Preferences for potential benefits and risks for gene therapy in the treatment of sickle cell disease.

Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death, and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and 1 patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (ie, higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of ≥10%. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the increased risk tolerance, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by >50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.

Adaptation of the WOMAC for Use in a Patient Preference Study.

OBJECTIVES: To adapt a patient-reported outcome (PRO) measure, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), into efficacy attributes for a discrete choice experiment (DCE) survey designed to quantify the relative importance of endpoints commonly used in knee osteoarthritis (KOA) trials. METHODS: The adaptation comprised four steps: (1) selecting domains of interest; (2) determining presentation and framing of selected attributes; (3) determining attribute levels; and (4) developing choice tasks. This process involved input from multiple stakeholders, including regulators, health preference researchers, and patients. Pretesting was conducted to evaluate if patients comprehended the adapted survey attributes and could make trade-offs among them. RESULTS: The WOMAC pain and function domains were selected for adaption to two efficacy attributes. Two versions of the discrete choice experiment (DCE) instrument were created to compare efficacy using (1) total domain scores and (2) item scores for "walking on a flat surface." Both attributes were presented as improvement from baseline scores by levels of 0%, 30%, 50%, and 100%. Twenty-six participants were interviewed in a pretest of the instrument (average age 60 years; 58% female; 62% had KOA for ≥ 5 years). The participants found both versions of attributes meaningful and relevant for treatment decision-making. They demonstrated willingness and ability to tradeoff improvements in pain and function separately, though many perceived them as inter-related. CONCLUSIONS: This study adds to the growing literature regarding adapting PRO measures for patient preference studies. Such adaptation is important for designing a preference study that can incorporate a clinical trial's outcomes with PRO endpoints.

Quantitative Benefit-Risk Assessment in Medical Product Decision Making: A Good Practices Report of an ISPOR Task Force.

Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process. First, research question formulation needs to identify the needs of decision makers and requirements for preference data and specify the role of external experts. Second, the formal analysis model should be developed by selecting benefit and safety endpoints while eliminating double counting and considering attribute value dependence. Third, preference elicitation method needs to be chosen, attributes framed appropriately within the elicitation instrument, and quality of the data should be evaluated. Fourth, analysis may need to normalize the preference weights, base-case and sensitivity analyses should be conducted, and the effect of preference heterogeneity analyzed. Finally, results should be communicated efficiently to decision makers and other stakeholders. In addition to detailed recommendations, we provide a checklist for reporting qBRAs developed through a Delphi process conducted with 34 experts.

Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis.

OBJECTIVES: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo. METHODS: We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). RESULTS: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. CONCLUSION: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.

A Versatile and Scalable Platform That Streamlines Data Collection for Patient-Centered Studies: Usability and Feasibility Study.

