Applying reflective multicriteria decision analysis to understand the value of therapeutic alternatives in the management of gestational and peripartum anaemia in Spain.

BACKGROUND: The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain. METHODS: Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB). RESULTS: The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1. CONCLUSIONS: In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.

Social preferences for health states associated with acute myeloid leukemia for patients undergoing treatment in the United Kingdom.

BACKGROUND: Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. METHODS: This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population. A panel of UK hematologists with AML experience validated the clinical relevance and accuracy of the HSs. During the second stage, validated HSs were valued in an elicitation survey with a representative UK population sample using the time trade-off (TTO) method. Descriptive statistics and bivariate tests were obtained and performed. RESULTS: A total of eight HSs were developed and clinically validated, including treatment with chemotherapy, consolidation therapy, transplant, graft-vs-host disease (GvHD), remission, relapse, refractory, and functionally cured. In total, 125 adults participated (mean age, 49.6 years [range, 18-87 years], 52.8% female). Mean (95% confidence interval [CI]) TTO preference values (n = 120), ranked from lowest (worst HS) to highest (best HS) were as follows: refractory - 0.11 (- 0.21 to - 0.01), relapse 0.10 (0.00-0.20), transplant 0.28 (0.20-0.37), treatment with chemotherapy 0.36 (0.28-0.43), GvHD 0.43 (0.36-0.50), consolidation 0.46 (0.40-0.53), remission 0.62 (0.57-0.67), and functionally cured 0.76 (0.72-0.79). Mean (95% CI) visual analog scale preference values followed the same rank order, ranging from 0.15 (0.13-0.17) for refractory to 0.71 (0.68-0.73) for functionally cured. CONCLUSIONS: To our knowledge, this is the first study to report utility values for AML from the UK societal perspective. Participants were able to distinguish differences in severity among AML HSs, and preference values were consistent with clinical perception of HS severity. HS preference values observed in this study may be useful in future evaluations of treatment benefit, including cost-effectiveness analyses and improved patient well-being.

Psychometric properties of the incontinence utility index among patients with idiopathic overactive bladder: data from two multicenter, double-blind, randomized, Phase 3, placebo-controlled clinical trials.

BACKGROUND: Overactive bladder is a prevalent and burdensome condition. Generic utility measures may fail to reflect its full impact on patients' health status. The Incontinence Utility Index (IUI) is a community-based preference index derived from the Incontinence Quality of Life Questionnaire (I-QOL) developed to value health states related to urinary symptoms in patients with neurogenic detrusor overactivity. This study assessed the measurement properties of the IUI in patients with idiopathic overactive bladder (OAB). METHODS: Data were used from two clinical trials which recruited patients with OAB whose symptoms were inadequately managed with ≥ 1 anticholinergic medication. Psychometric evaluation included: Differential Item Functioning (DIF) analysis, concordance between I-QOL and IUI (Intraclass correlation coefficient [ICC], criterion and convergent validity according to relevant patient reported outcomes and clinical variables (Spearman's correlation coefficient, rho), responsiveness, and agreement between utility measures (ICC and Bland-Altman method). RESULTS: A total of 1,105 idiopathic OAB patients were included. Mean age (range) was 60.4 years (18-90), 87.8% (n = 970) were female. DIF was identified in 3 items, none of which are contained in the IUI. ICC (CI95%) was 0.944 (0.936-0.950). Statistically significant differences (p < 0.001) were found in IUI scores for patients improving according to the Treatment Benefit Scale (TBS). Moderate to strong correlations (rho > |0.6|) were found in the expected direction with daily incontinence, urgency episodes and disease-specific domains of King's Health Questionnaire (KHQ). Low to moderate correlations (rho:<|0.6|) were found with Short Form version 2 (SF-12v2) summary components. A large effect size was found for patients reporting improvement (0.98-1.21) or great improvement (1.87-2.56) in the TBS, as well as in patients responding to treatment (1.19-2.40). Across utility measures, directional trends were consistent with OAB symptom profile, however, a lack of agreement in absolute values was observed. CONCLUSIONS: The IUI presents good psychometric properties for valuing the impact of UI-related problems in idiopathic OAB patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00910845 and NCT00910520.

