Patient Preferences in Pulmonary Arterial Hypertension, a Latent Class Analysis to Identify Preference Heterogeneity.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a chronic, progressive disease of the pulmonary circulation characterized by vascular remodeling that, if untreated, can lead to right heart dysfunction and death. This analysis measured heterogeneity in patient preferences for PAH-specific treatment regimens. METHOD: Adult patients with PAH with slight to marked limitations during physical activity were recruited through a patient organization in Germany. Participants completed an online best-worst scaling case 3 survey. Patients chose among 3 hypothetical treatment profiles defined by 6 benefits and risks at varying levels. Participants completed 12 choice tasks. Preference heterogeneity was assessed using latent class analysis. RESULTS: A total of 83 participants (76% female) completed the survey. Best-fit model revealed 4 classes. Class 1 (19% of participants) assigned importance to multiple attributes particularly side effects, class 2 (34%) to physical activity limitations, class 3 (30%) to survival and physical activity limitations, and class 4 (17%) to survival. No differences in sociodemographic characteristics were observed across classes. Compared with other classes, class 4 was most likely to report having marked physical activity limitations (79%) and needing daily help (100%), while considering higher daily activity levels to be ordinary (walking >1 km [71%] or climbing several flights of stairs [50%]). CONCLUSION: This first patient preference study in a PAH population suggests that physical activity limitations in addition to survival matter most to patients; however, preference heterogeneity between groups of patients was observed. Patient preferences should be considered in treatment decision making to better balance patient's expectations regarding the known risk-benefit ratio of treatment.

Preferences for preventive treatments for rheumatoid arthritis: discrete choice survey in the UK, Germany and Romania.

OBJECTIVE: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. METHODS: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit-risk trade-offs and predicted treatment uptake was subsequently calculated. RESULTS: Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. CONCLUSION: Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

Suitability of Preference Methods Across the Medical Product Lifecycle: A Multicriteria Decision Analysis.

OBJECTIVES: This study aimed to understand the importance of criteria describing methods (eg, duration, costs, validity, and outcomes) according to decision makers for each decision point in the medical product lifecycle (MPLC) and to determine the suitability of a discrete choice experiment, swing weighting, probabilistic threshold technique, and best-worst scale cases 1 and 2 at each decision point in the MPLC. METHODS: Applying multicriteria decision analysis, an online survey was sent to MPLC decision makers (ie, industry, regulatory, and health technology assessment representatives). They ranked and weighted 19 methods criteria from an existing performance matrix about their respective decisions across the MPLC. All criteria were given a relative weight based on the ranking and rating in the survey after which an overall suitability score was calculated for each preference elicitation method per decision point. Sensitivity analyses were conducted to reflect uncertainty in the performance matrix. RESULTS: Fifty-nine industry, 29 regulatory, and 5 health technology assessment representatives completed the surveys. Overall, "estimating trade-offs between treatment characteristics" and "estimating weights for treatment characteristics" were highly important criteria throughout all MPLC decision points, whereas other criteria were most important only for specific MPLC stages. Swing weighting and probabilistic threshold technique received significantly higher suitability scores across decision points than other methods. Sensitivity analyses showed substantial impact of uncertainty in the performance matrix. CONCLUSION: Although discrete choice experiment is the most applied preference elicitation method, other methods should also be considered to address the needs of decision makers. Development of evidence-based guidance documents for designing, conducting, and analyzing such methods could enhance their use.

Social determinants of health associated with COVID-19 severity during pregnancy: a multinational cohort study (in the International Registry of Coronavirus Exposure in Pregnancy).