BACKGROUND: The Food and Drug Administration Center for Biologics Evaluation and Research (CBER) established the Biologics Effectiveness and Safety (BEST) Initiative with several objectives, including the expansion and enhancement of CBER's access to fit-for-purpose data sources, analytics, tools, and infrastructures to improve the understanding of patient experiences with conditions related to CBER-regulated products. Owing to existing challenges in data collection, especially for rare disease research, CBER recognized the need for a comprehensive platform where study coordinators can engage with study participants and design and deploy studies while patients or caregivers could enroll, consent, and securely participate as well. OBJECTIVE: This study aimed to increase awareness and describe the design, development, and novelty of the Survey of Health and Patient Experience (SHAPE) platform, its functionality and application, quality improvement efforts, open-source availability, and plans for enhancement. METHODS: SHAPE is hosted in a Google Cloud environment and comprises 3 parts: the administrator application, participant app, and application programming interface. The administrator can build a study comprising a set of questionnaires and self-report entries through the app. Once the study is deployed, the participant can access the app, consent to the study, and complete its components. To build SHAPE to be scalable and flexible, we leveraged the open-source software development kit, Ionic Framework. This enabled the building and deploying of apps across platforms, including iOS, Android, and progressive web applications, from a single codebase by using standardized web technologies. SHAPE has been integrated with a leading Health Level 7 (HL7®) Fast Healthcare Interoperability Resources (FHIR®) application programming interface platform, 1upHealth, which allows participants to consent to 1-time data pull of their electronic health records. We used an agile-based process that engaged multiple stakeholders in SHAPE's design and development. RESULTS: SHAPE allows study coordinators to plan, develop, and deploy questionnaires to obtain important end points directly from patients or caregivers. Electronic health record integration enables access to patient health records, which can validate and enhance the accuracy of data-capture methods. The administrator can then download the study data into HL7® FHIR®-formatted JSON files. In this paper, we illustrate how study coordinators can use SHAPE to design patient-centered studies. We demonstrate its broad applicability through a hypothetical type 1 diabetes cohort study and an ongoing pilot study on metachromatic leukodystrophy to implement best practices for designing a regulatory-grade natural history study for rare diseases. CONCLUSIONS: SHAPE is an intuitive and comprehensive data-collection tool for a variety of clinical studies. Further customization of this versatile and scalable platform allows for multiple use cases. SHAPE can capture patient perspectives and clinical data, thereby providing regulators, clinicians, researchers, and patient advocacy organizations with data to inform drug development and improve patient outcomes.

Psychometric Validation of the EQ-5D-3L in Patients with Nontuberculous Mycobacterial (NTM) Lung Disease Caused by Mycobacterium avium Complex (MAC).

PURPOSE: This analysis evaluated the psychometric properties of the EQ-5D-3L among patients with Mycobacterium avium complex lung disease (MAC-LD). METHODS: Data from the Phase III CONVERT trial were analyzed. Study measures including the EQ-5D-3L, St. George's Respiratory Questionnaire (SGRQ), the 6-minute walk test (6MWT), and percent predicted forced expiratory volume in 1 second (ppFEV1) were collected at baseline, month 3 (M3), month 4 (M4; only 6MWT), and month 6 (M6). Item characteristics and validity were evaluated at baseline. Test-retest reliability was assessed using intraclass correlation coefficients (ICC) and a weighted kappa statistic among a subgroup of stable patients. Validity was tested by evaluating correlations of the EQ-5D-3L index/visual analogue scale (VAS) scores with SGRQ and 6MWT and comparing mean index/VAS scores across known groups defined using 6MWT and ppFEV1. Responsiveness of the EQ-5D-3L was assessed using 6MWT, SGRQ, ppFEV1, and culture conversion as anchors. RESULTS: The index score was subject to ceiling effects, with 32.6% of patients reporting perfect health at baseline. ICCs for the index (0.80) and VAS (0.85) scores and weighted kappas for the domains (0.5-0.72) indicated adequate test-retest reliability. Correlations between the index/VAS scores and related domains of the SGRQ and 6MWT were as hypothesized (0.31-0.62), and the mean index/VAS scores were significantly different between the 6MWT and ppFEV1 known groups (p<0.05), supporting the validity of the EQ-5D-3L. No evidence was found supporting the responsiveness of the EQ-5D-3L to changes in any of the anchors. CONCLUSION: EQ-5D-3L exhibited evidence of validity and reliability but poor responsiveness to clinically meaningful changes in patients with MAC-LD.

Patient and caregiver preferences for haemophilia A treatments: A discrete choice experiment.

INTRODUCTION: Long-acting products are changing the haemophilia A treatment landscape by giving patients and caregivers treatment options with varying product attributes. AIM: A discrete choice experiment (DCE) was used to elicit treatment attribute preferences among patients with haemophilia A and caregivers of children with haemophilia A. MATERIALS & METHODS: A survey of sociodemographics and preferences was completed by an online panel of adult patients with haemophilia A and caregivers of children (<18 years) with haemophilia A. The DCE included a series of questions in which respondents chose their preferred option from pairs of hypothetical treatment profiles with systematic variation in the levels of six attributes (safety concerns with too much clotting, bleed protection, dosing frequency, length of time the product has been approved for use, product type and joint health studies). Preference weights and relative attribute importance scores were estimated using random parameters logit models. RESULTS: One hundred and thirteen patients (mean age: 35.5 years) and 96 caregivers (mean age of child: 10.3 years) were included. For patients with haemophilia A, the top three attributes ranked from the most to least important were: (a) dosing frequency; (b) bleed protection; and (c) safety concerns with too much clotting. For caregivers of children with haemophilia A, the ranking was as follows: (a) safety concerns; (b) bleed protection; and (c) dosing. CONCLUSIONS: Patients with haemophilia A viewed dosing as the most important driver of treatment decision-making whereas caregivers of children with haemophilia A valued safety the most.

Patient and caregiver benefit-risk preferences for nonmetastatic castration-resistant prostate cancer treatment.

BACKGROUND: Recently approved second-generation androgen receptor inhibitors (SGARIs) for non-metastatic castration-resistant prostate cancer (nmCRPC) have similar efficacy but differ in safety profiles. We used a discrete choice experiment (DCE) to examine how nmCRPC patients and caregivers perceive the benefits versus risks of these new treatments. METHODS: An online DCE survey with 14 treatment choice questions was administered to nmCRPC patients and caregivers. Each choice question compared two hypothetical medication profiles varying in terms of 5 safety attributes (risk or severity of adverse events [AEs]: fatigue, skin rash, cognitive problems, serious fall, and serious fracture) and two efficacy attributes (duration of overall survival [OS] and time to pain progression). Random parameters logit models were used to estimate each attribute's relative importance. We also estimated the amounts of OS that respondents were willing to forego for a reduction in AEs. RESULTS: In total, 143 nmCRPC patients and 149 caregivers viewed the AEs in following order of importance (most to least): serious fracture, serious fall, cognitive problems, fatigue, and skin rash. On average, patients were willing to trade 5.8 and 4.0 months of OS to reduce the risk of serious fracture and fall, respectively, from 3% to 0%; caregivers were willing to trade 6.6 and 5.4 months of OS. CONCLUSIONS: nmCRPC patients and caregivers preferred treatments with lower AE burdens and were willing to forego OS to reduce the risk and severity of AEs. Our results highlight the importance of carefully balancing risks and benefits when selecting treatments in this relatively asymptomatic population.

Physician preferences for non-metastatic castration-resistant prostate cancer treatment.

BACKGROUND: Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. We used a discrete choice experiment to explore how United States physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC, a largely asymptomatic disease. METHODS: Treating physicians (n = 149) participated in an online survey that included 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied in terms of 5 safety and 2 efficacy attributes. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency, and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a random parameters logit model to estimate preference weights and importance scores for each attribute. We also estimated the amount of survival gain physicians were willing to trade for a reduction in specific AEs between treatment options. RESULTS: Physicians placed more importance on survival than on time to pain progression, and viewed a reduction in cognitive problems from severe to none, a reduction in risk of a serious fracture from 8% to none, and a reduction in fatigue from severe to none as the most important safety attributes. Physicians were willing to forego 9.1 and 6.6 months of OS, respectively, to reduce cognitive problems and fatigue from severe to mild-to-moderate. To reduce the risk of a serious fracture from 8 to 5% and 5% to none, physicians were willing to trade 3.9 and 5.3 months of OS, respectively. CONCLUSIONS: Physicians were willing to trade substantial amounts of survival to avoid AEs between hypothetical treatments. These results emphasize the importance of carefully balancing therapies' benefits and risks to ultimately optimize the overall quality of nmCRPC patients' survival. Nonetheless, it is noted that the results from the study sample of 149 physicans may not be representative of the viewpoints of all nmCRPC-treating physicians.

Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir.

PURPOSE: People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. PATIENTS AND METHODS: PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. RESULTS: There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. CONCLUSION: This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. CLINICALTRIALSGOV IDENTIFIER: NCT02358044.

Caregivers' Priorities and Observed Outcomes of Attention-Deficit Hyperactivity Disorder Medication for Their Children.

OBJECTIVE: To document variability among caregivers' priorities when considering medication to treat their Children's attention-deficit hyperactivity disorder (ADHD) and explore associations between these priorities and medication-related improvements. METHODS: Caregivers of children, ages 4 to 14 years, diagnosed with ADHD were recruited from outpatient clinics and support groups across Maryland. A survey gathered data on caregiver-reported concerns when considering ADHD medication, demographic characteristics, and observed and desired improvements in their child's ADHD. A validated Best-Worst Scaling instrument assessed priorities among 16 concerns when considering ADHD medication. Latent class analysis identified subgroups with similar ADHD medication concerns. Differences in self-reported medication-related improvements were examined across subgroups. RESULTS: The 184 participants (mean = 42 yrs) were primarily the biological mother, 68% white and 25% black. Their children were mostly male (73%) and using medication (81%). Overall, the most important ADHD medication concerns were the child becoming a successful adult (p < 0.0001), school behavior improvements (p < 0.0001), and better grades (p < 0.0001). Others thinking badly of the child was a significantly less important concern (p < 0.0001). Three subgroups were identified: short-term outcomes-oriented group (39%), long-term outcomes-oriented group (37%), and side effects/safety-oriented group (27%). Relative to the other 2 groups, a smaller proportion of the side effects/safety-oriented group desired these improvements (p < 0.2618). CONCLUSION: Most caregivers prioritize short- and long-term outcomes when considering ADHD medication. However, those most concerned with long- or short-term outcomes tended to desire additional improvements in their child's ADHD.

Caregiver Treatment Preferences for Children with a New Versus Existing Attention-Deficit/Hyperactivity Disorder Diagnosis.

OBJECTIVES: Parental experiences with managing their child's attention-deficit/hyperactivity disorder (ADHD) can influence priorities for treatment. This study aimed to identify the ADHD management options caregivers most prefer and to determine if preferences differ by time since initial ADHD diagnosis. METHODS: Primary caregivers (n = 184) of a child aged 4-14 years old in care for ADHD were recruited from January 2013 through March 2015 from community-based pediatric and mental health clinics and family support organizations across the state of Maryland. Participants completed a survey that included child/family demographics, child clinical treatment, and a Best-Worst Scaling (BWS) experiment to elicit ADHD management preferences. The BWS comprised 18 ADHD management profiles showing seven treatment attributes, where the best and worst attribute levels were selected from each profile. A conditional logit model using effect-coded variables was used to estimate preference weights stratified by time since ADHD diagnosis. RESULTS: Participants were primarily the mother (84%) and had a college or postgraduate education (76%) with 75% of the children on stimulant medications. One-on-one caregiver behavior training, medication use seven days a week, therapy in a clinic, and an individualized education program were most preferred for managing ADHD. Aside from caregiver training and monthly out-of-pocket costs, caregivers of children diagnosed with ADHD for less than two years prioritized medication use lower than other care management attributes and caregivers of children diagnosed with ADHD for two or more years preferred school accommodations, medication, and provider specialty. CONCLUSIONS: Preferences for ADHD treatment differ based on the duration of the child's ADHD. Acknowledging that preferences change over the course of care could facilitate patient/family-centered care planning across a range of resources and a multidisciplinary team of professionals.

A Latent Class Analysis to Identify Variation in Caregivers' Preferences for their Child's Attention-Deficit/Hyperactivity Disorder Treatment: Do Stated Preferences Match Current Treatment?

OBJECTIVES: To investigate variation in caregiver preferences for their child's attention-deficit/hyperactivity disorder (ADHD) care and to determine if their stated preferences align with current care management. METHODS: Caregivers of a child aged 4-14 years and in care for ADHD were recruited from pediatric outpatient clinics and advocacy groups across the state of Maryland. Participants completed a survey collecting demographics, the child's treatment, and caregiver preferences-elicited using a best-worst scaling experiment (case 2). Latent class analysis was used to identify distinct preference segments and bivariate analyses were used to compare the association between segment membership with what the child was currently receiving for their ADHD. RESULTS: Participants (n = 184) were predominantly White (68%) and the child's mother (84%). Most children had ADHD for 2 or more years (79%). Caregiver preferences were distinguished by two segments: continuous medication (36%) and minimal medication (64%). The two groups had very different preferences for when medication was administered (p < 0.001), but they had similar preferences for provider-oriented and non-medication interventions (p > 0.05 for the caregiver behavior training, provider communication, provider specialty, and out-of-pocket costs). One third of the sample did not receive the preferred individualized education program and 42% of the minimal medication group reported using medication 7 days a week all year round. CONCLUSIONS: Although behavior management training and school accommodations aspects of an ADHD care plan are more important to caregivers than evidence-based medication, fewer families had access to educational accommodations. Further research is needed to clarify how stated preferences for care align with treatments used in actual practice settings.

Assessment of an Expanded Functional Disability Scale for Older Adults With Diabetes.

Although prior literature has shown the plausibility of combining the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) items to form an expanded scale for measuring the degree of functional decline, this has not been shown in older adults with diabetes who are disproportionately affected by functional disability. Using the 2009 Medicare Current Beneficiary Survey data, we evaluated the factor structure of the pooled ADL and IADL items. Based on our study comprising 2,158 community-dwelling older adults (≥65 years) with diabetes, the unidimensional model exhibited good fit. Despite well-fitting indices, high correlations were observed between the latent constructs (>.70) of the multi-factor models, suggesting a lack of discriminant validity. These findings provide empirical support for a combined scale that can comprehensively and efficiently characterize the extent of functional disability in older adults with diabetes for research, risk adjustment, and evaluation in patient-centered medical homes.

Comparison of the Charlson Comorbidity Index derived from self-report and medical record review in Asian patients with rheumatic diseases.

The aim of the study was to compare the agreement between self-report Charlson Comorbidity Index (SR-CCI) and the medical record-based CCI (MR-CCI) and to examine the impact of both instruments on health-related quality of life (HRQoL) amongst Asian patients with rheumatic diseases. This cross-sectional study surveyed a convenience sample of patients seen at rheumatology specialty outpatient clinics. Patients completed the SR-CCI and Short Form 36, while two research assistants completed the MR-CCI. Item-level agreement between the SR-CCI and MR-CCI was evaluated using kappa coefficients. Adjusted linear regression models evaluated the independent effect of the SR-CCI/MR-CCI on HRQoL. The study included 301 patients (median age 51, range 21-79, 61.5 % female, 68.8 % Chinese, 17.6 % Indian, 6.0 % Malay). Kappa statistics for cerebrovascular disease (0.433), chronic pulmonary disease (0.509), connective tissue disease/rheumatoid arthritis (0.506), ulcer disease (0.461), and tumour (0.541) reflected moderate agreement between the SR-CCI and MR-CCI (all p < 0.0001). There was substantial agreement in the reporting of diabetes (0.764, p < 0.0001) but poor/fair agreement for that of myocardial infarction (0.359, p < 0.0001) and diabetes with end-organ damage (0.189, p = 0.0002). Increases in SR-CCI were associated with significant reductions in both physical (ß coefficient -2.56, p < 0.0001) and mental HRQoL (ß coefficient -1.24, p = 0.044). However, such associations were not observed with the MR-CCI. The SR-CCI demonstrated moderate concordance with the MR-CCI, and the SR-CCI but not MR-CCI scores were associated with lower HRQoL. Assessment of comorbidities amongst rheumatology patients remains complex, and more efficient methods of quantifying these conditions are needed for clinical and research purposes.

Pulmonologist involvement, stage-specific treatment, and survival in adults with non-small cell lung cancer and chronic obstructive pulmonary disease.

RATIONALE: Up to 80% of patients with lung cancer have comorbid chronic obstructive pulmonary disease (COPD). Many of them are poor candidates for stage-specific lung cancer treatment due to diminished lung function and poor functional status, and many forego treatment. The negative effect of COPD may be moderated by pulmonologist-guided management. OBJECTIVES: This study examined the association between pulmonologist management and the probability of receiving the recommended stage-specific treatment modality and overall survival among patients with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS: Early- and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance, Epidemiology, and End Results tumor registry data linked to Medicare claims. Study outcomes included receipt of recommended stage-specific treatment (surgical resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC [advNSCLC]) and overall survival. Pulmonologist management was considered present if one or more Evaluation and Management visit claims with pulmonologist specialty were observed within 6 months after NSCLC diagnosis. Stage-specific multivariate logistic regression tested association between pulmonologist management and treatment received. Cox proportional hazard models examined the independent association between pulmonologist care and mortality. Two-stage residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted for potential confounding based on unobserved factors or measurement error. MEASUREMENTS AND MAIN RESULTS: The cohorts included 5,488 patients with early-stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD. Pulmonologist management was recorded for 54.9% of patients with early stage NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist involvement, 58.5% of patients with early NSCLC received surgical resection, and 43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management post NSCLC diagnosis was associated with increased surgical resection rates (odds ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for advNSCLC. Pulmonologist management was also associated with reduced mortality risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS: Pulmonologist management had a positive association with rates of stage-specific treatment in both groups and overall survival in early-stage NSCLC. These results provide preliminary support for the recently published guidelines emphasizing the role of pulmonologists in lung cancer management.

A best-worst scaling experiment to prioritize caregiver concerns about ADHD medication for children.

OBJECTIVE: The objective of this feasibility study was to develop and pilot an instrument to elicit caregivers' priorities when initiating attention-deficit hyperactivity disorder (ADHD) medication for their child. METHODS: A best-worst scaling experiment was used to rank competing priorities when initiating ADHD medicine. Forty-six participants were recruited for a two-phase study involving survey development (phase 1, N=21) and the survey pilot (phase 2, N=25). Best-worst scores and 95% confidence intervals indicating the relative importance of 16 concerns were determined, and t tests were used to determine the scores' significance. RESULTS: The significance of best-worst scores for most concerns indicated that the choices were purposeful. Concerns about helping the child become a successful adult, having a doctor who addresses caregivers' concerns, and improving school behavior were ranked highest. CONCLUSIONS: The best-worst scaling method can elicit priorities for children's mental health treatment. Future work using this method will guide family-centered care.

Using Best-Worst Scaling to Measure Caregiver Preferences for Managing their Child's ADHD: A Pilot Study.

BACKGROUND: Management of attention-deficit/hyperactivity disorder (ADHD) is a trade-off between caregivers' concerns about the benefits versus the risks of evidence-based treatment. Few studies have used choice-based methods to assess what treatment attributes matter most to caregivers. OBJECTIVE: The aim was to develop and to pilot an instrument to elicit caregivers' preferences for evidence-based management of their child's ADHD. METHODS: Mixed methods were used to develop a Best-Worst Scaling (BWS) instrument, and quantitative methods were used to pilot the instrument. Primary caregivers of children with ADHD from two community organizations were recruited for the development (n = 21) and pilot (n = 37) phase. The instrument was a BWS case 2, where 18 management profiles are presented one at a time, with respondents indicating the one best and one worst feature of each profile. Profiles were developed using a main effects orthogonal array. The mean of best-minus-worse scores was estimated, and attribute importance was based on the sum of maximum minus minimum scores for each attribute. Feasibility of eliciting stated preferences was evaluated with t tests and 95 % confidence intervals. RESULTS: Seven attributes (medication, therapy, school, caregiver training, provider specialty, provider communication, and out-of-pocket costs) with three levels each were identified. All mean scores were significant except for pediatrician management of the child's ADHD (p = 0.089). Caregiver training had the highest relative importance, followed by medication and provider communication. CONCLUSIONS: The BWS instrument was a relatively simple measure, caregivers completed it independently, and it distinguished the relative importance of different attributes in managing a child's ADHD.

Construct validity and factor structure of survey-based assessment of cost-related medication burden.

BACKGROUND: Millions of Americans are burdened by out-of-pocket prescription costs. Although many survey measures have been developed to assess this burden, the construct validity and the factor structure of these instruments have not been rigorously assessed. OBJECTIVES: To characterize the factor structure and the construct validity of items assessing cost-related medication burden. METHODS: We applied exploratory factor and confirmatory factor analyses to the 2009 Medicare Current Beneficiary Survey, focusing on 10 items assessing cost-related mediation burden among a nationally representative sample of community-dwelling Medicare beneficiaries. The fit of competing models was compared using several indices. RESULTS: The study population (N=8777) was predominantly aged over 65 years (83.3%), female (54.4%), and white (84.3%). Two distinct factors were present for the medication cost-reduction strategies: (1) cost-related medication nonadherence and (2) drug-shopping behaviors, not directly impacting medication compliance. The two factors were moderately correlated (r=0.55), highlighting the presence of a 2 distinct but related constructs for cost-related medication burden. An item assessing the use of mail or internet pharmacies did not load well on either factor and may not necessarily measure medication-related cost burden. An item assessing reduced spending on basic needs loaded strongly on the same factor with the cost-related medication nonadherence items, suggesting they together may represent extreme compensatory behaviors that may adversely affect health outcomes. CONCLUSIONS: Two distinct constructs were derived from these items examining cost-related medication burden. Although cost-related medication burden is often associated with nonadherence, drug-shopping behaviors that do not directly impact adherence are also important measure of this burden.

Disease patterns of rheumatology outpatients seen in a tertiary hospital serving a multi-ethnic, urban Asian population in Singapore.

AIMS: To describe the spectrum of diseases seen in an outpatient setting in the Singapore General Hospital, the largest tertiary referral centre in Singapore. METHODS: In this cross-sectional study, medical records of patients scheduled for an appointment at the rheumatology specialist outpatient clinics over a 4-month period (10 August 2010-31 December 2010) were reviewed. Primary diagnoses documented by the attending physician at the latest visit were recorded. RESULTS: Among 4180 patients (29.5% male; mean [SD] age: 53.5 [15.1] years; 77.0% Chinese, 8.0% Malay, 8.8% Indian and 6.2% others), the spectrum of diseases seen was as follows [disease - definite n (%), probable n (%)]: Arthritis: rheumatoid arthritis - 958 (22.9%), 68 (1.6%); osteoarthritis - 452 (10.8%), 39 (0.9%); crystal arthritis - 417 (10.0%), 18 (0.4%); spondyloarthritis - 227 (5.4%), 61 (1.5%); psoriatic arthritis - 158 (3.8%), 9 (0.2%); other inflammatory arthritis - 153 (3.7%), 94 (2.2%); Connective tissues diseases: systemic lupus erythematosus - 412 (9.9%), 26 (0.6%); vasculitis - 105 (2.5%), 22 (0.5%); Sjögren's syndrome - 81 (1.9%), 32 (0.8%); overlap syndromes - 73 (1.8%); scleroderma - 50 (1.2%), 4 (0.1%); undifferentiated connective tissue diseases - 45 (1.1%), 106 (2.5%); myositis - 41 (1.0%), 12 (0.3%); antiphospholipid syndrome - 22 (0.5%), 7 (0.2%); polymyalgia rheumatica - 16 (0.4%); Others: soft tissue rheumatism - 155 (3.7%); osteoporosis - 61 (1.5%); other non-rheumatologic conditions - 189 (4.5%); other rheumatologic conditions - 67 (1.6%). CONCLUSION: Rheumatoid arthritis, osteoarthritis and crystal arthritis were the three most common rheumatological diseases seen in a tertiary referral centre serving a multi-ethnic urban Asian population in Singapore.