A Proposal of a Cost-Effectiveness Modeling Approach for Heart Failure Treatment Assessment: Considering the Short- and Long-Term Impact of Hospitalization on Event Rates.

BACKGROUND: The rate of events such as recurrent heart failure (HF) hospitalization and death are known to dramatically increase directly after HF hospitalization. Furthermore, the number of HF hospitalizations is associated with irreversible long-term disease progression, which is in turn associated with increased event rates. However, cost-effectiveness models of HF treatments commonly fail to capture both the short- and long-term association between HF hospitalization and events. OBJECTIVE: The aim of this study was to provide a decision-analytic model that reflects the short- and long-term association between HF hospitalization and event rates. Furthermore, we assess the impact of omitting these associations. METHODS: We developed a life-time Markov cohort model to evaluate HF treatments, and modeled the short-term impact of HF hospitalization on event rates via a sequence of tunnel states, with transition probabilities following a parametric survival curve. The corresponding long-term impact was modeled via hazard ratios per HF hospitalization. We obtained baseline event rates and utilities from published literature. Subsequently, we assessed, for a hypothetical HF treatment, how omitting the modeled associations (through a simple two-state model) affects incremental quality-adjusted life-years (QALYs). RESULTS: We developed a model that incorporates both short- and long-term impacts of HF hospitalizations. Based on an assumed treatment effect of a 20% risk reduction for HF hospitalization (and associated reductions in all-cause mortality of 15%), omitting the short-term, the long-term, or both associations resulted in a 5%, 1%, and 22% decrease in QALYs gained, respectively. CONCLUSION: For both modeling components, i.e., the short- and long-term implications of HF hospitalization, the impact on incremental outcomes associated with treatment was substantial. Considering these aspects as proposed within this modeling approach better reflects the natural course of this progressive condition and will enhance the evaluation of future HF treatments.

The impact of heart failure on patients and caregivers: A qualitative study.

BACKGROUND: Heart failure is rising in prevalence but relatively little is known about the experiences and journey of patients and their caregivers. The goal of this paper is to present the symptom and symptom impact experiences of patients with heart failure and their caregivers. METHODS: This was a United States-based study wherein in-person focus groups were conducted. Groups were audio recorded, transcribed and a content-analysis approach was used to analyze the data. RESULTS: Ninety participants (64 patients and 26 caregivers) were included in the study. Most patients were female (52.0%) with mean age 59.3 ± 8 years; 55.6% were New York Heart Association Class II. The most commonly reported symptoms were shortness of breath (81.3%), fatigue/tiredness (76.6%), swelling of legs and ankles (57.8%), and trouble sleeping (50.0%). Patients reported reductions in social/family interactions (67.2%), dietary changes (64.1%), and difficulty walking and climbing stairs (56.3%) as the most common adverse disease impacts. Mental-health sequelae were noted as depression and sadness (43.8%), fear of dying (32.8%), and anxiety (32.8%). Caregivers (mean age 55.5 ± 11.2 years and 52.0% female) discussed 33 daily heart failure impacts, with the top three being reductions in social/family interactions (50.0%); being stressed, worried, and fearful (46.2%); and having to monitor their "patience" level (42.3%). CONCLUSIONS: There are serious unmet needs in HF for both patients and caregivers. More research is needed to better characterize these needs and the impacts of HF along with the development and evaluation of disease management toolkits that can support patients and their caregivers.

Health State Utilities of Patients with Heart Failure: A Systematic Literature Review.

BACKGROUND AND OBJECTIVES: New treatments and interventions are in development to address clinical needs in heart failure. To support decision making on reimbursement, cost-effectiveness analyses are frequently required. A systematic literature review was conducted to identify and summarize heart failure utility values for use in economic evaluations. METHODS: Databases were searched for articles published until June 2019 that reported health utility values for patients with heart failure. Publications were reviewed with specific attention to study design; reported values were categorized according to the health states, 'chronic heart failure', 'hospitalized', and 'other acute heart failure'. Interquartile limits (25th percentile 'Q1', 75th percentile 'Q3') were calculated for health states and heart failure subgroups where there were sufficient data. RESULTS: The systematic literature review identified 161 publications based on data from 142 studies. Utility values for chronic heart failure were reported by 128 publications; 39 publications published values for hospitalized and three for other acute heart failure. There was substantial heterogeneity in the specifics of the study populations, methods of elicitation, and summary statistics, which is reflected in the wide range of utility values reported. EQ-5D was the most used instrument; the interquartile limit for mean EQ-5D values for chronic heart failure was 0.64-0.72. CONCLUSIONS: There is a wealth of published utility values for heart failure to support economic evaluations. Data are heterogenous owing to specificities of the study population and methodology of utility value elicitation and analysis. Choice of value(s) to support economic models must be carefully justified to ensure a robust economic analysis.

Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study.

BACKGROUND: Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)-a novel activator of cardiac myosin-improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure). METHODS: Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score. RESULTS: Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8-8.1) for placebo, 6.6 (95% CI, 3.4-9.8) for OM 25 mg (P=0.32 versus placebo), and 9.9 (95% CI, 6.7-13.0) for OM-PK (P=0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, -0.3 to 6.6), 6.0 (95% CI, 3.1-8.9) for OM 25 mg (P=0.12), and 4.3 (95% CI, 0.7-7.9) for OM-PK (P=0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4-6.9) for placebo, 6.3 (95% CI, 3.6-9.0) for OM 25 mg (P=0.19), and 7.0 (95% CI, 4.1-10.0) for OM-PK (P=0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline. CONCLUSIONS: HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01786512.

Real-World Analysis of Guideline-Based Therapy After Hospitalization for Heart Failure.

Background Patients hospitalized with heart failure (HF) with reduced ejection fraction have high risk of rehospitalization or death. Despite guideline recommendations based on high-quality evidence, a substantial proportion of patients with HF with reduced ejection fraction receive suboptimal care and/or do not comply with optimal care following hospitalization. Methods and Results This retrospective observational study identified 17 106 patients with HF with reduced ejection fraction with an incident HF-related hospitalization using the Humana Medicare Advantage database (2008-2016). HF medication classes (beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, or mineralocorticoid receptor antagonists) received in the year after hospitalization were recorded, and categorized by treatment intensity (ie, number of concomitant medication classes received: none [23% of patients; n=3987], monotherapy [22%; n=3777], dual therapy [41%; n=7056], or triple therapy [13%; n=2286]). Compared with no medication, risk of primary outcome (composite of death or rehospitalization) was significantly reduced (hazard ratio [95% CI]) with monotherapy (0.68 [0.64-0.71]), dual therapy (0.56 [0.53-0.59]), and triple therapy (0.45 [0.41-0.50]). Nearly half (46%) of patients who received post-discharge medication had no dose escalation. Overall, 59% of patients had follow-up with a primary care physician within 14 days of discharge, and 23% had follow-up with a cardiologist. Conclusions In real-world clinical practice, increasing treatment intensity reduced risk of death and rehospitalization among patients hospitalized for HF, though the use of guideline-recommended dual and triple HF therapy remained low. There are opportunities to improve post-discharge medical management for patients with HF with reduced ejection fraction such as optimizing dose titration and improving post-discharge follow-up with providers.

A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020).

BACKGROUND: Heart failure presents a growing clinical and economic burden in the USA. Robust cost data on the burden of illness are critical to inform economic evaluations of new therapeutic interventions. OBJECTIVES: This systematic literature review of heart failure-related costs in the USA aimed to assess the quality of the published evidence and provide a narrative synthesis of current data. METHODS: Four electronic databases (MEDLINE, EMBASE, EconLit, and the Centre for Reviews and Dissemination York Database, including the NHS Economic Evaluation Database and Health Technology Assessment Database) were searched for journal articles published between January 2014 and March 2020. The review, registered with PROSPERO (CRD42019134201), was restricted to cost-of-illness studies in adults with heart failure events in the USA. RESULTS: Eighty-seven studies were included, 41 of which allowed a comparison of cost estimates across studies. The annual median total medical costs for heart failure care were estimated at $24,383 per patient, with heart failure-specific hospitalizations driving costs (median $15,879 per patient). Analyses of subgroups revealed that heart failure-related costs are highly sensitive to individual patient characteristics (such as the presence of comorbidities and age) with large variations even within a subgroup. Additionally, differences in study design and a lack of standardized reporting limited the ability to compare cost estimates. The finding that costs are higher for patients with heart failure with reduced ejection fraction compared with patients with preserved ejection fraction highlights the need for differentiating among different heart failure types. CONCLUSIONS: The review underpins the conclusion drawn in earlier reviews, namely that hospitalization costs are the key driver of heart failure-related costs. Analyses of subgroups provide a clearer understanding of sources of heterogeneity in cost data. While current cost estimates provide useful indications of economic burden, understanding the nuances of the data is critical to support its application.

Correction: Evaluating risk prediction models for adults with heart failure: A systematic literature review.

[This corrects the article DOI: 10.1371/journal.pone.0224135.].

Evaluating risk prediction models for adults with heart failure: A systematic literature review.

BACKGROUND: The ability to predict risk allows healthcare providers to propose which patients might benefit most from certain therapies, and is relevant to payers' demands to justify clinical and economic value. To understand the robustness of risk prediction models for heart failure (HF), we conducted a systematic literature review to (1) identify HF risk-prediction models, (2) assess statistical approach and extent of validation, (3) identify common variables, and (4) assess risk of bias (ROB). METHODS: Literature databases were searched from March 2013 to May 2018 to identify risk prediction models conducted in an out-of-hospital setting in adults with HF. Distinct risk prediction variables were ranked according to outcomes assessed and incorporation into the studies. ROB was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: Of 4720 non-duplicated citations, 40 risk-prediction publications were deemed relevant. Within the 40 publications, 58 models assessed 55 (co)primary outcomes, including all-cause mortality (n = 17), cardiovascular death (n = 9), HF hospitalizations (n = 15), and composite endpoints (n = 14). Few publications reported detail on handling missing data (n = 11; 28%). The discriminatory ability for predicting all-cause mortality, cardiovascular death, and composite endpoints was generally better than for HF hospitalization. 105 distinct predictor variables were identified. Predictors included in >5 publications were: N-terminal prohormone brain-natriuretic peptide, creatinine, blood urea nitrogen, systolic blood pressure, sodium, NYHA class, left ventricular ejection fraction, heart rate, and characteristics including male sex, diabetes, age, and BMI. Only 11/58 (19%) models had overall low ROB, based on our application of PROBAST. In total, 26/58 (45%) models discussed internal validation, and 14/58 (24%) external validation. CONCLUSIONS: The majority of the 58 identified risk-prediction models for HF present particular concerns according to ROB assessment, mainly due to lack of validation and calibration. The potential utility of novel approaches such as machine learning tools is yet to be determined. REGISTRATION NUMBER: The SLR was registered in Prospero (ID: CRD42018100709).

Economic Evaluations of Pharmacological Treatments in Heart Failure Patients: A Methodological Review with a Focus on Key Model Drivers.

Various decision analytic models exist for evaluating the cost-effectiveness of pharmacological interventions for heart failure (HF). Despite this, studies that explore drivers influencing these modeling approaches remain scarce. Through a systematic review of the literature, the present study sought to identify model drivers that emerge from economic evaluations of HF pharmacological interventions. Among the 72 cost effectiveness papers evaluating HF drug interventions, the most frequently identified, top 5 ranked model drivers impacting the incremental cost-effectiveness ratio (ICER) were cost of treatment and utility, identified in 10% of studies, respectively. Other drivers that emerged as top 5 ranked drivers in > 5% of studies included treatment effect on mortality (or cardiovascular mortality), duration of treatment, and baseline cardiovascular mortality. Model drivers reported at the top of tornado diagrams were treatment effect on mortality or on cardiovascular mortality. Collectively, these observations highlight the key importance of treatment effect in driving cost-effectiveness models for HF.

Evaluating minimal important differences and responder definitions for the asthma symptom diary in patients with moderate to severe asthma.

BACKGROUND: The Asthma Symptom Diary was developed to assess severity of symptoms in patients with moderate to severe asthma, and has evidence supporting reliability and validity. Only limited information is available on sensitivity to change and responder definitions for the Asthma Symptom Diary. OBJECTIVES: Main study objectives were to evaluate sensitivity to change and provide responder definitions for clinically meaningful effects for the Asthma Symptom Diary. METHODS: This is a secondary analysis of Phase II clinical trial data in patients with moderate to severe asthma, Asthma Symptom Diary (ASD) was collected daily during the 24-week study. The Asthma Control Questionnaire and the Patient Global Assessment were collected at baseline, and week 12 and 24. Analysis of covariance (ANCOVA) models were used to evaluate sensitivity to change in Asthma Symptom Diary scores after 12 and 24 weeks of treatment. Anchor-based methods, using Asthma Control Questionnaire and Patient Global Assessment defined anchors, were used to identify minimal important differences and various responder criteria for changes in mean 7-day ASD score, symptomatic days, and minimal symptom days. RESULTS: Sample was 59% female, 81% White, with a mean age of 47.3 (SD = 13.6) years. ANCOVAs demonstrated significant differences in baseline to week 12 and week 24 changes in mean 7-day Asthma Symptom Diary scores and symptomatic days by Asthma Control Questionnaire (all p < 0.001) and Patient Global Assessment anchors (all p < 0.001). Meaningful responders, from the patient's perspective, were defined as improvements of 0.5-0.6 points (SD = 0.6; scale range 0 to 4) in mean 7-day Asthma Symptom Diary scores, and as a reduction of 2 to 3 Asthma Symptom Diary-based symptomatic days. CONCLUSION: The Asthma Symptom Diary was responsive to changes in clinical status in patients with moderate to severe asthma. Responder definitions were identified, including symptomatic days, for evaluating individual level treatment effects in clinical trials.

Evaluating Cost-Effectiveness Models for Pharmacologic Interventions in Adults with Heart Failure: A Systematic Literature Review.

BACKGROUND: Heart failure (HF) is a well-recognized public health concern and imposes high economic and societal costs. Decision analytic models exist for evaluating the economic ramifications associated with HF. Despite this, studies that appraise these modelling approaches for augmenting best-practice decisions remain scarce. OBJECTIVE: Our objective was to conduct a systematic literature review (SLR) of published economic models for the management of HF and describe their general and methodological features. METHODS: This SLR employed a combination of relevant search terms associated with HF, which were used in a number of databases, including MEDLINE, Embase, the National Health Service Economic Evaluation Database, Cost-Effectiveness Analysis Registry, ScHARR Health Utilities Database and Cochrane Library Database. A number of model features (i.e. model structure, specification, outcomes assessed, scenario and sensitivity analysis, key model drivers) were extracted and subsequently summarized. RESULTS: Of 64 publications retained, a selection of modelling approaches were identified, including Markov (n = 28), trial-based analytic (n = 22), discrete-event simulation (n = 6), survival analytic (n = 7) and decision-tree modelling (n = 1) approaches. The bulk of publications employed either a cost-utility (n = 27) or cost-effectiveness (n = 36) analysis and evaluated more than one study outcome, which typically included overall costs (n = 59), incremental cost-effectiveness ratios (n = 55), life-years gained (n = 48) and willingness-to-pay thresholds (n = 37). Most publications focused on patients with chronic HF (n = 40) and used New York Heart Association (NYHA) disease classifications to categorize patients and determine disease severity. Few (n = 19) publications documented the use of hospitalization states for modelling patient outcomes and associated costs. A quality assessment of the included publications revealed most articles demonstrated reasonable methodological value. CONCLUSIONS: We identified numerous decision analytic modelling approaches for evaluating the cost effectiveness of pharmacologic treatments in HF. A Markov cohort model approach was most commonly used, and most models relied on NYHA classes as a proxy of HF severity, disease progression and prognosis.

Is the EQ-5D fit for purpose in asthma? Acceptability and content validity from the patient perspective.