BACKGROUND: The COVID-19 pandemic has caused morbidity and mortality, particularly among vulnerable populations. We aimed to assess social and demographic characteristics associated with COVID-19 severity among symptomatic participants during pregnancy. METHODS: The International Registry of Coronavirus Exposure in Pregnancy is a multinational, longitudinal observational cohort study of adult participants tested for SARS-CoV-2 or who received clinical diagnosis of COVID-19 during pregnancy (NCT04366986). Disease severity status of mild, moderate, or severe was determined based on symptoms and healthcare utilization. Stratified by current versus recent pregnancy at enrollment, univariate mixed-effects logistic regression modeling was used to characterize association between social and demographic characteristics with COVID-19 severity, using a cumulative mixed effect model with country as a random effect. RESULTS: The odds of developing more severe COVID-19 (odds ratio [95% confidence interval]) were higher among participants with lower socioeconomic status (poor: 2.72 [2.01,3.69]; lower-middle class: 2.07 [1.62,2.65] vs wealthy), among participants with lower educational attainment (high school: 1.68 [1.39,2.03]; < high school (1.77 [1.25,2.51] vs graduate education). Participants over 25 years of age had lower odds of severe COVID-19 versus participants < 25 years (25-34: 0.69 [0.56,0.85]; 35-50: 0.62 [0.48,0.80]). Employment in food services was also associated with increased odds of more severe COVID-19, whereas employment in healthcare and within home, and primiparity were associated with lower severity. CONCLUSIONS: Findings suggest that employment setting and economic status have strong associations with COVID-19 severity, which warrants considering social determinants of health in the context of assessing risk factors of more severe COVID-19 during pregnancy. TRIAL REGISTRATION: IRCEP was registered with the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) [EUPAS37360] and clinicaltrials.gov [NCT04366986].

Something Is Better Than Nothing: The Value of Active Intervention in Stated Preferences for Treatments to Delay Onset of Alzheimer's Disease Symptoms.

BACKGROUND: The objective of the study was to understand respondents' willingness to accept hypothetical treatment-related risks in return for the benefit of additional time with normal memory from potential Alzheimer's disease interception therapies. METHODS: A US web-based discrete-choice survey was administered to respondents ages 60 to 85 years with no Alzheimer's disease diagnosis and no cognitive symptoms. Choice questions required respondents to indicate whether they preferred a constant, no-treatment condition described as 4 years of normal memory followed by 3 years of cognitive impairment and 5 years of dementia or an interception treatment with chosen risks of disabling stroke and death, but with increased duration of normal memory. The study design included internal validity tests to verify data quality. RESULTS: On average, respondents were willing to accept a 5% to 13% risk of stroke or death in the first year for treatments that could provide 1 or more additional years with normal memory. Nevertheless, 30% of respondents failed a simple internal-validity test question where the treatment alternative offered no improvement in disease progression but had significant side effects. These respondents also were more likely to choose active treatment in the subsequent series of choice questions. This unexpected finding is consistent with hopeful attitudes of patients with debilitating and potentially fatal conditions. CONCLUSION: Pro-treatment attitudes are clinically relevant and can affect the analysis and interpretation of stated-preference data. Internal-validity tests generally are underutilized in preference research. This study demonstrated how analysis of apparent validity failures can yield important insights about patient preferences.

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.

PURPOSE: Long-acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma-related deaths, but the effect on asthma-related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources. METHODS: Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.4 for the asthma mortality rate ratio and ≤0.40 per 10 000 person-years for the mortality rate difference, assuming no effect of new use of combined LABA + ICS (versus non-LABA maintenance therapy) on asthma mortality. Ten research institutions executed centrally distributed analytic code based on a standard protocol using an extracted (2000-2010) persistent asthma cohort (asthma diagnosis and ≥4 asthma medications in 12 months). Pooled results were analyzed by the coordinating center. Asthma deaths were ascertained by linkage with the National Death Index. RESULTS: In a cohort of 994 627 persistent asthma patients (2.4 million person-years; 278 asthma deaths), probabilities of the upper 95% confidence limit for effect estimates being less than targeted values, assuming a null relation, were about 0.05. Modifications in cohort and exposure definitions increased exposed person-time and outcome events, but study size remained insufficient to attain study goals. CONCLUSIONS: Even with 10 data sources and a 10-year study period, the rarity of asthma deaths among patients using certain medications made it infeasible to study the association between combined LABA + ICS and asthma mortality with our targeted level of study precision. Copyright © 2016 John Wiley & Sons, Ltd.

Correction to: Effect of inhaled corticosteroid particle size on asthma efficacy and safety outcomes: a systematic literature review and meta-analysis.

