Some reflections on the use of inappropriate comparators in CEA.

Although the choice of the comparator is one of the aspects with a highest effect on the results of cost-effectiveness analyses, it is one of the less debated issues in international methodological guidelines. The inclusion of an inappropriate comparator may introduce biases on the outcomes and the recommendations of an economic analysis. Although the rules for cost-effectiveness analyses of sets of mutually exclusive alternatives have been widely described in the literature, in practice, they are hardly ever applied. In addition, there are many cases where the efficiency of the standard of care has never been assessed; or where the standard of care has demonstrated to be cost-effective with respect to a non-efficient option. In all these cases the comparator may lie outside the efficiency frontier, so the result of the CEA may be biased. Through some hypothetical examples, the paper shows how the complementary use of an independent reference may help to identify potential inappropriate comparators and inefficient use of resources.

Costs and quality of life in community-dwelling patients with Alzheimer's disease in Spain: results from the GERAS II observational study.

BACKGROUND: Country-specific data on resource use and costs associated with Alzheimer's disease (AD) help inform governments about the increasing need for medical and financial support as the disease increases in prevalence. METHODS: GERAS II, a prospective observational study, assessed resource use, costs, and health-related quality of life (HRQoL) among patients with AD and their caregivers in Spain. Community-dwelling patients aged ≥55 years with probable AD, and their primary caregivers, were recruited by study investigators during routine clinical practice and assessed as having mild, moderate, or moderately severe/severe (MS/S) AD dementia based on patient Mini-Mental State Examination scores. Costs of AD were calculated by applying costs to resource-use data obtained in caregiver interviews using the Resource Utilization in Dementia instrument. Total societal costs included patients' health and social care costs and caregiver informal care costs. Baseline results are presented. RESULTS: Total mean monthly societal costs/patient (2013 values) were €1514 for mild (n = 116), €2082 for moderate (n = 118), and €2818 for MS/S AD dementia (n = 146) (p value <0.001 between groups). Caregiver informal care costs comprised most of the total societal costs and differed significantly between groups (€1050, €1239, €1580, respectively; p value = 0.013), whereas patient healthcare costs did not. Across AD dementia severity groups, patient HRQoL (measured by proxy) decreased significantly (p value <0.001), caregiver subjective burden significantly increased (p value <0.001) and caregiver HRQoL was similar. CONCLUSIONS: Societal costs associated with AD in Spain were largely attributable to caregiver informal care costs and increased with increasing AD dementia severity.

Cost-Effectiveness of Florbetapir-PET in Alzheimer's Disease: A Spanish Societal Perspective.

BACKGROUND: The rising prevalence of Alzheimer's disease (AD), and other diseases associated with dementia, imposes significant burden to various stakeholders who care for the elderly. Management of AD is complicated by multiple factors including disease-specific features which make it difficult to diagnose accurately during milder stages. Florbetapir F18 positron emission tomography (florbetapir-PET) is an approved imaging tool used to capture beta-amyloid neuritic plaque density in brains of cognitively impaired adults undergoing evaluation for AD and other causes of cognitive impairment. It has the potential to help improve healthcare outcomes as it may help clinicians identify patients with AD early so that treatments are initiated when most effective. AIMS OF THE STUDY: Evaluate the potential long-term clinical and economic outcomes of adopting florbetapir-PET--adjunctive to standard clinical evaluation (SCE)--versus SCE alone in the diagnostic assessment of cognitively impaired patients with suspected AD. METHODS: A decision analysis with a ten-year time horizon was developed in compliance with Good Research Practices and CHEERS guidelines. The target population was comprised of Spanish patients who were undergoing initial assessment for cognitive impairment (Mini-Mental State Examination [MMSE] score=20). Diagnostic accuracy, rate of cognitive decline, effect of drugs on cognition and dwelling status, economic burden (direct and indirect costs), and quality of life (QoL) were based on relevant clinical studies and published literature. Scenario analysis was applied to explore outcomes under different conditions, which included: (i) use of florbetapir-PET earlier in disease progression (MMSE score=22); and (ii) the addition of fluorodeoxyglucose (FDG)-PET to SCE. RESULTS: Adjunctive florbetapir-PET increased quality-adjusted life years (QALYs) by 0.008 years and increased costs by 36 compared to SCE alone (incremental cost-effectiveness ratio [ICER], 4,769). Use of florbetapir-PET was dominant in alternate scenarios. Sensitivity analyses indicated rates of institutionalization (by MMSE) and MMSE score upon initiation of acetylcholinesterase inhibitor (AChEI) treatment most influenced the primary outcome (ICER) in the base case scenario. Over 82% of probabilistic simulations were cost-effective using the Spanish threshold (30,000/QALY). DISCUSSION: The addition of florbetapir-PET to SCE is expected to improve the accuracy of AD diagnoses for patients experiencing cognitive impairment; it is cost-effective due to decreased healthcare costs and caregiver burden. Prospective studies of the clinical utility of florbetapir-PET are necessary to evaluate the long-term implications of adopting florbetapir-PET on clinical outcomes and costs in real-world settings. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Florbetapir-PET is expected to improve decision-making regarding appropriate and sufficient care for cognitively impaired patients with suspected AD, while cost-effective. IMPLICATIONS FOR HEALTH POLICIES: Earlier and more accurate diagnosis of AD may help to improve patient's health status and reduce treatment costs by effectively allocating healthcare resources and maximizing the benefit of treatments and supportive services. IMPLICATIONS FOR FURTHER RESEARCH: Use of florbetapir-PET may help accurately identify patients with AD. The development of novel therapeutics for use with companion diagnostics may provide additional benefits by slowing or halting progressive cognitive decline with AD, increase QoL and prolong survival.