Development of the Incontinence Utility Index: estimating population-based utilities associated with urinary problems from the Incontinence Quality of Life Questionnaire and Neurogenic Module.

BACKGROUND: Generic utility instruments may not fully capture the impact and consequences of urinary problems. Condition-specific preference-based measures, developed from previously validated disease-specific patient-reported outcomes instruments, may add relevant information for economic evaluations. The aim of this study was to develop a condition-specific preference-based measure, the Incontinence Utility Index (IUI), for valuing health states associated with urinary problems. METHODS: A two-step process was implemented. First, an abbreviated health state classification system was developed from the Incontinence Quality of Life Questionnaire (I-QOL) and Neurogenic Module by applying Rasch modelling, classical psychometrical testing and expert criteria to data from two pivotal trials comprised of neurogenic detrusor overactivity (NDO) patients. Criterion, convergent validity and concordance with the original instrument was assessed in the abbreviated version. Then, a multi-attribute utility function (MAUF) was estimated from a representative sample of the UK non-institutionalized adult general population. Visual analogue and time-trade off (TTO) evaluations were applied in the elicitation process. Predictive validity of the MAUF was tested comparing estimated and direct utility scores. RESULTS: The abbreviated health state classification system generated from the NDO sample contained 5 attributes with 3 levels of response and had adequate psychometrical properties: significant differences in scores according to the reduction in the frequency of urinary incontinence episodes [UIE] (p < 0.001); Spearman correlation coefficient with number of daily UIE = -0.43; p < 0.01 and Intraclass Correlation Coefficient (ICC, 95% CI) with the original version = 0.90 (0.89-0.91; p < 0.001). Next, 442 participants were interviewed (398 cases were valid, generating 2,388 TTO evaluations) to estimate the social preferences for derived health states. Mean age was 44.75 years (interquartile range 33.5-55.5) and 60.1% were female. An overall algorithm for the IUI was estimated and transformed onto a dead = 0.00 and full health = 1.00 scale. Model fits were acceptable (R-squared = 0.923 and 0.978). Predictive validity was adequate: ICC (95% CI) = 0.928 (0.648-0.985) and Mean of Absolute Differences = 0.038. CONCLUSIONS: The newly developed IUI is a preference-based measure for urinary problems related to NDO that provides general population-based utility scores with adequate predictive validity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00461292, NCT00311376.

Adaptation into Spanish of the Clinically Useful Depression Outcome Scale (CUDOS) for assessing major depressive disorder from the patient's perspective.

OBJECTIVE: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale) into Spanish and to test its psychometrical properties in a sample of patients with major depressive disorder (MDD). METHODS: A two-step cross-sectional, multicenter validation study was conducted (linguistic adaptation into Spanish and psychometric validation). The study evaluated patients attended in Primary Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Physical ­PCS- and Mental ­MCS- Component Summaries), and the CGI-S & PGI-S (Clinical Global Impression for Severity of Illness scales for clinicians and patients, respectively). Feasibility, reliability, and validity of the Spanish version were assessed. RESULTS: In the validation study, 305 MDD patients (69.5% female) with a mean age (standard deviation-SD-) of 51.75(15.53) were included. Mean completion time was 4.47(2.4) minutes. Floor or ceiling effects were found in less than 1% of the case scores. Internal consistency was adequate (Cronbach's α= 0.88). Pearson correlation coefficients with CUDOS were: -0.42 (SOFAS), 0.45 (HAMD-17), -0.22 (PCS), -0.65 (MCS); all p<0.001. The CUDOS properly discriminated among clinical severity levels (p<0.03). CONCLUSIONS: The adapted Spanish version of the CUDOS shows adequate psychometric properties as an evaluation instrument of major depression from the patient's perspective.

Atopic dermatitis: impact on quality of life and patients' attitudes toward its management.

This work studies atopic dermatitis in the following terms: impact on patients' life; patients' satisfaction and attitudes toward topical pharmacological treatment and medical recommendations (regarding hygienic and preventive strategies) and patients' and dermatologists' impressions of severity at the moment of consultation. To this end, an epidemiological, multicentre, cross-sectional study was carried out. In total, 191 dermatologists collected data from 322 patients (163 children, 159 adults). Poor agreement between specialists' and patients' criteria was found and patients with higher severity of affectation showed higher impacts on sleep/rest, emotional and school/ professional fulfillment (p<0.001). Moreover, reported compliance with pharmacological treatment and medical recommendations was high but patients' satisfaction with these recommendations was lower than with respect to pharmacological treatment. These results highlight that although reported compliance was high, there were still non-compliance attitudes and concerns about treatments that should be answered. Finally, a significant impact on patients' life was confirmed.