CORRECTION: After publication of this work [1] it was noticed that the author name Rachael L. DiSantostefano was not spelt correctly as there was a space in her surname between 'Di' and 'Santostefano'. The publisher apologises for this error.

Research Priorities to Increase Confidence in and Acceptance of Health Preference Research: What Questions Should be Prioritized Now?

BACKGROUND AND OBJECTIVE: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community. METHODS: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers. The online survey consisted of an initial importance prioritization task, a best-worst scaling case 1 instrument, and open-ended questions. Rating counts were used for analysis. The best-worst scaling used a balanced incomplete block design. RESULTS: One hundred and one participants responded to the survey invitation with 66 completing the best-worst scaling. The most important research topics related to the synthesis of preferences across studies, transferability across populations or related diseases, and method topics including comparison of methods and non-discrete choice experiment methods. Prioritization differences were found between respondents whose primary affiliation was academia versus other stakeholders. Academic researchers prioritized methodological/less studied topics; other stakeholders prioritized applied research topics relating to consistency of practice. CONCLUSIONS: As the field of health preference research grows, there is a need to revisit and communicate previous work on preference selection and study design to ensure that new stakeholders are aware of this work and to update these works where necessary. These findings might encourage discussion and alignment among different stakeholders who might hold different research priorities. Research on the application of previous preference research to new contexts will also help increase the acceptance of health preference information by decision makers.

An evaluation of asthma medication utilization for risk evaluation and mitigation strategies (REMS) in the United States: 2005-2011.

PURPOSE: The purpose of this study was to assess drug utilization patterns of fluticasone propionate (FP)/salmeterol (SAL) combination (FSC) and SAL over the 7-year period of 2005-2011 in patients with asthma as part of the Risk Evaluation and Mitigation Strategies (REMS). METHODS: A descriptive, retrospective observational study utilizing national pharmacy data and employer-based claims data to characterize drug utilization patterns. RESULTS: For patients with asthma, the total number of FSC and SAL dispensings and users of FSC and SAL has declined between 2005 and 2011. During this period, FSC and SAL dispensing for asthma decreased 24% and 76%, respectively, with a more pronounced decline between 2010 and 2011 relative to other years. The total number of patients with asthma who were dispensed FSC has decreased by 10% among adults and by 40% in children and adolescents. While SAL-containing medications decreased, dispensing of FP monotherapy increased 39% during the same 7-year period. The number of patients dispensed FP for asthma has increased 47% in children 4-11 years of age, 72% in adolescents 12-17 years of age, and 6% in adults. SAL use without a controller was infrequent and decreasing, reported by 1.7% and 0.5% of patients with asthma in 2005 and 2011, respectively. CONCLUSIONS: In patients with asthma, use of FSC and SAL decreased between 2005 and 2011, while the use of FP increased. Use of SAL monotherapy was infrequent and declined during the study period. The data suggest that the substantial communication activities have encouraged appropriate prescribing of long-acting ß2-adrenergic agonist (LABA).

Chronic respiratory disease, comorbid cardiovascular disease and mortality in a representative adult US cohort.

BACKGROUND AND OBJECTIVE: We sought to determine the relationship between chronic respiratory disease, cardiovascular disease (CVD) and mortality in a nationally representative cohort of the US population aged 40 years and older. METHODS: We analysed data from the baseline (1988-1994) and follow-up of the Third National Health and Nutrition Examination Survey (NHANES III). Subjects were classified in to one of four categories: obstructed (forced expiratory volume in 1 s/forced vital capacity <70% and forced expiratory volume in 1 s <80% predicted), restricted (forced expiratory volume in 1 s/forced vital capacity ≥70% and forced vital capacity <80% predicted), symptomatic (neither obstructed nor restricted but reporting respiratory symptoms) and normal (none of the above). Subjects were classified as having overt CVD, CVD risk factors only or neither at the baseline examination. RESULTS: The analysis data set included 9054 subjects, of whom 1132 (12.0%, weighted percentage (WP)) were obstructed, 1319 (10.3%, WP) were restricted and 2457 were symptomatic (27.6%, WP). Overt CVD was present at baseline in 1284 subjects (10.4 %, WP), and CVD risk factors alone were present in 4900 (53.3%, WP). Three thousand five hundred seventy-one (28.4%, WP) subjects died during the up to 18-year follow-up period. When compared with 'normal' subjects, those in the obstructed group were more likely to have overt CVD (odds ratio 1.87, 95% confidence interval: 1.15-3.04, P < 0.001), with a similar risk seen in the restricted and symptomatic group. CONCLUSIONS: In this large US population-based cohort, the presence of obstruction, restriction or respiratory symptoms alone was associated with higher adjusted risk of overt CVD.