Long-acting olanzapine versus long-acting risperidone for schizophrenia in Spain - a cost-effectiveness comparison.

BACKGROUND: In schizophrenia, medication adherence is critical to achieve better patient outcomes and to avoid relapses, which are responsible for a significant proportion of total healthcare costs for this chronic illness. The aim of this study was to assess the cost-effectiveness of olanzapine long-acting injection (OLAI) compared with risperidone long-acting injection (RLAI) in patients with schizophrenia in Spain. METHODS: A discrete event simulation (DES) model was developed from a Spanish healthcare system perspective to estimate clinical and economic outcomes for patients with schizophrenia over a five-year period. Patients who had earlier responded to oral medication and have a history of relapse due to adherence problems were considered. Identical model populations were treated with either OLAI or RLAI. In the absence of a head-to-head clinical trial, discontinuation and relapse rates were obtained from open-label studies. The model accounted for age, gender, risks of relapse and discontinuation, relapse management, hospitalization, treatment switching and adverse events. Direct medical costs for the year 2011 and outcomes including relapse avoided, life years (LYs), and quality-adjusted life years (QALYs) were discounted at a rate of 3%. RESULTS: When comparing RLAI and OLAI, the model predicts that OLAI would decrease 5-year costs by €2,940 (Standard Deviation between replications 300.83), and result in a QALY and LY gains of 0.07 (SD 0.019) and 0.04 (SD 0.025), respectively. Patients on OLAI had fewer relapses compared to RLAI (1.392 [SD 0.035] vs. 1.815 [SD 0.035]) and fewer discontinuations (1.222 [SD 0.031] vs. 1.710 [SD 0.039]). Sensitivity analysis indicated that the study was robust and conclusions were largely unaffected by changes in a wide range of parameters. CONCLUSIONS: The present evaluation results in OLAI being dominant over RLAI, meaning that OLAI represents a more effective and less costly alternative compared to RLAI in the treatment of patients with schizophrenia in the Spanish setting.

Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population.

BACKGROUND: The objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) for patients with predominantly non-squamous histology in the Spanish healthcare setting. METHODS: A Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared with docetaxel. Costs were collected from the Spanish healthcare perspective. RESULTS: Outcomes of the model included total costs, total quality-adjusted life years (QALYs), total life years gained (LYG) and total progression-free survival (PFS). Mean survival was 1.03 years for the pemetrexed arm and 0.89 years in the docetaxel arm; QALYs were 0.52 compared to 0.42. Per-patient lifetime costs were 34677 euros and 32343 euros, respectively. Incremental cost-effectiveness ratios were 23967 euros per QALY gained and 17225 euros per LYG. CONCLUSIONS: Pemetrexed as a second-line treatment option for patients with a predominantly non-squamous histology in NSCLC is a cost-effective alternative to docetaxel according to the 30000 euros /QALY threshold commonly accepted in Spain.

Health economics: the start of clinical freedom.