BACKGROUND: The increasing emphasis on patient-reported outcomes in health care decision making has prompted greater rigor in the evidence to support the instruments used. Acceptability and content validity are important properties of any measure to ensure it assesses the relevant aspects of the target concept. The purpose of this study was to evaluate the acceptability and content validity of the EQ-5D 5-Level (EQ-5D-5L) to assess the impact of asthma on patients' lives. METHODS: Qualitative interviews were conducted with 40 adults with asthma in the United Kingdom. The first 25 interviews used cognitive-debriefing methods to assess the relevance and acceptability of the EQ-5D-5L and two asthma-specific measures for comparison: an asthma-specific, preference-based measure (the Asthma Quality of Life Utility Index-5 Dimensions) and an Asthma Symptom Diary. The final 15 interviews combined concept elicitation to identify patient-perceived asthma impact, and cognitive debriefing to assess relevance and acceptability of the EQ-5D-5L and the Asthma Symptom Diary. Cognitive-debriefing feedback on the content of the measures was collated and summarized descriptively. The concept-elicitation data were analyzed thematically. RESULTS: Participants were aged 20 to 57 years and 62.5% were female. Although some participants expressed positive opinions on aspects of the EQ-5D-5L, only the usual activities dimension was consistently considered relevant to participants' asthma experiences. The mobility and self-care dimensions prompted strong negative reactions from some participants. Variations in interpretation of the mobility dimension and difficulties with multiple concepts in the pain/discomfort and anxiety/depression dimensions also were noted. Concepts reported by participants as missing included environmental triggers, asthma symptoms, emotions, and sleep. The EQ-5D-5L was the least preferred measure to describe the impact of asthma on participants' lives. Participants reported shortness of breath and impact on activities as especially salient issues. CONCLUSIONS: The content of the EQ-5D-5L was poorly aligned with the patient-perceived impact of asthma, and the measure failed to meet basic standards for acceptability and content validity as a measure to assess the impact of asthma from the patient perspective. The shortcomings identified raise concerns regarding the appropriateness of the EQ-5D in asthma and further evaluation is warranted.

Estimating asthma control questionnaire (ACQ) scores from claims data.

BACKGROUND: Asthma control is the main focus of treatment guidelines. Valid instruments such as the Asthma Control Questionnaire (ACQ) require prospective survey. These surveys may be challenging for large population health applications. OBJECTIVE: To develop an algorithm for estimating ACQ-5 scores from commonly available claims data. METHODS: Data was derived from four prospective surveys including the ACQ-5 combined with retrospective claims of Kaiser Permanente of Colorado (KPCO) patients. The statistical approach consisted of derivation and validation of a prediction algorithm including medical and pharmacy claims data using stepwise regression elimination. Validation was conducted by estimating mean squared error (MSE) and mean absolute error (MAE) in one hundred split-sample iterations. Ordinary least squares (OLS), Tobit and Median regression were used. RESULTS: There were 2,657 individuals with valid ACQ-5 scores, claims and eligibility at baseline. The following had statistically significant associations with ACQ-5 scores: gender, use of oral corticosteroids and short-acting beta agonists, the number of asthma drug classes, and emergency and outpatient visits. Average MSE and MAE were similar for the estimation and validation samples. CONCLUSION: This research provides preliminary results of the feasibility of predicting ACQ-5 scores using commonly available medical and pharmacy claims data. The resulting algorithm may facilitate public health and population level analyses of asthma control. Future studies in different populations will be important to validate the algorithm.

Oral corticosteroid exposure and adverse effects in asthmatic patients.

BACKGROUND: Significant adverse effects (AEs) have been associated with continuous exposure to oral corticosteroids (OCSs). The potential association with intermittent exposure is unknown. OBJECTIVE: We sought to assess the association between OCSs and AEs based on the number of OCS prescriptions. METHODS: This was a retrospective cohort study of asthmatic patients 18 years and older in the 2000-2014 MarketScan data set. Propensity score matching was used at baseline (12 months before the index date: first OCS use). Logistic regression was used to examine the association between OCSs and new incident AEs (either combined or individual) controlling for covariates. Follow-up continued for 24 months minimum and 10 years maximum after the index date. RESULTS: There were 72,063 and 156,373 subjects in the OCS and no OCS cohorts, respectively. Subjects taking 4 or more OCS (1-3) prescriptions within the year had 1.29 (1.04) times the odds of experiencing a new AE within the year. Each year of exposure to 4 or more OCS prescriptions (current and past) resulted in 1.20 times the odds of having an AE in the current year. Exposure to 4 or more prescriptions was associated with significantly greater odds of AEs for osteoporosis, hypertension, obesity, type 2 diabetes, gastrointestinal ulcers/bleeds, fractures, and cataracts (odds, 1.21-1.44 depending on the AE). CONCLUSION: Although previous research has documented the deleterious effect of continuous OCS exposure in patients with severe asthma, our results suggest that each OCS prescription might result in a cumulative burden on current and future health regardless of dose and duration. OCS-sparing strategies are extremely important to improve patient outcomes.

