The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective: To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method: Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results: The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions: It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

Happy and healthy: a joint model of health and life satisfaction

Subjective well-being has been proposed as an alternative to preference based values of health benefit for use in economic evaluation. We develop a latent factor model of health and well-being in order to compare reported satisfaction with life, satisfaction with health and SF-6D responses. This approach provides a coherent, integrated statistical framework for assessing differences between these outcomes on the same scale. Using panel data from the British Household Panel Survey we find that SF-6D and satisfaction with health are influenced to a similar degree by changes in latent health and satisfaction with life is less responsive. For the average individual, there are no substantial differences in the relative impacts of physical versus mental health conditions between the three measures. These findings suggest that the differences between experienced and hypothetical values of health and life satisfaction may not lead to substantial differences in the assessment of value from health technologies

Happy and healthy: a joint model of health and life satisfaction

Subjective well-being has been proposed as an alternative to preference based values of health benefit for use in economic evaluation. We develop a latent factor model of health and well-being in order to compare reported satisfaction with life, satisfaction with health and SF-6D responses. This approach provides a coherent, integrated statistical framework for assessing differences between these outcomes on the same scale. Using panel data from the British Household Panel Survey we find that SF-6D and satisfaction with health are influenced to a similar degree by changes in latent health and satisfaction with life is less responsive. For the average individual, there are no substantial differences in the relative impacts of physical versus mental health conditions between the three measures. These findings suggest that the differences between experienced and hypothetical values of health and life satisfaction may not lead to substantial differences in the assessment of value from health technologies

Econometric modelling of multiple self-reports of health states: The switch from EQ-5D-3L to EQ-5D-5L in evaluating drug therapies for rheumatoid arthritis

EQ-5D is used in cost-effectiveness studies underlying many important health policy decisions. It comprises a survey instrument describing health states across five domains, and a system of utility values for each state. The original 3-level version of EQ-5D is being replaced with a more sensitive 5-level version but the consequences of this change are uncertain. We develop a multi-equation ordinal response model incorporating a copula specification with normal mixture marginals to analyse joint responses to EQ-5D-3L and EQ-5D-5L in a survey of people with rheumatic disease, and use it to generate mappings between the alternative descriptive systems. We revisit a major cost-effectiveness study of drug therapies for rheumatoid arthritis, mapping the original EQ-5D-3L measure onto a 5L valuation basis. Working within a comprehensive, flexible econometric framework, we find that use of simpler restricted specifications can make very large changes to cost-effectiveness estimates with serious implications for decision-making

The effects of breastfeeding on childhood BMI: a propensity score matching approach

BACKGROUND: Many studies have found a statistical association between breastfeeding and childhood adiposity. This paper investigates whether breastfeeding has an effect on subsequent childhood body mass index (BMI) using propensity scores to account for confounding. METHODS: We use data from the Millennium Cohort Study, a nationally representative UK cohort survey, which contains detailed information on infant feeding and childhood BMI. Propensity score matching is used to investigate the mean BMI in children breastfed exclusively and partially for different durations of time. RESULTS: We find statistically significant influences of breastfeeding on childhood BMI, particularly in older children, when breastfeeding is prolonged and exclusive. At 7 years, children who were exclusively breastfed for 16 weeks had a BMI 0.28 kg/m 2 (95% confidence interval 0.07 to 0.49) lower than those who were never breastfed, a 2% reduction from the mean BMI of 16.6 kg/m 2 . CONCLUSIONS: For this young cohort, even small effects of breastfeeding on BMI could be important. In order to reduce BMI, breastfeeding should be encouraged as part of wider lifestyle intervention. This evidence could help to inform public health bodies when creating public health guidelines and recommendations.This work was supported by the Economic and Social Research Council and the National Institute for Health and Care Excellence [grant number ES/H037977/1]

How is alcohol consumption and heavy episodic drinking spread across different types of drinking occasion in Great Britain: An event-level latent class analysis

