A policy review of the introduction of the MenACWY vaccine in toddlers across multiple countries.

INTRODUCTION: Immunization is the best strategy to protect individuals from invasive meningococcal disease (IMD). To support decision-making around immunization, this paper considers what has led four countries and regions of two more to introduce the quadrivalent MenACWY vaccine in toddlers (ages 12-24 months). AREAS COVERED: A narrative literature review was conducted to identify countries that have introduced a MenACWY vaccination program for toddlers. Information from peer-reviewed publications, reports, and policy documents for each identified country was extracted. Australia, Chile, the Netherlands, Switzerland, and regions of Italy and Spain have introduced the MenACWY vaccine in their toddler programs, driven by the rising incidence of MenW and MenY and the vaccine's ability to provide protection against other serogroups. Australia and the Netherlands considered the economic impacts of implementing a MenACWY toddler vaccination program. Vaccination uptake and effects are reported for three countries; however, in two, isolating the vaccine's effect from the collateral effect of COVID-related measures is difficult. EXPERT OPINION: Increased convergence of vaccination policies and programs is needed internationally, as IMD recognizes no borders.PL AIN LANGUAGE SUMMARYVaccination is the best defense against meningitis, a deadly disease. While someone of any age can contract it, children 0-24 months of age are disproportionately affected. The increasing number of cases of meningitis has led four countries plus regions of two more to introduce into their vaccination schedules for toddlers (ages 12-24 months) a vaccine that protects against four different serogroups rather than one serogroup alone. This paper considers what has driven that shift.

Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making.

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

Health State Utilities for Acute Myeloid Leukaemia: A Time Trade-off Study.

OBJECTIVES: Acute myeloid leukaemia (AML) is an aggressive haematological cancer associated with significant humanistic impact. The current study assessed how the general public in the United Kingdom (UK) values AML health states. METHODS: The composite time trade-off (cTTO) methodology was employed to elicit health state utilities in AML. Pertinent AML literature related to symptom and quality-of-life impact including physical, functional and emotional well-being, as well as the safety profile of AML treatments, were taken into consideration for drafting health state descriptions. Ten health states included in the study were newly diagnosed AML, induction, consolidation, maintenance, long-term follow-up, relapsed/refractory, stem-cell transplant (SCT) procedure, SCT recovery, SCT long-term follow-up with complications and SCT long-term follow-up without complications. The descriptions were validated by haematologists and nurse specialists for clinical accuracy and completeness. A total of 210 individuals from the general UK population participated in the cTTO interviews. Descriptive statistics were computed for health state utility values. RESULTS: The mean age of the participants was 44.0 years (standard deviation [SD] 14.9, range 18-81) and comprised 129 (61.4%) female participants. The utility values ranged from 0.94 (SD 0.13) for SCT long-term follow-up without complications to - 0.21 (SD 0.62) for the SCT procedure. CONCLUSIONS: The study provides health utilities for a range of AML health states, with the SCT procedure health state being valued worse than death. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of AML therapies.

Economic burden associated with acute myeloid leukemia treatment.

The economic burden associated with acute myeloid leukemia (AML) is poorly defined and understudied. The goal of this study is estimate the direct cost of illness for AML in the United States (US) and the United Kingdom (UK), by conducting a comprehensive literature review and calculating the average direct cost-of-illness per patient for the first 6 months of therapy. Patients were grouped by therapy: intensive chemotherapy alone; induction chemotherapy followed by allogeneic stem cell transplantation (alloSCT); low intensity therapy; and best supportive care. Data suggest that the pathways alloSCT, followed by intensive chemotherapy, are associated with the highest direct costs. Calculated direct costs suggest that they are higher in the US ($14,014 for BSC-only to $352,682 for alloSCT) than in the UK (£3708 [$5837] for BSC-only to £112,545 [$177,187]). AML appears to be associated with significant direct economic costs, but more studies are needed to fully assess the economic impact especially in relation to total and indirect costs.

Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature.

AIMS: Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. A systematic literature review was conducted to provide an overview of published literature in the last 10-years on the epidemiology, humanistic burden and economic burden of PDPN in Europe. METHODS: A search was performed according to pre-defined strategy and review criteria in Embase, Pubmed, and conference proceedings databases from 2003 till December 2012. In total, 30 publications written in English covering the relevant patient population and topics of interest. RESULTS: European prevalence ranges from 6% to 34% in diabetes mellitus patients. PDPN has a significant humanistic and economic impact. Patients are limited in their general functioning and their ability to sleep and often experience anxiety and depression. Not surprisingly, PDPN is associated with reduced Health-Related-Quality-of-Life (HRQoL). PDPN patients incur high health care costs due to hospitalizations and outpatient visits. In addition, the painful symptoms cause impaired work productivity. Studies suggest both humanistic and economic burden increase with higher pain severity. CONCLUSIONS: The burden from PDPN appears to be higher with increasing pain severity. More severe pain leads to a higher impairment in daily functioning, sleep and HRQoL. Higher pain intensity also leads to increasing healthcare costs and work productivity losses.

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges.

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2(nd) generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.

Cost effectiveness of long-acting risperidone in Sweden.

BACKGROUND: In Sweden, risperidone long-acting injectable (RLAI) is generally used in a population of schizophrenia patients who are at a high risk of being non-compliant. However, RLAI might also be suitable for use in the general schizophrenia population. OBJECTIVES: To analyse the clinical and economic effects of RLAI in the Swedish treatment practice using a discrete-event simulation (DES) model. Treatment outcomes and direct costs were analysed for both the high-risk non-compliant patient population and the general schizophrenia population. METHODS: An existing DES model was adapted to simulate the treatment of schizophrenia in Sweden. Model inputs were based on literature research and supplemented with expert opinion. In the high-risk non-compliant schizophrenia population, RLAI was compared with haloperidol LAI. The analysis was built upon differences in symptom reduction, time between relapses, compliance and adverse effect profile between the two drugs. Main outcomes were the predicted incremental (discounted) costs (€) and effects (QALYs). In the general schizophrenia population, RLAI was compared with oral olanzapine. This analysis was built upon differences in compliance and adverse effects between the drugs. Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess the sensitivity of the results of the two analyses. RESULTS: In the high-risk non-compliant patient population, RLAI was predicted to generate 0.103 QALYs per patient over 3 years while realizing cost savings of €5013 (year 2007 values) compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI was the difference in Positive and Negative Syndrome Scale (PANSS) reduction between the two drugs, followed by the difference in adverse effects. The PSA showed that, in this setting, RLAI had a probability of 100% of being cost effective at a willingness-to-pay (WTP) threshold of €43,300 per QALY gained, compared with haloperidol LAI. The probability that RLAI combines additional effectiveness with cost savings compared with haloperidol LAI was estimated at 94%. When analysing RLAI in the general schizophrenia population, it was predicted to generate 0.043 QALYs and save €239 per patient over 5 years compared with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI in this scenario. In the PSA it was shown that RLAI had a probability of 78% of being cost effective at a WTP threshold of €43,300 per QALY gained, compared with olanzapine. The estimated probability that RLAI combines additional effectiveness with cost savings was 50% and the probability that RLAI is less effective and more costly than olanzapine was negligible (0.2%). CONCLUSIONS: Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.