Development and validation of the Ulcerative Colitis patient-reported outcomes signs and symptoms (UC-pro/SS) diary.

BACKGROUND: The clinical course of ulcerative colitis (UC) and the effects of treatment are assessed through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of UC in clinical trials through direct report from patient ratings. DESIGN: The UC-PRO/SS was developed by collecting data from concept elicitation (focus groups, and individual interviews), then refined through a process of cognitive interviews of 57 UC patients. Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were evaluated in an observational, four-week study of adults with mild to severe UC (N = 200). RESULTS: Findings from qualitative focus groups and interviews identified nine symptom items covering bowel and abdominal symptoms. The final UC-PRO/SS daily diary includes two scales: Bowel S&S (six items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 80 and 0.66, respectively); reproducibility (intraclass correlation coefficient = 0.81, 0.71) and validity, including moderate-to-high correlations with the Partial Mayo Score (0.79; 0.45) and Inflammatory Bowel Disease Questionnaire (IBDQ) total score (- 0.70; - 0.61). Scores discriminated by level of disease severity, as defined by the Partial Mayo Score, Patient Global Rating, and Clinician Global Rating (p < 0.0001). CONCLUSIONS: Results suggest that the UC-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in UC patients. Additional longitudinal data are needed to evaluate the ability of the UC-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.

Development and validation of the Crohn's disease patient-reported outcomes signs and symptoms (CD-PRO/SS) diary.

BACKGROUND: The clinical course of Crohn's disease (CD) and the effect of its treatment are monitored through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Crohn's Disease Patient-reported Outcomes Signs and Symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of CD through direct report from patient ratings. METHODS: The CD-PRO/SS was developed based on data from concept elicitation (focus groups, interviews; n = 29), then refined through cognitive interviews of CD patients (n = 20). Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were examined using secondary analyses of baseline and two-week clinical trial data of adults with moderate-to-severe CD (n = 238). RESULTS: Findings from qualitative interviews identified nine S&S items covering bowel and abdominal symptoms. The final CD-PRO/SS daily diary includes two scales: Bowel S&S (three items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 0.74 and 0.67, respectively); reproducibility (intraclass correlation coefficient > 0.80), and validity, with the last including moderate correlations with the Inflammatory Bowel Disease Questionnaire bowel symptom score and select items (ranging from r = 0.43-0.54). Scores distinguished patients categorized by patient global ratings of disease severity (p < 0.0001). CONCLUSIONS: Results suggest the CD-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in CD patients. Additional longitudinal data are needed to evaluate the ability of the CD-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.

Measuring the cost of poor asthma control and exacerbations.

BACKGROUND: Previous studies have shown an association between cost and poor asthma control. However, longitudinal studies of general populations are lacking. OBJECTIVE: To examine the cost of poor asthma control and exacerbations across a broad spectrum of asthma patients. METHODS: The Observational Study of Asthma Control and Outcomes (OSACO) was a prospective survey of persistent asthma patients in Kaiser Colorado in 2011-2012. Patients received a survey 3 times in one year, which included the Asthma Control Questionnaire (ACQ) and questions on exacerbations. Self-reported exacerbations were compared to actual oral corticosteroid (OCS) use. Regression analyses examined the association of control (ACQ-5 scores) and exacerbations with healthcare expenditures, controlling for sociodemographics and smoking. Analyses of expenditures used Generalized Linear Models (GLM) with log-link. RESULTS: 2681 individuals completed at least one survey; 1799 completed all three. ACQ-5 scores were associated with higher all-cause and asthma-specific expenditures across all categories of costs (medical, outpatient, ER, pharmacy) except for inpatient expenditures. Each 1-point increase in the ACQ-5 score (i.e., worse control) was associated with a corresponding increase in all-cause annual healthcare and asthma-specific expenditures of $1443 and $927 ($US 2013). Asthma exacerbations with documented OCS use were associated with an increase of $3014 and $1626 over 4 months, while self-reported exacerbations were $713 and $506. CONCLUSION: Results demonstrate that poor asthma control and exacerbations are strongly associated with higher healthcare expenditures. Results also confirm that collection of validated measures of control such as the ACQ-5 may provide valuable information toward improving clinical and economic outcomes.