Systematic review of quantitative preference studies of treatments for rheumatoid arthritis among patients and at-risk populations.

Treatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed.

Acceptable risks of treatments to prevent rheumatoid arthritis among first-degree relatives: demographic and psychological predictors of risk tolerance.

OBJECTIVES: To quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA). METHODS: Preventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks. Using a probabilistic threshold technique, each risk was increased or decreased until participants switched their choice. Perceived risk of RA, health literacy, numeracy, Brief Illness Perception Questionnaire and Beliefs about Medicines Questionnaire-General were also assessed. Maximum acceptable risk (MAR) was summarised using descriptive statistics. Associations between MARs and participants' characteristics were assessed using interval regression with effects coding. RESULTS: 289 FDRs (80 male) responded. The mean MAR for a 40% reduction in chance of developing RA was 29.08% risk of mild side effects, 9.09% risk of serious infection and 0.85% risk of a serious side effect. Participants aged over 60 years were less tolerant of serious infection risk (mean MAR ±2.06%) than younger participants. Risk of mild side effects was less acceptable to participants who perceived higher likelihood of developing RA (mean MAR ±3.34%) and more acceptable to those believing that if they developed RA it would last for a long time (mean MAR ±4.44%). CONCLUSIONS: Age, perceived chance of developing RA and perceived duration of RA were associated with tolerance to some risks of preventive RA therapy.

Exploring Decisional Conflict With Measures of Numeracy and Optimism in a Stated Preference Survey.

OBJECTIVES: Low optimism and low numeracy are associated with difficulty or lack of participation in making treatment-related health care decisions. We investigated whether low optimism and low self-reported numeracy scores could help uncover evidence of decisional conflict in a discrete-choice experiment (DCE). METHODS: Preferences for a treatment to delay type 1 diabetes were elicited using a DCE among 1501 parents in the United States. Respondents chose between two hypothetical treatments or they could choose no treatment (opt out) in a series of choice questions. The survey included a measure of optimism and a measure of subjective numeracy. We used latent class analyses where membership probability was predicted by optimism and numeracy scores. RESULTS: Respondents with lower optimism scores had a higher probability of membership in a class with disordered preferences (P value for optimism coefficient = 0.032). Those with lower self-reported numeracy scores were more likely to be in a class with a strong preference for opting out and disordered preferences (P = 0.000) or a class with a preference for opting out and avoiding serious treatment-related risks (P = 0.015). CONCLUSIONS: If respondents with lower optimism and numeracy scores are more likely to choose to opt out or have disordered preferences in a DCE, it may indicate that they have difficulty completing choice tasks.

Quantitative Benefit-Risk Assessment: State of the Practice Within Industry.

BACKGROUND: Benefit-risk assessments for medicinal products and devices have advanced significantly over the past decade. The purpose of this study was to characterize the extent to which the life sciences industry is utilizing quantitative benefit-risk assessment (qBRA) methods. METHODS: Semi-structured interviews were conducted with a sample of industry professionals working in drug and/or medical device benefit-risk assessments (n = 20). Questions focused on the use, timing, and impact of qBRA; implementation challenges; and future plans. Interviews were recorded, transcribed, and coded for thematic analysis. RESULTS: While most surveyed companies had applied qBRA, application was limited to a small number of assets-primarily to support internal decision-making and regulatory submissions. Positive impacts associated with use included improved team decision-making and communication. Multi-criteria decision analysis and discrete choice experiment were the most frequently utilized qBRA methods. A key challenge of qBRA use was the lack of clarity regarding its value proposition. Championing by senior company leadership and receptivity of regulators to such analyses were cited as important catalysts for successful adoption of qBRA. Investment in qBRA methods, via capability building and pilot studies, was also under way in some instances. CONCLUSION: qBRA application within this sample of life sciences companies was widespread, but concentrated in a small fraction of assets. Its use was primarily for internal decision-making or regulatory submissions. While some companies had plans to build further capacity in this area, others were waiting for further regulatory guidance before doing so.

