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Background: The Paediatric Quality of life Inventory (PedsQL TM ) Generic Core Scales and the Child Health Utilities 9 Dimensions (CHU9D) are two paediatric health-related quality of life (HRQoL) measures commonly used in overweight and obesity research. However, no studies have comprehensively established the psychometric properties of these instruments in the context of paediatric overweight and obesity. The aim of this study was to assess the reliability, acceptability, validity and responsiveness of the PedsQL and the CHU9D in the measurement of HRQoL among children and adolescents living with overweight and obesity., Subjects/methods: Subjects were 6544 child participants of the Longitudinal Study of Australian Children, with up to 3 repeated measures of PedsQL and CHU9D and aged between 10 and 17 years. Weight and height were measured objectively by trained operators, and weight status determined using World Health Organisation growth standards. We examined reliability, acceptability, known group and convergent validity and responsiveness, using recognised methods., Results: Both PedsQL and CHU9D demonstrated good internal consistency reliability, and high acceptability. Neither instrument showed strong convergent validity, but PedsQL appears to be superior to the CHU9D in known groups validity and responsiveness. Compared with healthy weight, mean (95%CI) differences in PedsQL scores for children with obesity were: boys -5.6 (-6.2, -4.4); girls -6.7 (-8.1, -5.4) and differences in CHU9D utility were: boys -0.02 (-0.034, -0.006); girls -0.035 (-0.054, -0.015). Differences in scores for overweight compared with healthy weight were: PedsQL boys -2.2 (-3.0, -1.4) and girls -1.3 (-2.0, -0.6) and CHU9D boys: no significant difference; girls -0.014 (-0.026, -0.003)., Conclusion: PedsQL and CHU9D overall demonstrated good psychometric properties, supporting their use in measuring HRQoL in paediatric overweight and obesity. CHU9D had poorer responsiveness and did not discriminate between overweight and healthy weight in boys, which may limit its use in economic evaluation., (© 2023. The Author(s).)

Objectives: Co-creation of diabetes and obesity prevention with remote communities allows local contextual factors to be included in the design, delivery, and evaluation of disease prevention efforts. The Indian Ocean Territories (IOT) comprise the Christmas (CI) and Cocos Keeling Islands (CKI) and are remote Australian external territories located northwest of the mainland. We present results of a co-design process conducted with residents of IOT using realist inquiry and system mapping., Methods: Interviews with 33 community members (17 CI, 14 CKI, 2 off Islands) on causes and outcomes of diabetes (2020/21) comprising community representatives, health services staff, dietitians, school principals and government administrators. Interviews were used to create causal loop diagrams representing the causes of diabetes in the IOT. These diagrams were used in a participatory process to identify existing actions to address diabetes, identify areas where more effort would be valuable in preventing diabetes, and to described and prioritize actions based on feasibility and likely impact., Findings: Interviews identified 31 separate variables categorized into four themes (structural, food, knowledge, physical activity). Using causa loop diagrams, community members developed 32 intervention ideas that included strengthening healthy behaviors like physical activity, improving access to healthy and culturally appropriate foods, and overcoming the significant cost and availability limitations imposed by remoteness and freight costs. Interventions included relatively unique Island issues (e.g., freight costs, limited delivery timing), barriers to healthy food (e.g., limited fresh food availability), physical activity (e.g., transient workforce) and knowledge (e.g., multiple cultural backgrounds and language barriers, intergenerational knowledge)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Allender, Munira, Bourke and Lancsar.)

Background/aims: Discrete choice experiments (DCEs) with either duration included an attribute or with dead included as an option can be used as a stand-alone approach to value health states. This paper reports on a DCE with both of these features to develop an EQ-5D-5L value set for Australia., Methods: A DCE was undertaken using a large Australian panel of internet respondents, from which a sample of more than 4000 Australian adults was chosen, stratified to be population representative on age and gender. The DCE contained 500 choice triplets, with two EQ-5D-5L health states with duration, and dead as the third option. Each respondent answered 12 choice sets from the 500, stating both the best and worst options from the three available. The design was constructed to estimate a utility algorithm with main effects plus some key interaction terms. A variety of approaches to parameterising interactions, and to anchoring the value set on the required 0-1 scale, were tested. A preferred Australian adult utility algorithm for use in cost-utility analysis was then generated., Results: In total, 4477 people completed at least one choice set and were included in the analysis. The results reflected the monotonic structure of the EQ-5D-5L, in that moving from no problems to extreme problems led to worsening utility in each dimension. Inclusion of interaction terms demonstrates that the disutility of the first dimension moving to a poor level (defined as either level 5, or level 4 or 5) had a large impact, but subsequent dimensions moving to a poor level had a relatively smaller disutility., Discussion: This work develops a value set for the EQ-5D-5L in Australia, and also provides a range of methodological insights which can inform future work using a stand-alone DCE to value health in other countries., (© 2023. The Author(s).)