Health-related quality of life associated with systemic corticosteroids.

BACKGROUND: Systemic corticosteroids (SCS) are commonly used but are associated with adverse effects. Given their prevalent use, the potential impact of SCS use on health-related quality of life (HRQoL) is important to characterize. OBJECTIVE: To assess the HRQoL of patients taking SCS. METHODS: The 2000-2003 Medical Expenditure Panel Survey was used to examine EQ-5D and SF-6D scores associated with SCS use in adults. The study sample was restricted to those with a condition for which SCS are prescribed. SCS use was categorized into three levels: none; 1-3; and ≥4 prescriptions per year. HRQoL scores were regressed on SCS use (1-3 or ≥4 annual prescriptions) controlling for age, gender, race, ethnicity, education, income category, geographic region, number of ER visits, number of outpatient visits, total number of chronic conditions (for which SCS are not used) and conditions for which SCS are clinically indicated. RESULTS: There were 54,856 individuals with no SCS exposure, 2245 with 1-3 and 624 with ≥4 annual SCS prescriptions. In adjusted analyses, use of ≥4 annual SCS prescriptions appeared to be associated with significantly lower EQ-5D (US), EQ-5D (UK), SF-6D and EQ-5D VAS scores compared to no exposure: -0.032, -0.047, -0.036, and -7.58. CONCLUSION: While SCS are efficacious and widely used for numerous conditions, results suggest that their use may be associated with a substantial deleterious impact on HRQoL. This potential negative effect should be considered in balance with the cost and efficacy of comparable treatments.

Exploring asthma control cutoffs and economic outcomes using the Asthma Control Questionnaire.

BACKGROUND: Understanding the effect of worsening asthma control on expenditures and health resource utilization (HRU) is important. OBJECTIVE: To explore the association of economic outcomes with asthma control cutoffs and longitudinal changes on the Asthma Control Questionnaire 5 (ACQ-5). METHODS: The Observational Study of Asthma Control and Outcomes was a survey of patients with persistent asthma who were patients of Kaiser Colorado, including claims-based HRU. Patients completed the ACQ-5 three times during 1 year between April 2011 and June 2012. The ACQ-5 cutoffs that indicated control were assessed in cross-sectional analyses. Longitudinal changes in control were explored: controlled (ACQ-5 score <0.75), indeterminate (ACQ-5 score 0.75 to <1.5), not well controlled (ACQ-5 score 1.5 to <3.0), and very poorly controlled (ACQ-5 score ≥3.0). Analyses used generalized linear models with log link (expenditures) and negative binomial regression (HRU). RESULTS: There were 6,666 completed surveys (1,799 individuals completed all 3 survey waves). In the cross-sectional analyses, compared with an ACQ-5 score less than 0.5, individuals with ACQ-5 scores of 4 to 4.5 incurred 7.2 times the number of oral corticosteroid prescriptions, 4.3 times the number of emergency department visits, 6 times the number of inpatient visits, 10.4 times the number of asthma-specific emergency department visits, 4.58 times the number of asthma-specific inpatient visits, and $2,892 more in all-cause and $1,877 in asthma-specific expenditures during 4 months. In the longitudinal change analyses, individuals who improved from an ACQ-5 of 3.0 or greater to less than 0.75 incurred $6,023 less in asthma-specific expenditures during 4 months than those remaining at an ACQ-5 score of 3.0 or higher. CONCLUSION: Results provide preliminary economic data on possible control cutoffs for the ACQ-5. Improving asthma control over time may result in significant savings that may justify financial investments designed to improve control.

Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

BACKGROUND: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials. METHODS: A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD). All interview transcript data were coded using ATLAS.ti software for content analysis. RESULTS: Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively. The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement. During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %). A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD. Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand. The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary. CONCLUSIONS: This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing.