol esters is cost-effective for men inclusively and for 60-year-old and older women assuming that decision-makers' maximum willingness to pay per quality-adjusted life year is 50,000 Euro. CONCLUSIONS: A recommendation that plant stanol ester-containing spreads be used as a part of daily diet replacing regular spread could be viewed as potentially cost-effective public health policy in the prevention of CHD in all adult men and in older age-groups of women with total serum cholesterol levels of 5 mmol/l or greater.

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme.

BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent with demonstrated efficacy as therapy for glioblastoma multiforme (GBM) and anaplastic astrocytoma. TMZ has widely replaced the procarbazine, lomustine plus vincristine (PCV) combination for the treatment of malignant brain tumours as a result of its oral administration and favourable toxicity profile. OBJECTIVES: This study had three related aims. First, the cost effectiveness of TMZ (from the Finnish healthcare payer perspective) was compared with PCV in patients with GBM that had relapsed after primary treatment with surgery and radiotherapy. Second, the probability that TMZ is cost effective, compared with PCV, was estimated at different societal willingness-to-pay levels. Third, the value of new information for reducing the uncertainty related to the choice of treatment between TMZ and PCV was evaluated. METHODS: The cost effectiveness of TMZ and PCV was evaluated using a decision-modelling approach. Incremental cost-effectiveness ratios (ICERs) for cost per gained life-month, progression-free life-month and QALY were calculated. Various information sources were used to acquire parameter values for the model. The efficacy information of both treatments was derived from the medical literature, quality-of-life (QOL) estimates were gathered from Finnish neuro-oncologists using visual analogue scale methods, and data on the use of healthcare resources were collected from hospital databases. The exact prices for resource use were gained from the list of Finnish health service unit costs (year 2001 prices). The model was analysed using second-order Monte Carlo simulation. The value of new information on reducing uncertainty was analysed using the expected value of perfect information (EVPI) approach. RESULTS: According to the derived ICERs, 1 extra life-month gained with TMZ costs euro2367, 1 extra progression-free life-month costs euro2165, and 1 extra QALY costs euro32 471, compared with PCV, in the treatment of GBM. The probability of TMZ being the most cost-effective choice of treatment was >60% for all levels of willingness to pay >euro5000 per gained life-month. The respective probabilities were >75% for all levels of willingness to pay >euro10 000 per gained progression-free life-month and about 85% for all levels of willingness to pay >euro20 000 per gained quality-adjusted life-month. According to EVPI analysis, future research would potentially be cost effective if the costs of research were euro4.1 million (maximum). CONCLUSIONS: On the basis of this Finnish analysis, TMZ has a high probability of being more cost effective than PCV for patients with GBM. The addition of QOL aspects to the prolonging of survival increases the probability further.