In this multi-center longitudinal cohort study conducted in Australia and New Zealand, we assessed the trajectories of health-related quality of life (HRQoL) in children with chronic kidney disease (CKD) over time. A total of 377 children (aged 6-18 years) with CKD stages 1-5 (pre-dialysis), dialysis, or transplant, were followed biennially for four years. Multi Attribute Utility (MAU) scores of HRQoL were measured at baseline and at two and four years using the McMaster Health Utilities Index Mark 3 tool, a generic multi-attribute, preference-based system. A multivariable linear mixed model was used to assess the trajectories of HRQoL over time in 199 children with CKD stage 1-5, 43 children receiving dialysis and 135 kidney transplant recipients. An interaction between CKD stage at baseline and follow-up time indicated that the slopes of the HRQoL scores differed between children by CKD stage at inception. Over half of the cohort on dialysis at baseline had received a kidney transplant by the end of year four and the MAU scores of these children increased by a meaningful amount averaging 0.05 (95% confidence interval 0.01 to 0.09) per year in comparison to those who were transplant recipients at baseline. The mean difference between baseline and year two MAU scores was 0.09 (95% confidence interval -0.05, 0.23), (Cohen's d effect size 0.31). Thus, improvement in HRQoL over time of children on dialysis at baseline was likely to have been driven by their transition from dialysis to transplantation. Additionally, children with CKD stage 1-5 and transplant recipients at baseline had no changes in their disease stage or treatment modality and experienced stable HRQoL over time., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: In line with affordability and equity principles, Medicare-Australia's universal health care program-has measures to contain out-of-pocket (OOP) costs, particularly for lower income households. This study examined the distribution of OOP costs for Medicare-subsidised out-of-hospital services and prescription medicines in Australian households, according to their ability to pay., Methods: OOP costs for out-of-hospital services and medicines in 2017-18 were estimated for each household, using 2016 Australian Census data linked to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefit Scheme (PBS) claims. We derived household disposable income by combining income information from the Census linked to income tax and social security data. We quantified OOP costs as a proportion of equivalised household disposable income and calculated Kakwani progressivity indices (K)., Results: Using data from 82% (n = 6,830,365) of all Census private households, OOP costs as a percentage of equivalised household disposable income decreased from 1.16% in the poorest decile to 0.63% in the richest decile for MBS services, and from 1.35% to 0.35% for PBS medicines. The regressive trend was less pronounced for MBS services (K = -0.06), with percentage OOP cost relatively stable between the 2nd and 9th income deciles; while percentage OOP cost decreased with increasing income for PBS medicines (K = -0.24)., Conclusion: OOP costs for out-of-hospital Medicare services were mildly regressive while those for prescription medicines were distinctly regressive. Actions to reduce inequity in OOP costs, particularly for medicines, should be considered., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This paper reports on the valuation of the classification system for the Quality-of-Life Aged Care Consumers (QOL-ACC) instrument using a discrete choice experiment (DCE) with duration with a large sample of older people receiving aged care services., Methods: A DCE with 160 choice sets of two quality-of-life state-survival duration combinations blocked into 20 survey versions, with eight choice sets in each version, was designed and administered through an on-line survey to older Australians receiving aged care services in home and via interviewer facilitation with older people in residential aged care settings. Model specifications investigating preferences with respect to survival duration and interactions between QOL-ACC dimension levels were estimated. Utility weights were developed, with estimated coefficients transformed to the 0 (being dead) to 1 (full health) scale to generate a value set suitable for application in quality assessment and for the calculation of quality-adjusted life-years for use in economic evaluation., Results: In total, 953 older people completed the choice experiment with valid responses. The estimation results from econometric model specifications indicated that utility increased with survival duration and decreased according to quality-of-life impairment levels. An Australian value set (range - 0.56 to 1.00) was generated for the calculation of utilities for all QOL-ACC states., Conclusion: The QOL-ACC is unique in its focus on measuring and valuing quality of life from the perspective of older people themselves, thereby ensuring that the preferences of aged care service users are the primary focus for quality assessment and economic evaluation., (© 2022. The Author(s).)