Cost-effectiveness analysis of timely dialysis referral after renal transplant failure in Spain.

BACKGROUND: A cost-effectiveness analysis of timely dialysis referral after renal transplant failure was undertaken from the perspective of the Public Administration. The current Spanish situation, where all the patients undergoing graft function loss are referred back to dialysis in a late manner, was compared to an ideal scenario where all the patients are timely referred. METHODS: A Markov model was developed in which six health states were defined: hemodialysis, peritoneal dialysis, kidney transplantation, late referral hemodialysis, late referral peritoneal dialysis and death. The model carried out a simulation of the progression of renal disease for a hypothetical cohort of 1,000 patients aged 40, who were observed in a lifetime temporal horizon of 45 years. In depth sensitivity analyses were performed in order to ensure the robustness of the results obtained. RESULTS: Considering a discount rate of 3 %, timely referral showed an incremental cost of 211 €, compared to late referral. This cost increase was however a consequence of the incremental survival observed. The incremental effectiveness was 0.0087 quality-adjusted life years (QALY). When comparing both scenarios, an incremental cost-effectiveness ratio of 24,390 €/QALY was obtained, meaning that timely dialysis referral might be an efficient alternative if a willingness-to-pay threshold of 45,000 €/QALY is considered. This result proved to be independent of the proportion of late referral patients observed. The acceptance probability of timely referral was 61.90 %, while late referral was acceptable in 38.10 % of the simulations. If we however restrict the analysis to those situations not involving any loss of effectiveness, the acceptance probability of timely referral was 70.10 %, increasing twofold that of late referral (29.90 %). CONCLUSIONS: Timely dialysis referral after graft function loss might be an efficient alternative in Spain, improving both patients' survival rates and health-related quality of life at an affordable cost. Spanish Public Health authorities might therefore promote the inclusion of specific recommendations for this group of patients within the existing clinical guidelines.

Cost-effectiveness analysis of the SAPIEN 3 transcatheter aortic valve implant in patients with symptomatic severe aortic stenosis.

INTRODUCTION AND OBJECTIVES: Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. METHODS: We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. RESULTS: Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. CONCLUSIONS: In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients.

Cost analysis of the Spanish renal replacement therapy programme.

BACKGROUND: A cost analysis of the Spanish Renal Replacement Therapy (RRT) programme in the year 2010, for end-stage renal disease (ESRD) patients, was performed from the perspective of the Public Administration. METHODS: The costs associated with each RRT modality [hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation (Tx)] were analysed. The Spanish ESRD incidence and prevalence figures in the year 2010 were forecasted in order to enable the calculation of an aggregate cost for each modality. Costs were mainly computed based on a review of the existing literature and of the Official Bulletins of the Spanish Autonomous Communities. Data from Oblikue Consulting eSalud health care costs database and from several Spanish public sources were also employed. RESULTS: In the year 2010, the forecasted incidence figures for HD, PD and Tx were 5409, 822 and 2317 patients, respectively. The forecasted prevalence figures were 22,582, 2420 and 24,761 patients, respectively. The average annual per-patient costs (incidence and prevalence) were €2651 and €37,968 (HD), €1808 and €25,826 (PD) and €38,313 and €6283 (Tx). Indirect costs amounted to €8929 (HD), €7429 (PD) and €5483 (Tx). The economic impact of the Spanish RRT programme on the Public Administration budget was estimated at ~€1829 million (indirect costs included): €1327 (HD), €109 (PD) and €393 (Tx) million. CONCLUSIONS: HD accounted for >70% of the aggregate costs of the Spanish RRT programme in 2010. From a costs minimization perspective, it would be preferable if the number of incident and prevalent patients in PD were increased.

Validation of a specific measure to assess health-related quality of life in patients with schizophrenia and bipolar disorder: the 'Tolerability and quality of life' (TOOL) questionnaire.