BACKGROUND: Since Professor Hampton announced the death of clinical freedom in 1983, the increasing influence of Evidence-based Medicine and Health Technology Assessment has contributed to augment the feeling that clinicians have a secondary role in the therapeutic decision-making process. DISCUSSION: This article constitutes a reflection on how clinicians may use the results of economic evaluations in their daily clinical practice, making decisions about cost-effectiveness on a case by case basis, and addressing both the patient's and society's needs. To that end, some illustrating examples are taken from the literature to show there are factors with great impact on cost-effectiveness results that can be easily identified and modified by clinicians. SUMMARY: The evolution of the discipline and the trend towards a tailored therapy suggest that health economics is not the end of clinical freedom but the start of it.

Cost-effectiveness analysis of ixekizumab versus secukinumab in patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis in Spain.

OBJECTIVE: To conduct a cost-effectiveness analysis from the perspective of the Spanish National Health System (NHS) comparing ixekizumab versus secukinumab. DESIGN: A Markov model with a lifetime horizon and monthly cycles was developed based on the York model. Four health states were included: a biological disease-modifying antirheumatic drug (bDMARD) induction period of 12 or 16 weeks, maintenance therapy, best supportive care (BSC) and death. Treatment response was assessed based on both Psoriatic Arthritis Response Criteria (PsARC) and ≥90% improvement in the Psoriasis Area Severity Index score (PASI90). At the end of the induction period, responders transitioned to maintenance therapy. Non-responders and patients who discontinued maintenance therapy transitioned to BSC. Clinical efficacy data were derived from a network meta-analysis. Health utilities were generated by applying a regression analysis to Psoriasis Area Severity Index and Health Assessment Questionnaire‒Disability Index scores collected in the ixekizumab SPIRIT studies. Results were subject to extensive sensitivity and scenario analysis. SETTING: Spanish NHS. PARTICIPANTS: A hypothetical cohort of bDMARD-naïve patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis was modelled. INTERVENTIONS: Ixekizumab and secukinumab. RESULTS: Ixekizumab performed favourably over secukinumab in the base-case analysis, although cost savings and quality-adjusted life-year (QALY) gains were modest. Total costs were €153 901 compared with €156 559 for secukinumab (difference -€2658). Total QALYs were 9.175 vs 9.082 (difference 0.093). Base-case results were most sensitive to the annual bDMARD discontinuation rate and the modification of PsARC and PASI90 response to ixekizumab or secukinumab. CONCLUSION: Ixekizumab provided more QALYs at a lower cost than secukinumab, with differences being on a relatively small scale. Sensitivity analysis showed that base-case results were generally robust to changes in most input parameters. TRIAL REGISTRATION NUMBER: SPIRIT-P1: NCT01695239; Post-results, SPIRIT-P2: NCT02349295; Post-results.

Resource use and costs in patients with poorly controlled type 2 diabetes mellitus and obesity in routine clinical practice in Spain.

OBJECTIVE: To compare healthcare resource use (HRU) and annual costs in type 2 diabetes mellitus (T2DM) patients with poor glycaemic control and obesity versus good glycaemic control without obesity. METHODS: Observational retrospective study based on the analysis of electronic medical records from the BIG-PAC database, with one year of follow-up. T2DM patients aged ≥30 years who requested medical care during 2013 were included. Annual HRU and costs per patient were compared between a reference group (HbA1c ≥ 8%, BMI ≥30 kg/m2, receiving ≥2 oral antidiabetic drugs [OADs]) and a control group (HbA1c < 7% and BMI <30 kg/m2). Direct and indirect costs (lost productivity) were analysed. Cost comparisons across groups were made using the analysis of covariance (ANCOVA) for each cost component, with age, sex, time from diagnosis, Charlson comorbidity index, OAD number and sex by group interaction as covariates. RESULTS: During the follow-up, patients in the reference group (N = 2709) had a greater HRU than those in the control group (N = 5266), especially in the number of primary care (PC) visits (11.8 vs. 9.8; 95%CI: 11.5-12.1 vs. 9.6-10.0) and days of hospitalization (1.1 vs 0.6; 95%CI: 1.0-1.2 vs. 0.5-0.7). The main components of the total cost were hospital admissions (24.5%), productivity losses (16.3%), complementary tests (14.4%), PC visits (14.2%) and medication (13.6%) in the reference group and medication (19.6%), hospital admissions (18.7%) and PC visits (18.2%) in the control group. The corrected mean annual cost per patient was higher in the reference than in the control group: €1804 vs. €1309; p < .001. CONCLUSIONS: Poor glycaemic control and obesity in T2DM patients were associated with increased HRU and costs in routine clinical practice.

Patient-physician discrepancy in the perception of immune-mediated inflammatory diseases: rheumatoid arthritis, psoriatic arthritis and psoriasis. A qualitative systematic review of the literature.

INTRODUCTION: Recommendations on chronic diseases management emphasise the need to consider patient perspectives and shared decision-making. Discrepancies between patients and physicians' perspectives on treatment objectives, disease activity, preferences and treatment have been described for immune-mediate inflammatory diseases. These differences could result on patient dissatisfaction and negatively affect outcomes. OBJECTIVE: To describe the degree of patient-physician discrepancy in three chronic immune-mediated inflammatory diseases (rheumatoid arthritis [RA], psoriatic arthritis [PsA] and psoriasis [Ps]), identifying the main areas of discrepancy and possible predictor factors. METHODS: Qualitative systematic review of the available literature on patient and physician discrepancies in the management of RA, PsA and Ps. The search was performed in international (Medline/PubMed, Cochrane Library, ISI-WOK) and Spanish electronic databases (MEDES, IBECS), including papers published from April 1, 2008 to April 1, 2018, in English or Spanish, and conducted in European or North American populations. Study quality was assessed by the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: A total of 21 studies were included (13 RA; 3 PsA; 4 Ps; 1 RA, Ps, and Axial Spondyloarthritis). A significant and heterogeneous degree of discrepancy between patients and physicians was found, regarding disease activity, treatment, clinical expectations, remission concept, and patient-physician relationship. In RA and PsA, studies were mainly focused on the evaluation of disease activity, which is perceived as higher from the patient's than the physician's perspective, with the discrepancy determined by factors such as patient's perception of pain and fatigue. In Ps, studies were focused on treatment satisfaction and patient-physician relationship, showing a lower degree of discrepancy in the satisfaction regarding these aspects. CONCLUSIONS: There is a significant degree of patient-physician discrepancy regarding the management of RA, PA, and Ps, what can have a major impact on shared decision-making. Future research may help to show whether interventions considering discrepancy improve shared decision-making.

Clinical Inertia in Poorly Controlled Type 2 Diabetes Mellitus Patients with Obesity: An Observational Retrospective Study.

INTRODUCTION: To evaluate clinical inertia in patients with type 2 diabetes mellitus (T2DM), obesity and poor glycaemic control in routine clinical practice. METHODS: This was a retrospective, observational study based on the analysis of medical records from the BIG-PAC® database. Subjects who required medical care in 2013 with the following characteristics were enrolled in the study: age ≥ 30 years, diagnosis of T2DM, glycosylated haemoglobin (HbA1c) ≥ 8%, obesity (body mass index [BMI] ≥ 30 kg/m2) and treatment with ≥ 2 oral antidiabetic drugs (OADs). Inertia was evaluated by time (days) to the first intensification during the period while HbA1c levels were ≥ 8% and percentage of patients whose treatment was not intensified at 6 months, 1, 2 and 3 years and the end of follow-up. The minimum length of follow-up was 4 years. Descriptive analyses and Kaplan-Meier survival curves were performed. RESULTS: A total of 13,824 patients with T2DM receiving ≥ 2 OADs were identified; of these 2709 (19.6%) had HbA1c ≥ 8% and BMI ≥ 30 kg/m2, thus fulfilling the inclusion criteria. Of these 2709 patients, the mean age was 65.5 (standard deviation [SD] 12.0) years; 54.9% were male, mean HbA1c level was 9.2% (SD 1.3%); mean BMI was 32.1 (SD 0.9) kg/m2; and mean time from diagnosis was 8.2 (SD 3.0) years. HbA1c remained ≥ 8% for a median of 440 (95% confidence interval [CI] 421-459) days. The median time to first intensification was 456 (95% CI 429-483) days. No intensification had occurred in 77.8, 59.5, 41.5, 28.1 and 22.4% of patients at 6 months, 1, 2, 3 years and the end of follow-up, respectively. CONCLUSIONS: The patients with T2DM analysed in this study had a mean HbA1c of 9.2% at baseline, and this remained at ≥ 8% for > 1 year. The time to the first treatment intensification was longer than that recommended by guidelines. Treatment was not intensified in a large percentage of patients, with almost 60% of patients not receiving intensification at 1 year of follow-up.

Patient Decision Aid (PDA) for Patients with Rheumatoid Arthritis Reduces Decisional Conflict and Improves Readiness for Treatment Decision Making.

OBJECTIVES: The aim of this study was to develop and assess the effectiveness of a patient decision aid (PDA) to support treatment decision making in Spanish patients with moderate-to-severe rheumatoid arthritis (RA) who fail to achieve the therapeutic goal with the current disease-modifying antirheumatic treatment strategy. METHODS: The PDA was developed in accordance with the International Patient Decision Aids Standards recommendations. A steering group led the project. Three literature reviews and two focus groups were performed to develop the PDA prototype. To check its comprehensibility, acceptability, and feasibility, alpha-testing was performed using the Decision Support Acceptability Scale (DSAS). Beta-testing was conducted to assess preliminary evidence of PDA efficacy using the Decisional Conflict Scale (DCS) before and after PDA use. Readiness was evaluated using the Preparation for Decision Making Scale (PDMS). RESULTS: The PDA included (1) a brief description of RA, (2) treatment information, and (3) a values clarification section. Alpha-testing revealed that most patients considered that the information was presented in a good or excellent way and it could help clarify their values and facilitate treatment decision making. Most rheumatologists agreed that the PDA was easy to understand, to use, and allowed them to reach a shared decision. Beta-testing showed that PDA significantly reduced overall patients' decisional conflict [33.2 (DE: 21.4) vs 24.6 (23.5); p < 0.001] and prepared the patient for decision making [PDMS: 67.5 (21.0)]. CONCLUSIONS: We developed a PDA for Spanish patients with moderate-to-severe RA that reduces patients' decisional conflict and increases their readiness for decision making. The use of this PDA in routine clinical practice may improve the quality of the decision-making process and the quality of the choices made.

[What is an efficient health intervention in Spain in 2020?] / ¿Qué es una intervención sanitaria eficiente en España en 2020?

Fifteen years ago, Gaceta Sanitaria published the article entitled "What is an efficient health technology in Spain?" The growing interest in setting the price of new technologies based on the value they provide to health systems and the experience accumulated by the countries in our environment make it opportune to review what constitutes an efficient health intervention in Spain in 2020. Cost-effectiveness analysis continues to be the reference method to maximize social health outcomes with the available resources. The interpretation of its results requires establishing reference values that serve as a guide on what constitutes a reasonable value for the health care system. Efficiency thresholds must be flexible and dynamic, and they need to be updated periodically. Its application should be based on and transparency, and consider other factors that reflect social preferences. Although setting thresholds is down to political decision-makers, in Spain it could be reasonable to use thresholds of 25,000 and 60,000 Euros per QALY. However, currently, in addition to determining exact figures for the threshold, the key question is whether the Spanish National Health System is able and willing to implement a payment model based on value, towards achieving gradual financing decisions and, above all, to improve the predictability, consistency and transparency of the process.

What Matters Most to Patients and Rheumatologists? A Discrete Choice Experiment in Rheumatoid Arthritis.

INTRODUCTION: To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). METHODS: Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2-4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. RESULTS: Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. CONCLUSION: Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process.

A modelled economic evaluation comparing atomoxetine with methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder in Spain.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurobehavioural disorder, affecting 3-6% of school age children and adolescents in Spain. Methylphenidate (MPH), a mild stimulant, had long been the only approved medication available for ADHD children in Spain. Atomoxetine is a non-stimulant alternative in the treatment of ADHD with once-a-day oral dosing. This study aims to estimate the cost-effectiveness of atomoxetine compared to MPH. In addition, atomoxetine is compared to 'no medication' for patient populations who are ineligible for MPH (i.e. having stimulant-failure experience or co-morbidities precluding stimulant medication). METHODS: An economic model with Markov processes was developed to estimate the costs and benefits of atomoxetine versus either MPH or 'no medication'. The incremental cost per quality-adjusted life-year (QALY) was calculated for atomoxetine relative to the comparators. The Markov process incorporated 14 health states, representing a range of outcomes associated with treatment options. Utility values were obtained from the utility valuation survey of 83 parents of children with ADHD. The clinical data were based on a thorough review of controlled clinical trials and other clinical literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over a 1-year duration, with costs estimated from the perspective of the National Health Service in Spain. RESULTS: For stimulant-naive patients without contra-indications to stimulants, the incremental costs per QALY gained for atomoxetine were euro 34,308 (compared to an immediate-release MPH) and euro 24,310 (compared to an extended-release MPH). For those patients who have stimulant-failure experience or contra-indications to stimulants, the incremental costs per QALY gained of atomoxetine compared to 'no medication' were euro 23,820 and euro 23,323, respectively. CONCLUSION: The economic evaluation showed that atomoxetine is an effective alternative across a range of ADHD populations and offers value-for money in the treatment of ADHD.

Observational studies with type 2 diabetes mellitus treatments in Spain: A systematic literature review.

The aim of this systematic literature review (SLR) was to provide an overview of the Spanish research landscape of observational studies conducted with antidiabetic drugs in T2DM patients, published in the last five years, with special focus on the objectives, methodology and main research areas. Twenty-two articles, corresponding to 20 studies, were included in the analysis. Around 82% of the studies employed a longitudinal study design, collected data retrospectively (72.7%), and were based on secondary data use (63.6%). Pharmacotherapeutical groups most frequently studied were insulin (31.8%) and DPP4i (13.6%). Analytic design was employed most in the studies (68.2%), followed by descriptive analysis (22.7%). In the top five of the most studied variables are those related to effectiveness assessed according to glycaemic control (91%), treatment patterns (82%), safety (hypoglycaemia) (59%), the identification of effectiveness predictive factors (45%) and effectiveness according to other control measures such as anthropometric control or cardiovascular risk factors (36%).

Epidemiology, Quality of Life, and Costs Associated with Hypoglycemia in Patients with Diabetes in Spain: A Systematic Literature Review.

OBJECTIVE: To assess the burden of hypoglycemia in patients with diabetes mellitus (DM) in Spain, including epidemiological data and information relating to healthcare resource utilization (HRU) and costs, and patients' quality of life (QoL). METHODS: A systematic literature review (SLR) was conducted to identify studies that included original information on epidemiology, HRU and costs, and/or QoL associated with hypoglycemia in patients with DM in Spain, published in either Spanish or English, between January 2007 and April 2017. RESULTS: Fifteen articles, involving 14 studies, were identified in the SLR and included in the analysis. The estimated rate of severe hypoglycemia (SH) events per patient per year ranged from 0.90 to 1.50 in patients with type 1 DM (T1DM) and from 0.30 to 0.63 in patients with type 2 DM (T2DM). The data on HRU differed extensively between studies, making it difficult to draw a conclusion. Total costs per SH event ranged from €409.97 in patients with T1DM to €713.10 in patients with DM. Work absence was reported in 11.80-18% of the working patients. Further, patients who experienced hypoglycemic events expressed a higher fear and had a poorer QoL than those who did not report these events. CONCLUSION: Although the data included in the SLR were difficult to synthesize due to heterogeneity of the study designs and patient characteristics in the 14 studies, our search identified a high burden associated with hypoglycemic events in terms of HRU and costs, and patients' QoL. Further research is recommended to reach a consensus on hypoglycemia definition and study design to provide robust evidence on the burden of hypoglycemia and to accurately weigh the impact of this acute complication in Spain. FUNDING: Eli Lilly and Company.

Cost-effectiveness analysis of baricitinib versus adalimumab for the treatment of moderate-to-severe rheumatoid arthritis in Spain.

Background: Baricitinib is an oral janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and is approved in Europe for use in adults with moderately-to-severely active RA and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy. To date, no economic evaluations have assessed the cost-effectiveness of baricitinib in the Spanish setting. Objectives: To evaluate the cost-effectiveness of baricitinib versus adalimumab for the treatment of moderately-to-severely active RA in the Spanish setting. Methods: A discrete event simulation model was developed in Microsoft Excel. Costs and outcomes were estimated over a lifetime horizon using the Spanish national payer perspective. The model compared baricitinib 4 mg once daily in combination with methotrexate with adalimumab 40 mg every other week in combination with methotrexate. Effectiveness and physical function were captured using the American College of Rheumatology criteria and the Health Assessment Questionnaire-Disability Index, input values of which were derived from a phase 3, double-blind, placebo- and active-controlled trial (RA-BEAM; funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358). Costs are presented in Euros, 2018 values. Results: In the base case analysis, baricitinib was associated with a quality-adjusted life year gain of 0.09 years over a lifetime horizon, at an incremental cost of -€558 versus adalimumab. Results of various scenario analyses and probabilistic sensitivity analysis generally were consistent with the base case analysis. Conclusion: This analysis suggests that baricitinib is a cost-effective treatment option compared to adalimumab for Spanish patients with moderately-to-severely active RA and a previous inadequate response or intolerance to csDMARD therapy.