Background This paper aimed to (i) update a previous typology of British alcohol drinking occasions using a more recent and expanded dataset and revised modelling procedure, and (ii) estimate the average consumption level, prevalence of heavy drinking, and distribution of all alcohol consumption and heavy drinking within and across occasion types. Methods The paper uses a cross-sectional latent class analysis of event-level diary data that includes characteristics of 43,089 drinking occasions in 2019 reported by 17,821 adult drinkers in Great Britain. The latent class indicators are characteristics of off-trade only (e.g. home), on-trade only (e.g. bar) and mixed trade (e.g. home and bar) drinking occasions. These describe companions, locations, purpose, motivation, accompanying activities, timings, consumption volume in units (1 UK unit = 8g ethanol) and beverages consumed. Results The analysis identified four off-trade only, eight on-trade only and three mixed-trade occasion types (i.e. latent classes). Mean consumption per occasion varied between 4.4 units in Family meals to 17.7 units in Big nights out with pre-loading. It exceeded ten units in all mixed-trade occasion types and in Off-trade get togethers, Big nights out and Male friends at the pub. Three off-trade types accounted for 50.8% of all alcohol consumed and 51.8% of heavy drinking occasions: Quiet drink at home alone, Evening at home with partner and Off-trade get togethers. For thirteen out of fifteen occasion types, more than 25% of occasions involved heavy drinking. Conversely, 41.7% of Big nights out and 16.4% of Big nights out with preloading were not heavy drinking occasions. Conclusions Alcohol consumption varies substantially across and within fifteen types of drinking occasion in Great Britain. Heavy drinking is common in most occasion types. However, moderate drinking is also common in occasion types often characterised as heavy drinking practices. Mixed-trade drinking occasions are particularly likely to involve heavy drinking

Children's development and parental input: Evidence from the UK Millennium Cohort Study

In this study, we use the UK Millennium Cohort Study to estimate a dynamic factor model of child development. Our model follows the children from birth until 7 years of age and allows for both cognitive and noncognitive abilities in children. We find a significant self-productivity effect in both cognitive and noncognitive development, as well as some evidence of dynamic dependence across different abilities. The activities that parents carry out with children at home (parental investment) have a significant effect on children’s development; we find substantial evidence of two distinct latent parental investment variables with differential effects across the two abilities

Predicting Productivity Losses from Health-Related Quality of Life Using Patient Data.

OBJECTIVE: This paper estimates productivity loss using the health of the patient in order to allow indirect estimation of these costs for inclusion in economic evaluation. METHODS: Data from two surveys of inpatients [Health outcomes data repository (HODaR) sample (n = 42,442) and health improvement and patient outcomes (HIPO) sample (n = 6046)] were used. The number of days off paid employment or normal activities (excluding paid employment) was modelled using the health of the patients measured by the EQ-5D, international classification of diseases (ICD) chapters, and other health and sociodemographic data. Two-part models (TPMs) and zero-inflated negative binomial (ZINB) models were identified as the most appropriate specifications, given large spikes at the minimum and maximum days for the dependent variable. Analysis was undertaken separately for the two datasets to account for differences in recall period and identification of those who were employed. RESULTS: Models were able to reflect the large spike at the minimum (zero days) but not the maximum, with TPMs doing slightly better than the ZINB model. The EQ-5D was negatively associated with days off employment and normal activities in both datasets, but ICD chapters only had statistically significant coefficients for some chapters in the HODaR. CONCLUSIONS: TPMs can be used to predict productivity loss associated with the health of the patient to inform economic evaluation. Limitations include recall and response bias and identification of who is employed in the HODaR, while the HIPO suffers from a small sample size. Both samples exclude some patient groups

An intervention to support adherence to inhaled medication in adults with cystic fibrosis: the ACtiF research programme including RCT

Background People with cystic fibrosis frequently have low levels of adherence to inhaled medications. Objectives The objectives were to develop and evaluate an intervention for adults with cystic fibrosis to improve adherence to their inhaled medication. Design We used agile software methods to develop an online platform. We used mixed methods to develop a behaviour change intervention for delivery by an interventionist. These were integrated to become the CFHealthHub intervention. We undertook a feasibility study consisting of a pilot randomised controlled trial and process evaluation in two cystic fibrosis centres. We evaluated the intervention using an open-label, parallel-group randomised controlled trial with usual care as the control. Participants were randomised in a 1 : 1 ratio to intervention or usual care. Usual care consisted of clinic visits every 3 months. We undertook a process evaluation alongside the randomised controlled trial, including a fidelity study, a qualitative interview study and a mediation analysis. We undertook a health economic analysis using both a within-trial and model-based analysis. Setting The randomised controlled trial took place in 19 UK cystic fibrosis centres. Participants Participants were people aged ≥ 16 years with cystic fibrosis, on the cystic fibrosis registry, not post lung transplant or on the active transplant list, who were able to consent and not using dry-powder inhalers. Intervention People with cystic fibrosis used a nebuliser with electronic monitoring capabilities. This transferred data automatically to a digital platform. People with cystic fibrosis and clinicians could monitor adherence using these data, including through a mobile application (app). CFHealthHub displayed graphs of adherence data as well as educational and problem-solving information. A trained interventionist helped people with cystic fibrosis to address their adherence. Main outcome measures Randomised controlled trial – adjusted incidence rate ratio of pulmonary exacerbations meeting the modified Fuchs criteria over a 12-month follow-up period (primary outcome); change in percentage adherence; and per cent predicted forced expiratory volume in 1 second (key secondary outcomes). Process evaluation – percentage fidelity to intervention delivery, and participant and interventionist perceptions of the intervention. Economic modelling – incremental cost per quality-adjusted life-year gained. Results Randomised controlled trial – 608 participants were randomised to the intervention (n = 305) or usual care (n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels. Limitations Number of exacerbations is a sensitive and valid measure of clinical change used in many trials. However, data collection of this outcome in this context was challenging and could have been subject to bias. It was not possible to measure baseline adherence accurately. It was not possible to quantify the impact of the intervention on the number of packs of medicines prescribed. Conclusions We developed a feasible and acceptable intervention that was delivered to fidelity in the randomised controlled trial. We observed no statistically significant difference in the primary outcome of exacerbation rates over 12 months. We observed an increase in normative adherence levels in a disease where adherence levels are low. The magnitude of the increase in adherence may not have been large enough to affect exacerbations

Growth dynamics : an empirical investigation of output growth using international data

The rates of growth of output per head vary across countries. Despite the fact that these differences are of a small order of magnitude, they would translate into large differences in the average living standards of the countries if they were to persist over the years. It is therefore very important to understand the process of long run growth and as a consequence many recent studies concentrate on the issue of cross country convergence.;The aim of this thesis is to investigate the process of growth across countries and the possibility of inter-relationships of these processes across countries. To this avail, an empirical analysis of per capita output across countries out first using the exact continuous time version of two neoclassical growth models, the Solow growth model and The Ramsey-Cass-Koopmans model. Results show that when these models are estimated consistently countries do not seem to be converging in the sense typically used in the literature. The rest of the thesis aims to investigate in more detail the processes by which growth in different countries might be related. Based on extensions of another neoclassical model, the Overlapping Generations model, and using a nonlinear switching regime model for estimation, two empirical analyses are carried out. The first one examines the role of balance of payments constraints in cross country growth determination. The second studies the extent of technology spillovers across countries and their effect on the process of growth. On one hand, results reveal little evidence of current account deficits constraining growth in the long run in the G7 countries although there is ample evidence of an influence in the short run dynamics of growth. On the other hand, spillovers of technology across the G7 countries are found to be of importance in the process of growth