BACKGROUND: Perception of quality of life may differ depending on the perspective. The aim of the study was to assess the psychometric properties of the Spanish version of the 'TOlerability and quality Of Life' (TOOL) questionnaire, a specific self-rated instrument to evaluate the impact of side effects of antipsychotic drugs on health-related quality of life (HRQoL). The questionnaire consists of eight items answered on a four-point Likert scale. METHODS: A psychometric study was conducted with clinically stable outpatients with schizophrenia and bipolar disorder under antipsychotic treatment. The translation and cultural adaptation of the questionnaire was performed according to international standards. Internal consistency using the Cronbach α coefficient and test-retest reliability using the intraclass correlation coefficient (ICC) was used to assess the reliability of the instrument. Patients completed generic and specific measures of quality of life and clinical severity. RESULTS: A total of 238 patients were analysed, with a mean age of 42 years (SD 10.9). The mean completion time was 4.9 min (SD 4.4). Internal consistency and intraclass correlation coefficient were adequate (Cronbach α = 0.757 and ICC = 0.90). Factorial analysis showed a unidimensional structure (a single eigenvalue >1, accounting for 39.1% of variance). Significant Spearman's rank correlations between the TOOL and both generic and specific measures were found. The questionnaire was able to discriminate among the Clinical Global Impression - Severity scores (Mann-Whitney U test, P < 0.001). CONCLUSIONS: The TOOL questionnaire shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome. TOOL constitutes a valuable addition to measure the impact of adverse events of antipsychotic drugs from the patient perspective.

Validation of a computer-adaptive test to evaluate generic health-related quality of life.

BACKGROUND: Health Related Quality of Life (HRQoL) is a relevant variable in the evaluation of health outcomes. Questionnaires based on Classical Test Theory typically require a large number of items to evaluate HRQoL. Computer Adaptive Testing (CAT) can be used to reduce tests length while maintaining and, in some cases, improving accuracy. This study aimed at validating a CAT based on Item Response Theory (IRT) for evaluation of generic HRQoL: the CAT-Health instrument. METHODS: Cross-sectional study of subjects aged over 18 attending Primary Care Centres for any reason. CAT-Health was administered along with the SF-12 Health Survey. Age, gender and a checklist of chronic conditions were also collected. CAT-Health was evaluated considering: 1) feasibility: completion time and test length; 2) content range coverage, Item Exposure Rate (IER) and test precision; and 3) construct validity: differences in the CAT-Health scores according to clinical variables and correlations between both questionnaires. RESULTS: 396 subjects answered CAT-Health and SF-12, 67.2% females, mean age (SD) 48.6 (17.7) years. 36.9% did not report any chronic condition. Median completion time for CAT-Health was 81 seconds (IQ range = 59-118) and it increased with age (p < 0.001). The median number of items administered was 8 (IQ range = 6-10). Neither ceiling nor floor effects were found for the score. None of the items in the pool had an IER of 100% and it was over 5% for 27.1% of the items. Test Information Function (TIF) peaked between levels -1 and 0 of HRQoL. Statistically significant differences were observed in the CAT-Health scores according to the number and type of conditions. CONCLUSIONS: Although domain-specific CATs exist for various areas of HRQoL, CAT-Health is one of the first IRT-based CATs designed to evaluate generic HRQoL and it has proven feasible, valid and efficient, when administered to a broad sample of individuals attending primary care settings.

[Development and validation of a generic questionnaire for evaluating satisfaction in patients with chronic disease: the SAT-Q Questionnaire]. / Desarrollo y validación de un cuestionario genérico para la evaluación de la satisfacción de los pacientes crónicos: Cuestionario SAT-Q.

OBJECTIVES: To develop and validate a brief general questionnaire to assess satisfaction in patients with chronic disease. DESIGN: epidemiological, observational, multicentre cross-sectional study. LOCATION: 4 Primary Health Care Centers from the IV Health Area in the Principality of Asturias. SUBJECTS: A total of 202 patients diagnosed with chronic illness who were following a pharmacological regimen for at least one year. METHODS: An extensive literature review was conducted to create an initial item pool of 61 questions regarding patient satisfaction. Then, a forward-backward translation into Spanish was carried out. Next, both the expert (n=8) and patient (n=30) panels led to a new version of 34 items (concerning satisfaction with medication and satisfaction with health service). Finally, scale item reduction (item-total correlation and exploratory factorial analysis -EFA-) and psychometrical validation (feasibility, reliability and criterion validity) of the SAT-Q- were evaluated. Both the SAT-Q and the SF-12 (to assess patient health related quality of life) were applied. RESULTS: Item reduction analysis resulted in 18 items: general satisfaction with medication (3), adverse-events (3), oversights (2), effectiveness (3), convenience (4) and Health services (3). Internal consistency (Cronbach α) and Intraclass Correlation Coefficients were moderate-high. Moreover, significant positive correlations between SAT-Q scores and SF-12 Physical and Mental Summary Components were found (with the exception of oversights). CONCLUSIONS: A brief questionnaire for measuring satisfaction in chronic patients has been developed and preliminary validated.

A Qualitative Research for Defining Meaningful Attributes for the Treatment of Inflammatory Bowel Disease from the Patient Perspective.

INTRODUCTION: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, inflammatory bowel diseases (IBD). Each class and type of medication available for the treatment of IBD has distinct characteristics and long-term effects that a patient may consider. We present the results of qualitative research that aimed to develop a descriptive framework that outlines the most relevant disease and/or treatment attributes for IBD treatment decisions and focuses on the patient perspective. METHODS: This research employed a three-step approach: a literature review to identify a broad list of attributes, a focus group meeting including patients and clinicians to assess the relevance of the attributes, and two rounds of voting to name and define each attribute. The literature review was used to develop the initial list of attributes. Although the same attributes were defined for both UC and CD, the relative importance of each attribute to UC or CD was considered. The list of attributes was discussed and evaluated in the focus group meeting, which included eight patient representatives and nine gastroenterologists. Using feedback elicited from the focus group meeting, the research team developed a draft of the descriptive framework that grouped the attributes into domain subsets. All members of the focus group participated in two subsequent rounds of structured, online voting, which was used to refine the wording to name and define each attribute. Additionally, participants ranked all the attributes included in the descriptive framework to suggest which attributes were less relevant and could be omitted. RESULTS: Among 574 publications retrieved from the databases and registries, we identified 32 eligible publications, and an initial list of attributes was developed. This list was refined during the focus group meeting, resulting in a draft descriptive framework of attributes within subsets of domains. The final descriptive framework was developed based on structured rounds of online voting to further refine attribute names and definitions. In the final descriptive framework, a total of ten attributes were identified: abdominal pain, other disease-related pain, bowel urgency, fatigue, risk of cancer and serious infections within the next 10 years, risk of mild to moderate complications, aesthetic complications related to treatment, emotional status, sexual life, and social life and relationships. These attributes were distributed across three domains: efficacy, complications and risk, and health-related quality of life. CONCLUSIONS: Through the identification of the ten most relevant attributes that influence patient decision making for IBD treatments, we developed a descriptive framework that should be considered by physicians when discussing IBD treatment options with their patients. The results of our qualitative research may also be helpful for the development of future IBD clinical studies and quantitative research.

[Development of the CAT-Health, the first adaptive computerized test (CAT) for the evaluation health-related quality of life in Spain]. / Desarrollo del CAT-Health, primer test adaptativo informatizado para la evaluación de la calidad de vida relacionada con la salud en España.

OBJECTIVES: To develop a Computerized Adaptive Test to obtain a generic measure of the patients' perceived health state. METHODS: An experts' panel created a pool of five-alternative Likert format items, chosen among Health Related Quality of Life questionnaires validated in our country. That pool was applied to a pilot sample and later to another general sample of patients belonging to 7 Primary Health Centers in Asturias. Two response options were offered to the general sample: 1) on paper 2) on a touch panel. The Item Response Theory psychometric properties (discrimination, reliability and validity) were evaluated by means of the factorial analysis and other methods. The information function was analyzed and a study of simulation was developed. RESULTS: A pool of 140 items was created. The requirements for the application of the IRT were verified by means of the factorial analysis. A selection of items was realized following the statistical criterion and the application of the IRT. The elimination of 35 articles resulted in a test composed by 105 items. Once the questionnaire was applied to the general sample, the parameters of the items were estimated again. The parameters invariance was verified once more and other 9 items were eliminated. The result was a definitive version of 96 items. CONCLUSIONS: The Computerized Adaptive Test developed proves to be a fast and reliable tool to evaluate the Health Related Quality of Life generically. This test may imply a very important advance for the measurement of the results reported by the patients in the clinical practice.

Applying Reflective Multicriteria Decision Analysis (MCDA) to Patient-Clinician Shared Decision-Making on the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the Spanish Context.

INTRODUCTION: Unresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options. METHODS: The EVIDEM-derived framework was updated and adapted to the Spanish context. During a Chatham House session, five patients and six physicians assigned criteria weights using hierarchical point allocation and direct rating scale (alternative analysis). Informed by synthesized evidence embedded in the framework, participants scored how each criterion favored SSA treatment (reference case lanreotide) or WW and shared insights and knowledge. Weights and scores were combined into value contributions (norm. weight × score/5), which were added across criteria to derive the relative benefit-risk balance (RBRB, scale - 1 to + 1). Exploratory comparisons to US study findings were performed. RESULTS: Focusing on intervention outcomes (effectiveness, patient-reported, and safety), the mean RBRB favored treatment over WW (+ 0.32 ± 0.24), with the largest contributions from progression-free survival (+ 0.11 ± SD 0.07), fatal adverse events (+ 0.06 ± SD 0.08), and impact on HRQoL (+ 0.04 ± SD 0.04). Consideration of modulating criteria (type of benefit, need, costs, evidence, and feasibility) increased the RBRB to + 0.50 ± 0.14, with type of therapeutic benefit (+ 0.10 ± SD 0.08) and quality of evidence (+ 0.08 ± SD 0.06) contributing most towards treatment. Alternative weighting yielded similar results. Results were broadly comparable to those derived from the US study. CONCLUSION: The multicriteria framework helped Spanish patients and clinicians identify and express what matters to them. The approach is transferable across decision-making contexts. FUNDING: IPSEN Pharma.

Using a multidimensional unfolding approach to assess multiple sclerosis patient preferences for disease-modifying therapy: a pilot study.

PURPOSE: Multidimensional unfolding is a multivariate method to assess preferences using a small sample size, a geometric model locating individuals and alternatives as points in a joint space. The objective was to evaluate relapsing-remitting multiple sclerosis (RRMS) patient preferences toward key disease-modifying therapy (DMT) attributes using multidimensional unfolding. PATIENTS AND METHODS: A cross-sectional pilot study in RRMS patients was conducted. Drug attributes included relapse prevention, disease progression prevention, side-effect risk and route and schedule of administration. Assessment of preferences was performed through a five-card game. Patients were asked to value attributes from 1 (most preferred) to 5 (least preferred). RESULTS: A total of 37 patients were included; the mean age was 38.6 years, and 78.4% were female. Disease progression prevention was the most important factor (51.4%), followed by relapse prevention (40.5%). The frequency of administration had the lowest preference rating for 56.8% of patients. Finally, 19.6% valued the side-effect risk attribute as having low/very low importance. CONCLUSION: Patients' perspective for DMT attributes may provide valuable information to facilitate shared decision-making. Efficacy attributes were the most important drug characteristics for RRMS patients. Multidimensional unfolding seems to be a feasible approach to assess preferences in multiple sclerosis patients. Further elicitation studies using multidimensional unfolding with other stated choice methods are necessary to confirm these findings.

Cost-effectiveness analysis of quadrivalent influenza vaccine in Spain.

Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention.

Prevalence, Treatment, and Control of Hypercholesterolemia in High Cardiovascular Risk Patients: Evidences from a Systematic Literature Review in Spain.

INTRODUCTION: Cardiovascular diseases (CVDs) represent a major Public Health burden. High serum cholesterol levels have been linked to major CV risk. The objectives of this study were to review the epidemiology of hypercholesterolemia in high risk CV patients from Spain, by assessing its prevalence, the proportion of diagnosed patients undergoing pharmacological treatment and the degree of attained lipid control. METHODS: A systematic literature review was carried out using Medline and two Spanish databases. Manuscripts containing information on hypercholesterolemia in several high CV risk groups [diabetes mellitus (DM), Systematic COronary Risk Evaluation (SCORE) risk >5, or documented CVD], published between January 2010 and October 2014, were included. RESULTS: Of the 1947 published references initially retrieved, a full-text review was done on 264 manuscripts and 120 were finally included. Prevalence of hypercholesterolemia ranged from 50 to 84% in diabetics, 30-60% in patients with DM or elevated SCORE risk, 64-74% with coronary heart disease, 40-70% in stroke patients, and 60-80% in those with peripheral artery disease. Despite the finding that most of them were on pharmacological treatment, acceptable control of serum lipids was very variable, ranging from 15% to 65%. Among those with heterozygous familial hypercholesterolemia, 95-100% received treatment but less than 50% achieved their therapeutic goals. CONCLUSIONS: An elevated prevalence of hypercholesterolemia can be found in targeted groups at high CV risk. Although most patients are receiving pharmacological treatment, rates of lipid control continue to be low, both in primary and secondary prevention.

[Vaginal misoprostol in the prevention of postpartum hemorrhage]. / Misoprostol vaginal para la prevención de la hemorragia posparto.

OBJECTIVE: To show the advantages of the use of vaginal misoprostol, a prostaglandine E1 analogue, in the prevention of the post-partum haemorrhage. MATERIAL AND METHODS: This was a prospective, observational, comparative study. The study included 400 patients with high risk of postpartum haemorrhage at our center between January 1999 and may 2001. Patients were divided in two groups. In group I (208 patients) misoprostol was used in a dose of 800 ugr and in group II (192 patients) in whom misoprostol was not used. Both groups were treated initially with our conventional oxytocin protocol. We evaluated the use of additional oxytocin or ergotamine, haemoglobin levels pre and post-partum, the amount of blood loss, and the need for blood transfusion or hysterectomy. RESULTS: The need for additional oxytocin or ergotamine was reduced to less than 10% in group I when compared to group II; the drop in haemoglobin levels and the amount of blood loss were also less in group I (p: 0.03). In this group only one patient needed for blood transfusion and no patient needed hysterectomy. In group II six patients need a blood transfusion and there was the need for two hysterectomies. CONCLUSION: The use of vaginal misoprostol is effective to control the postpartum bleeding, reducing the blood loss after birth in women with high risk of post-partum haemorrhage as well as the need for blood transfusion. It's use has mild side effects and is of low cost.

Employment status and indirect costs in patients with renal failure: differences between different modalities of renal replacement therapy.

BACKGROUND: There are evidences of a different employment status between patients undergoing different modalities of renal replacement therapy (RRT). OBJECTIVES: The present study aims to compare the indirect costs associated to morbidity in the following RRT alternatives: hemodialysis in a specialized center (HD), automated peritoneal dialysis (APD), continuous ambulatory dialysis (CAPD), and renal transplant (TX). METHODS: An analysis on indirect costs was implemented following the Human Capital Theory. In total, 243 patients in working age were included (32 CAPD, 46 APD, 83 HD and 82 TX) from 8 hospitals. The potentially productive years of life lost (PPYL), the costs of lost labor productivity (LLPc) for the year 2009 and the total cost of PPYL (PPYLtc) until age of retirement were estimated. All the estimations were adjusted by age, sex rates. Non-parametric analysis (a bootstrap confidence intervals of differences in costs calculated following the simple bias-corrected percentile method -1,000 estimates-) was computed to highlight differences in costs. RESULTS: No significant differences were found in age or sex between groups. LLPc-2009- in HD (6,547€-95% CI: 5,727€-7,366€) was significantly higher (p<.001) than TX (5,079€-95% CI: 4,127€-6,030€) or APD (4,359€-95% CI: 3,064€-5,655€) but not CAPD (5,785€-95% CI: 4,302€-7,269€). PPYLs were: HD 12.58 years-95% CI: 10.42-14.73; TX 10.05-95% CI: 7.45-12.65; APD 6.09-95% CI: 3.43-8.74; CAPD 10.69-95% CI: 6.14-15.23. PPYLtc was higher in HD than in TX, APD or CAPD in all the provided scenarios. CONCLUSIONS: TX and, specially, APD are the modalities of RRT with the lowest impact on indirect costs due to morbidity showing higher rates of employment than HD and requiring less disability benefits.