Health-related quality of life in type 1 diabetes mellitus pediatric patients and their caregivers in Spain: an observational cross-sectional study.

Objectives: This study assessed the health-related quality of life (HRQOL) of pediatric patients with type 1 diabetes mellitus (T1DM) and their caregivers.Methods: CHRYSTAL was an observational cross-sectional study conducted in Spain in 2014 on 275 patients under 18 years old diagnosed with T1DM. Patient/caregiver pairs were stratified by patients' HbA1c level (≥7.5% versus <7.5%) and by presence or absence of T1DM complications and/or comorbidities. EQ-5D and PedsQL questionnaires were administered to patients and caregivers.Results: On the EQ-5D, according to caregivers' perception, 17.7% of children experienced moderate pain or discomfort, 9.7% suffered problems performing usual activities, and 13.2% demonstrated moderate anxiety or depression. Mean EQ-5D index score was 0.95 and mean visual analog scale (VAS) score was 86.1. By HbA1c level (≥7.5% versus <7.5%), mean index scores were 0.94 and 0.95, and mean VAS scores were 82.8 and 89.2, respectively. Mean index scores were 0.91 for children with complications and/or comorbidities and 0.96 for children without. Mean VAS scores were 83.7 and 87.2, respectively. HRQOL per the PedsQL tool ranged from 68.1 (ages 2-4) to 73.1 (ages 13-18). EQ-5D index and VAS scores were significantly correlated (rho = 0.29-0.43) with several age groups of the PedsQL. EQ-5D scales showed significant moderate correlation between EQ-5D-Y and EQ-5D-3L proxy VAS score (rho = 0.45; p < .001).Conclusions: Patients with few complications and controlled HbA1c reported a relatively high HRQOL. The results suggest that parent-proxy EQ-5D ratings are valid for use as part of an overall health outcomes assessment in clinical studies of T1DM in pediatric patients.

Cost effectiveness of ixekizumab versus secukinumab in the treatment of moderate-to-severe plaque psoriasis in Spain.

BACKGROUND: Currently, several biologic agents are available for the treatment of moderate-to-severe plaque psoriasis, including newer agents with similar mechanisms of action and efficacy; therefore, there is a need to evaluate their efficiency in terms of cost effectiveness. OBJECTIVE: This study evaluates the cost effectiveness of recently approved interleukin (IL)-17A antagonists, ixekizumab and secukinumab, for the treatment of moderate-to-severe plaque psoriasis from the perspective of the Spanish National Health System (NHS). MATERIALS AND METHODS: A Markov model with a lifetime horizon was developed to compare the cost effectiveness of ixekizumab vs. secukinumab in a hypothetical cohort of patients with moderate-to-severe plaque psoriasis. The model used monthly cycles and included four health states: a 12-week induction period, treatment maintenance, best supportive care (BSC), and death. Patients meeting response criteria at the end of the induction period transitioned to maintenance therapy, whereas non-responders transitioned to BSC. It was assumed that, each year, 20% of patients receiving maintenance therapy would discontinue treatment. The model incorporated data from various sources, including published literature, a network meta-analysis, and expert opinion for some variables. RESULTS: Ixekizumab was dominant over secukinumab in that it gained 0.037 more quality-adjusted life years (QALYs) and saved €1951 in total costs over the lifetime horizon. Probabilistic sensitivity analysis showed a 96.6% likelihood that ixekizumab would be cost effective at a threshold of €30,000 per QALY gained. CONCLUSION: For the treatment of moderate-to-severe plaque psoriasis in Spain, ixekizumab provided additional QALYs and potential savings for the Spanish NHS compared with secukinumab. Since the magnitude of the differences in costs and QALYs was modest, other factors such as patient preferences (eg, for number of injections) and long-term safety (eg, related to time on the market) may also be important for guiding clinical decisions.