Treatment preferences for preventive interventions for rheumatoid arthritis: protocol of a mixed methods case study for the Innovative Medicines Initiative PREFER project.

INTRODUCTION: Amidst growing consensus that stakeholder decision-making during drug development should be informed by an understanding of patient preferences, the Innovative Medicines Initiative project 'Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle' (PREFER) is developing evidence-based recommendations about how and when patient preferences should be integrated into the drug life cycle. This protocol describes a PREFER clinical case study which compares two preference elicitation methodologies across several populations and provides information about benefit-risk trade-offs by those at risk of rheumatoid arthritis (RA) for preventive interventions. METHODS AND ANALYSIS: This mixed methods study will be conducted in three countries (UK, Germany, Romania) to assess preferences of (1) first-degree relatives (FDRs) of patients with RA and (2) members of the public. Focus groups using nominal group techniques (UK) and ranking surveys (Germany and Romania) will identify and rank key treatment attributes. Focus group transcripts will be analysed thematically using the framework method and average rank orders calculated. These results will inform the treatment attributes to be assessed in a survey including a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT). The survey will also include measures of sociodemographic variables, health literacy, numeracy, illness perceptions and beliefs about medicines. The survey will be administered to (1) 400 FDRs of patients with RA (UK); (2) 100 FDRs of patients with RA (Germany); and (3) 1000 members of the public in each of UK, Germany and Romania. Logit-based approaches will be used to analyse the DCE and imputation and interval regression for the PTT. ETHICS AND DISSEMINATION: This study has been approved by the London-Hampstead Research Ethics Committee (19/LO/0407) and the Ethics Committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg (92_17 B). The protocol has been approved by the PREFER expert review board. The results will be disseminated widely and will inform the PREFER recommendations.

Parent Preferences for Delaying Insulin Dependence in Children at Risk of Stage III Type 1 Diabetes.

Background: Autoantibody screening in type 1 diabetes (T1D) may reduce the chances of potentially life-threatening diabetic ketoacidosis (DKA) at diagnosis by allowing individuals at risk of progression to more actively monitor for and/or manage progression to insulin dependence. We investigated parents' preferences for treatments to delay the onset of insulin dependence in children who are at high risk of developing Stage III T1D. Methods: A web-based survey (n = 1501) was administered to a stratified sample of parents (children <18 years) in the United States from an online panel. Parents were told to hypothetically assume that their youngest child would become insulin dependent within 6 months or 2 years and were offered a series of choices between no treatment and two hypothetical treatments that would delay insulin dependence. Random-parameters logit analysis and maximum acceptable risks were used to evaluate the relative importance of treatment benefits and risks. Results: Most parents chose at least one active treatment (2% always chose monitoring only). For parents of children without T1D (n = 901), delaying insulin dependence and reducing the risk of long-term health complications and serious infection were the most important treatment attributes. In addition, parents of children with T1D (n = 600) also valued reducing the risk of hospitalizations due to DKA. Conclusions: When told to assume their child would develop Stage III T1D, most parents considered active treatments to delay progression. For medicines under development to delay insulin dependence in T1D, the preferences expressed in this survey provide guidance on acceptable benefit-risk trade-offs.

[Changes in asthma insights and reality in Japan (AIRJ) in 2005 since 2000].

BACKGROUND: A cross-sectional survey, Asthma Insights and Reality in Japan (AIRJ) conducted in 2000 demonstrated that the level of asthma control and inhaled corticosteroid (ICS) use in Japanese asthmatics were low compared to the average in European countries. The purpose of the AIRJ survey in 2005 was to assess changes in the burden of asthma and asthma management in Japan since 2000 AIRJ survey. METHODS: We used identical methods to AIRJ 2000, including random-digit dialing to identify current asthmatics throughout Japan in 2005. A detailed telephone survey which included items on the burden of asthma and clinical management was conducted in 800 households (400 adults, 400 children) from the identified asthmatics. We compared AIRJ 2005 results with those of AIRJ 2000 separately for adults and children with statistical adjustment for differences in population characteristics between AIRJ 2000 and AIRJ 2005. RESULTS: Participants in 2005 reported significantly lower prevalence of symptoms, including a decrease in daytime symptoms in adults (52% to 46%, p=0.046) and a decrease in night-time awaking in children (40% to 33%, p=0.039). The number of patients who experienced one or more asthma episodes in the past year (ER visits, hospitalization, or unscheduled doctor visits) decreased significantly from 2000 in adults (41% to 31%, p<0.01) and children (62% to 49%, p<0.001). ICS use rate increased significantly in adults (12% to 18%, p=0.019) and had a tendency to increase in children (5% to 8%, p=0.059). CONCLUSIONS: There have been improvements in the burden of asthma patients and clinical disease management as well as more use of ICS in Japan since 2000. Nevertheless, in most patients, ICS use still remained low, and asthma management fell short of the goals of treatment outlined in the Japanese guidelines. There is a need to increase awareness of and compliance with the asthma guidelines and to popularize standardized therapy in Japan.

The long-term cost effectiveness of treatments for benign prostatic hyperplasia.

INTRODUCTION: Excellent treatment outcomes with long-term durability and few adverse effects are expectations of treatments for chronic conditions. The long-term cost effectiveness of newer treatments for benign prostatic hyperplasia (BPH), including high-energy transurethral microwave thermotherapy (TUMT) and combination pharmaceutical therapy, has not been sufficiently studied against existing alternatives. The objective of this study was to estimate the incremental cost effectiveness of BPH treatment alternatives. METHODS: We employed a Markov model over a 20-year time horizon and the payer's perspective to evaluate the cost effectiveness of watchful waiting (WW), pharmaceuticals (alpha-adrenoceptor antagonists [alpha-blockers], 5-alpha-reductase inhibitors [5-ARIs], combination therapy), TUMT and transurethral resection of the prostate (TURP) in treating BPH. Markov states included improvement in symptoms, no improvement in symptoms, adverse effects and death. We used data from the published literature for outcomes, including systematic reviews whenever possible. Costs were estimated using a managed-care claims database and Medicare fee schedules, and were reported in Dollars US, 2004 values. Costs and effectiveness outcomes were discounted at a rate of 3% per year. Men (aged > or =45 years) with moderate to severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age and BPH symptom levels. Outcomes included costs, QALYs, incremental cost-utility ratios and cost-effectiveness acceptability curves. Sensitivity analysis was performed on important parameters, with an emphasis on probabilistic sensitivity analysis. RESULTS: alpha-Blockers and TUMT were cost effective for treating moderate symptoms using the threshold of Dollars US 50,000 per QALY. For example, at 65 years of age, the cost per QALY was Dollars US 16,018 for alpha-blockers compared with WW and Dollars US 30,204 for TUMT versus alpha-blockers. TURP was the most cost-effective treatment for severe symptoms (Dollars US 5824 per QALY ) versus WW. Model results were robust to changes in costs and sensitive to the assumed probabilities, utility weights, extent of improvement and life expectancy. Nevertheless, acceptability curves consistently demonstrated the same alternatives as most likely to be cost effective. CONCLUSIONS: Our model suggests that alpha-blockers and TURP appear to be the most cost-effective alternatives, from a US payer perspective, for BPH patients with moderate and severe symptoms, respectively. TUMT was promising for patients with moderate symptoms and the oldest patients with severe symptoms, but otherwise was dominated. Value of information analysis could be used to determine the net benefit of additional research.

Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis.

OBJECTIVES: To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility). DESIGN: Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations. SETTING: Global. PARTICIPANTS: 3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year. INTERVENTIONS: FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day. OUTCOME MEASURES: Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy. RESULTS: Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58). Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility. CONCLUSIONS: In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations. In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation. TRIAL REGISTRATION NUMBERS: NCT01009463; NCT01017952; Post-results.