Despite unprecedented progress in developing COVID-19 vaccines, global vaccination levels needed to reach herd immunity remain a distant target, while new variants keep emerging. Obtaining near universal vaccine uptake relies on understanding and addressing vaccine resistance. Simple questions about vaccine acceptance however ignore that the vaccines being offered vary across countries and even population subgroups, and differ in terms of efficacy and side effects. By using advanced discrete choice models estimated on stated choice data collected in 18 countries/territories across six continents, we show a substantial influence of vaccine characteristics. Uptake increases if more efficacious vaccines (95% vs 60%) are offered (mean across study areas = 3.9%, range of 0.6%-8.1%) or if vaccines offer at least 12 months of protection (mean across study areas = 2.4%, range of 0.2%-5.8%), while an increase in severe side effects (from 0.001% to 0.01%) leads to reduced uptake (mean = -1.3%, range of -0.2% to -3.9%). Additionally, a large share of individuals (mean = 55.2%, range of 28%-75.8%) would delay vaccination by 3 months to obtain a more efficacious (95% vs 60%) vaccine, where this increases further if the low efficacy vaccine has a higher risk (0.01% instead of 0.001%) of severe side effects (mean = 65.9%, range of 41.4%-86.5%). Our work highlights that careful consideration of which vaccines to offer can be beneficial. In support of this, we provide an interactive tool to predict uptake in a country as a function of the vaccines being deployed, and also depending on the levels of infectiousness and severity of circulating variants of COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Governments and health insurers often make funding decisions based on health gains from randomised controlled trials. These decisions are inherently uncertain because health gains in trials may not translate to practice owing to differences in the population, treatment use and setting. Post-market analysis of real-world data can provide additional evidence but estimates from standard matching methods may be biased when unobserved characteristics explain whether a patient is treated and their outcomes. We propose a new untreated matching approach that can reduce this bias. Our approach utilises the outcomes of contemporaneous untreated patients to improve the matching of treated and historical control patients. We assess the performance of this new approach compared to standard matching using a simulation study and demonstrate the steps required using a funding decision for prostate cancer treatments in Australia. Our simulation study shows that our new matching approach eliminates nearly all bias when unobserved treatment selection is related to outcomes, and outperforms standard matching in most scenarios. In our empirical example, standard matching overestimated survival by 15% (95% confidence interval 2-34) compared to our untreated matching approach. The health gains estimated using our approach were slightly lower than expected based on the trial evidence, but we also found evidence that in practice prescribers ceased prior therapies earlier, treated a more vulnerable population and continued treatment for longer. Our untreated matching approach offers researchers a new tool for reducing uncertainty in healthcare funding decisions using real-world data.

Background: Medication management in residential aged care facilities is an ongoing concern. Numerous studies have reported high rates of inappropriate prescribing and medication use in aged care facilities, which contribute to residents' adverse health outcomes. There is a need for new models of care that enhance inter-disciplinary collaboration between residential aged care facility staff and healthcare professionals, to improve medication management. Pilot research has demonstrated the feasibility and benefits of integrating a pharmacist into the aged care facility team to improve the quality use of medicines. This protocol describes the design and methods for a cluster randomised controlled trial to evaluate the outcomes and conduct economic evaluation of a service model where on-site pharmacists are integrated into residential aged care facility healthcare teams to improve medication management., Methods: Intervention aged care facilities will employ on-site pharmacists to work as part of their healthcare teams 2 to 2.5 days per week for 12 months. On-site pharmacists, in collaboration with facility nurses, prescribers, community pharmacists, residents and families will conduct medication management activities to improve the quality use of medicines. Aged care facilities in the control group will continue usual care. The target sample size is 1188 residents from a minimum of 13 aged care facilities. The primary outcome is the appropriateness of prescribing, measured by the proportion of residents who are prescribed at least one potentially inappropriate medicine according to the 2019 Beers Criteria. Secondary outcomes include hospital and emergency department presentations, fall rates, prevalence and dose of antipsychotics and benzodiazepines, Anticholinergic Cognitive Burden Score, staff influenza vaccination rate, time spent on medication rounds, appropriateness of dose form modification and completeness of resident's allergy and adverse drug reaction documentation. A cost-consequence and cost-effectiveness analysis will be embedded in the trial., Discussion: The results of this study will provide information on clinical and economic outcomes of a model that integrates on-site pharmacists into Australian residential aged care facilities. The results will provide policymakers with recommendations relevant to further implementation of this model., Trial Registration: ACTRN12620000430932 . Registered on 1 April 2020 with ANZCTR.

Objectives: The objective of this study was to investigate the degree of inconsistency in quality-of-life attribute preference orderings generated via successive best-worst scaling (a form of ranking whereby the respondent chooses the best and worst attributes from a choice set, these attributes are then eliminated and the best and worst attributes from the reduced choice set are then chosen and this process is continued until all presented attributes are eliminated) and conventional ranking methods (whereby the respondent chooses the best, second best and third best from a choice set until all presented attributes are eliminated)., Methods: An on-line survey was developed for administration to two general population samples comprising younger people (aged 18-64 years) and older people (aged 65 years and above). Data were analysed in STATA through an empirical examination of the relative level of choice inconsistency (randomness in responses or the variability in choice outcomes not explained by attributes and their associated preference weights) for successive best-worst in comparison with the conventional ranking method for the younger and older person samples., Results: For the younger person sample, both methods were found to be similarly consistent. In contrast, for the older person sample, ranking performed relatively worse than best-worst scaling with more inconsistent responses (tau = 0.515, p < 0.01)., Conclusions: These findings lend some support to the hypothesis initially propagated by the developers of best-worst scaling that it is a comparatively easier choice task for respondents to undertake than a traditional ranking task.

The oft-applied assumption in the use of Quality Adjusted Life Years (QALYs) in economic evaluation, that all QALYs are valued equally, has been questioned from the outset. The literature has focused on differential values of a QALY based on equity considerations such as the characteristics of the beneficiaries of the QALYs. However, a key characteristic which may affect the value of a QALY is the type of QALY itself. QALY gains can be generated purely by gains in survival, purely by improvements in quality of life, or by changes in both. Using a discrete choice experiment and a new methodological approach to the derivation of relative weights, we undertake the first direct and systematic exploration of the relative weight accorded different QALY types and do so in the presence of equity considerations; age and severity. Results provide new evidence against the normative starting point that all QALYs are valued equally., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose and Setting: Despite the label "generic" health state utility instruments (HSUIs), empirical evidence shows that different HSUIs generate different estimates of Health-Related Quality of Life (HRQoL) in the same person. Once a HSUI is used to generate a QALY, the difference between HSUIs is often ignored, and decision-makers act as if 'a QALY is a QALY is a QALY'. Complementing evidence that different generic HSUIs produce different empirical values, this study addresses an important gap by exploring how HSUIs differ, and processes that produced this difference. 15 developers of six generic HSUIs used for estimating the QOL component of QALYs: Quality of Well-Being (QWB) scale; 15 Dimension instrument (15D); Health Utilities Index (HUI); EuroQol EQ-5D; Short Form-6 Dimension (SF-6D), and the Assessment of Quality of Life (AQoL) were interviewed in 2012-2013., Principal Findings: We identified key factors involved in shaping each instrument, and the rationale for similarities and differences across measures. While HSUIs have a common purpose, they are distinctly discrete constructs. Developers recalled complex developmental processes, grounded in unique histories, and these backgrounds help to explain different pathways taken at key decision points during the HSUI development. The basis for the HSUIs was commonly not equivalent conceptually: differently valued concepts and goals drove instrument design and development, according to each HSUI's defined purpose. Developers drew from different sources of knowledge to develop their measure depending on their conceptualisation of HRQoL., Major Conclusions/contribution to Knowledge: We generated and analysed first-hand accounts of the development of the HSUIs to provide insight, beyond face value, about how and why such instruments differ. Findings enhance our understanding of why the six instruments developed the way they did, from the perspective of key developers of those instruments. Importantly, we provide additional, original explanation for why a QALY is not a QALY is not a QALY., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Evidence surrounding utilities for health states, derived either directly from the application of preference-based valuation methods or indirectly from the application of preference-based quality of life instruments, is increasingly being utilised to inform the cost-effectiveness of child health interventions. Proxy (parent or health professional) assessments are common in this area. This study sought to investigate the degree of convergence in childhood utilities generated directly or indirectly within dyad child and proxy assessments., Methods: A systematic literature review was conducted following PRISMA guidelines. A comprehensive literature search strategy conducted across six search engines (PubMed, Embase, Web of Science, PsychoINFO, EconLit, CINAHL and Cochrane Library). Original peer-reviewed articles that reported utilities derived directly or indirectly using simultaneous dyad child and proxy assessments were extracted. Mean and median utilities, correlation coefficients and levels of agreement were extracted, catalogued and assessed., Results: A total of 35 studies that reported utilities for two or more respondent types were identified. Of these, 29 studies reported dyad childhood self-report and proxy utilities whilst six studies reported levels of agreement and/or correlations only without documenting overall utilities. Proxy assessment was most often conducted by parents with the HUI3 representing the most commonly applied instrument