Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.

INTRODUCTION: Prior to investing in a large, multicentre randomised controlled trial (RCT), the National Institute for Health Research in the UK called for an evaluation of the feasibility and value for money of undertaking a trial on intravenous immunoglobulin (IVIG) as an adjuvant therapy for severe sepsis/septic shock. METHODS: In response to this call, this study assessed the clinical and cost-effectiveness of IVIG (using a decision model), and evaluated the value of conducting an RCT (using expected value of information (EVI) analysis). The evidence informing such assessments was obtained through a series of systematic reviews and meta-analyses. Further primary data analyses were also undertaken using the Intensive Care National Audit & Research Centre Case Mix Programme Database, and a Scottish Intensive Care Society research study. RESULTS: We found a large degree of statistical heterogeneity in the clinical evidence on treatment effect, and the source of such heterogeneity was unclear. The incremental cost-effectiveness ratio of IVIG is within the borderline region of estimates considered to represent value for money, but results appear highly sensitive to the choice of model used for clinical effectiveness. This was also the case with EVI estimates, with maximum payoffs from conducting a further clinical trial between £ 137 and £ 1,011 million. CONCLUSIONS: Our analyses suggest that there is a need for a further RCT. Results on the value of conducting such research, however, were sensitive to the clinical effectiveness model used, reflecting the high level of heterogeneity in the evidence base.

Patient perspective in health technology assessment of pharmaceuticals in Finland.

OBJECTIVES: The need to consider the patient perspective in health technology assessments (HTA) has been widely recognized. In July 2012, the Finnish Medicines Agency (Fimea) published a national recommendation for integrating the patient perspective into the HTAs of pharmaceuticals. The aim of this study is to describe the development of the recommendation for integrating the patient perspective into the HTA process of pharmaceuticals in Finland. METHODS: The development of the recommendation was based on a review of international recommendations and experiences of patient and public involvement in HTA. The draft recommendation was tested in two focus group discussions (n = 7 patients) and three individual interviews among diabetes patients (type 1 or 2) using long-acting insulin treatment. The recommendation was open for public consultation in April 2012 and revised according to the comments received. RESULTS: Patients will be involved in multiple stages of Fimea's HTA process. The recommendation includes step-by-step instructions on how to assess the patient perspective. The main focus is on qualitative interviews, which will be conducted at the beginning of the assessments to gain information, particularly on patient preferences and values, including positive and negative outcomes important to patients and ethical and social aspects of the medicine's use. CONCLUSIONS: The recommendation will act as a tool to integrate patients' experiences, needs and preferences into Fimea's HTAs of pharmaceuticals.

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.

Cost-effectiveness of oral triptans for acute migraine: mixed treatment comparison.

BACKGROUND: The cost-effectiveness of triptans in the treatment of migraine has not been assessed since generic sumatriptan entered the Finnish market in 2008. METHODS: Using systematic review and mixed treatment comparison, the effectiveness of triptans was estimated with regard to 2-hour response, 2-hour pain-free, recurrence, and any adverse event, using published clinical data. Direct and indirect costs (2010 EUR, societal perspective) and quality-adjusted life-years (QALYs) were evaluated over one acute migraine attack using a decision-tree model. RESULTS: The meta-analysis combined data from fifty-six publications. The highest probability of achieving the primary outcome, "sustained pain-free, no adverse event" (SNAE), was estimated for eletriptan 40 mg (20.9 percent). Sumatriptan 100 mg was the treatment with lowest estimated costs (€20.86), and the incremental cost-effectiveness ratio of eletriptan 40 mg compared with sumatriptan 100 mg was €43.65 per SNAE gained (€19,659 per QALY gained). CONCLUSION: Depending on the decision-maker's willingness-to-pay threshold, either sumatriptan 100 mg or eletriptan 40 mg is likely to be cost-effective.

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.

[Indirect comparison and network meta-analyses--new tools for the assessment of evidence on the relative efficacy of drugs]. / Epäsuora vertailu ja verkostometa-analyysit --uudet työkalut lääkkeiden suhteellisen tehon ja vaikuttavuuden arviointiin.

Meta-analysis allows the quantitative combination of results of multiple studies that address similar research questions. Traditional meta-analysis of studies involving a direct comparison of two treatment alternatives can be applied to estimate the overall relative efficacy of these two treatment alternatives. All treatment options relevant to practical treatment decisions are, however, not always compared directly against each other in clinical studies, but indirect comparison via a common comparator may be possible. To use all relevant evidence from both direct and indirect comparisons of treatment options, advanced methods of meta-analysis have been developed. These so-called network meta-analyses extend the traditional meta-analysis to cases where a network of studies enables different pair-wise direct and indirect comparisons between multiple treatment alternatives, thereby forming a network of relevant evidence.

Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men.

OBJECTIVE: This study evaluated the long-term cost-effectiveness of atorvastatin 20 mg, rosuvastatin 10 mg and simvastatin 40 mg in primary and secondary prevention of CHD in Finland. RESEARCH DESIGN AND METHODS: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3-6.6% baseline risk of dying from cardiovascular disease within a 10-year period. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (euro/LYG) and cost of quality adjusted life years gained (euro/QALY). RESULTS: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was euro10 834 and the cost of one QALY gained was euro36 548 (discount rate 5% per annum). Corresponding figures for atorvastatin were euro31 286/LYG and euro105 599/QALY. CONCLUSIONS: If the decision makers' willingness to pay for a QALY gained is around euro40 000 there is a high probability (>50%) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3-6.6% risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.