across a range of health conditions. The utilities derived from child and parent proxy assessment were bidirectional with parental proxies tending to underestimate and health professional proxies tending to overestimate relative to child self-reports. Inter-rater agreement between child self-reports and parent-proxy reports were poorer for more subjective attributes (cognition, emotion and pain), relative to physical attributes (mobility, self-care, speech, vision) of health-related quality of life., Conclusions: Childhood utilities derived from children or proxies are not interchangeable. The choice of self or proxy assessor may have potentially significant implications for economic evaluations of child health interventions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An increase in sugar-sweetened beverage (SSB) prices has been suggested to reduce SSB intake to improve population health. Using a discrete choice experiment, we tested the effect of price changes on beverage choices in an online hypothetical convenience store setting amongst 1,008 Australian adults in May to June 2016. From this we calculated pre-packaged beverage price elasticities overall and for health policy-target consumer subgroups; and identified consumer subgroups likely to be most reactive to beverage price changes. Using mixed logit analysis, we found similar price elasticities for age, gender and income groups. More frequent SSB consumers tended to be less sensitive to SSB price changes. Latent class analysis revealed five consumer groups, none of which fit the desirable policy-target of highly price sensitive, frequent SSB consumers. An improved understanding of responsiveness to beverage price changes and consumer preferences could improve predictions of whose health is likely to benefit most from pricing interventions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a paucity of evidence regarding the impact of sugar sweetened beverage (SSB) price increases on beverage consumption, using individual-level data, for the population overall and for different socioeconomic groups. This study aimed to predict the impact of altered beverage prices and educational messages on consumer purchasing behavior. 2020 adults representative of the Australian population by age, gender and income completed a discrete choice experiment online in 2016. Each subject completed 20 choice scenarios in a hypothetical convenience store setting where subjects chose between seven SSB and non-SSB beverage options or a no beverage option. Beverage prices and volumes varied between scenarios. Half of participants (n = 1012) were randomly exposed to an educational poster discouraging SSB consumption prior to completing choice scenarios. We used discrete choice models to predict purchases under several policy proposals, overall and for income and SSB consumption frequency sub-groups. Compared to baseline prices, a 10% SSB price increase was predicted to reduce SSB purchases by 15.0% [95%CI -15.2, -14.7], and increase purchases of non-SSBs by +11.0% [95%CI 10.8, 11.2] and no beverage by +15.5% [95%CI 15.1, 15.9]. Effects were greater with a 20% SSB price increase. Across all policy scenarios, the highest income quintile had a similar absolute and slightly greater relative decrease in SSB purchases compared to the lowest quintile. Educational poster exposure reduced SSB choice for all groups, with a greater reduction in the lower compared to higher income group, and additively increased response to price changes. Our results support the use of population-wide SSB pricing and educational interventions to reduce demand across all income groups., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Limited evidence has been gathered on the real-world impact of sugar-sweetened beverage price changes on purchasing behavior over time or in community-retail settings., Objective: Our aim was to determine changes in beverage purchases, business outcomes, and customer and retailer satisfaction associated with a retailer-led sugar-sweetened beverage price increase in a convenience store. We hypothesized that purchases of less-healthy beverages would decrease compared to predicted sales., Design: A convergent parallel mixed methods design complemented sales data (122 weeks pre-intervention, 17 weeks during intervention) with stakeholder interviews and customer surveys., Participants/setting: Electronic beverage sales data were collected from a convenience store in Melbourne, Australia (August through November 2015). Convenience store staff completed semi-structured interviews (n=4) and adult customers exiting the store completed surveys (n=352)., Intervention: Beverages were classified using a state government framework. Prices of "red" beverages (eg, nondiet soft drinks, energy drinks) increased by 20%. Prices of "amber" (eg, diet soft drinks, small pure fruit juices) and "green" beverages (eg, water) were unchanged., Main Outcome Measures: Changes in beverage volume, item sales, and revenue during the intervention were compared with predicted sales., Statistical Analyses: Sales data were analyzed using time series segmented regression while controlling for pre-intervention trends, autocorrelation in sales data, and seasonal fluctuations., Results: Beverage volume sales of red (-27.6%; 95% CI -32.2 to -23.0) and amber (-26.7%; 95% CI -39.3 to -16.0) decreased, and volume of green beverages increased (+26.9%; 95% CI +14.1 to +39.7) in the 17th intervention week compared with predicted sales. Store manager and staff considered the intervention business-neutral, despite a small reduction in beverage revenue. Fifteen percent of customers noticed the price difference and 61% supported the intervention., Conclusions: A 20% sugar-sweetened beverage price increase was associated with a reduction in their purchases and an increase in purchases of healthier alternatives. Community retail settings present a bottom-up approach to improving consumer beverage choices., (Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians' decision-making about this thrombolytic treatment. Methods A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians' views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase.