A Guide to Handling Missing Data in Cost-Effectiveness Analysis Conducted Within Randomised Controlled Trials

The authors would like to thank Professor Adrian Grant and the team at the University of Aberdeen (Professor Craig Ramsay, Janice Cruden, Charles Boachie, Professor Marion Campbell and Seonaidh Cotton) who kindly allowed the REFLUX dataset to be used for this work, and Eldon Spackman for kindly sharing the Stata (R) code for calculating the probability that an intervention is cost effective following MI. The authors are grateful to the reviewers for their comments, which greatly improved this paper. M. G. is recipient of a Medical Research Council Early Career Fellowship in Economics of Health (grant number: MR/K02177X/1). I. R. W. was supported by the Medical Research Council [Unit Programme U105260558]. No specific funding was obtained to produce this paper. The authors declare no conflicts of interest.Missing data are a frequent problem in cost-effectiveness analysis (CEA) within a randomised controlled trial. Inappropriate methods to handle missing data can lead to misleading results and ultimately can affect the decision of whether an intervention is good value for money. This article provides practical guidance on how to handle missing data in within-trial CEAs following a principled approach: (i) the analysis should be based on a plausible assumption for the missing data mechanism, i.e. whether the probability that data are missing is independent of or dependent on the observed and/or unobserved values; (ii) the method chosen for the base-case should fit with the assumed mechanism; and (iii) sensitivity analysis should be conducted to explore to what extent the results change with the assumption made. This approach is implemented in three stages, which are described in detail: (1) descriptive analysis to inform the assumption on the missing data mechanism; (2) how to choose between alternative methods given their underlying assumptions; and (3) methods for sensitivity analysis. The case study illustrates how to apply this approach in practice, including software code. The article concludes with recommendations for practice and suggestions for future research.Medical Research Council Early Career Fellowship in Economics of Health MR/K02177X/1Medical Research Council UK (MRC) U105260558Medical Research Council UK (MRC) MC_U105260558 MR/K02177X/

Does Social Capital Promote Physical Activity? A Population-Based Study in Japan

To examine the association between individual-level social capital and physical activity.In February 2009, data were collected in a population-based cross-sectional survey in Okayama city, Japan. A cluster-sampling approach was used to randomly select 4,000 residents from 20 school districts. A total of 2260 questionnaires were returned (response rate: 57.4%). Individual-level social capital was assessed by an item inquiring about perceived trust of others in the community (cognitive dimension of social capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust (17.3%), as well as participation in voluntary groups (structural dimension of social capital), which further distinguished between bonding (8.9%) and bridging (27.1%) social capital. Using logistic regression, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with each domain of social capital. Multiple imputation method was employed for missing data. Among total participants, 68.8% were physically active and 28.9% were inactive. Higher trust was associated with a significantly lower odds of physical inactivity (OR = 0.58, 95% CI = 0.42-0.79) compared with low trust. Both bridging and bonding social capital were marginally significantly associated with lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62-1.00; bonding, OR = 0.71, 95% CI = 0.48-1.03) compared with lack of structural social capital.Low individual-level social capital, especially lower trust of others in the community, was associated with physical inactivity among Japanese adults

Colorectal Cancer Prognosis Following Obesity Surgery in a Population-Based Cohort Study

Background: Obesity surgery involves mechanical and physiological changes of the gastrointestinal tract that might promote colorectal cancer progression. Thus, we hypothesised that obesity surgery is associated with poorer prognosis in patients with colorectal cancer. Methods: This nationwide population-based cohort study included all patients with an obesity diagnosis who subsequently developed colorectal cancer in Sweden from 1980 to 2012. The exposure was obesity surgery, and the main and secondary outcomes were disease-specific mortality and all-cause mortality, respectively. Cox proportional hazard survival models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for sex, age, calendar year and education level. Results: The exposed and unexposed cohort included 131 obesity surgery and 1332 non-obesity surgery patients with colorectal cancer. There was a statistically significant increased rate of colorectal cancer deaths following obesity surgery (disease-specific HR 1.50, 95% CI 1.00–2.19). When analysed separately, the mortality rate was more than threefold increased in rectal cancer patients with prior obesity surgery (disease-specific HR 3.70, 95% CI 2.00–6.90), while no increased mortality rate was found in colon cancer patients (disease-specific HR 1.10, 85% CI 0.67–1.70). Conclusion: This population-based study among obese individuals found a poorer prognosis in colorectal cancer following obesity surgery, which was primarily driven by the higher mortality rate in rectal cancer

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

The ARIC predictive model reliably predicted risk of type II diabetes in Asian populations

10.1186/1471-2288-12-48BMC Medical Research Methodology12

Obesity, antenatal depression, diet and gestational weight gain in a population cohort study

Purpose: The aims of this paper are to examine: (1) the relationship between high pre-pregnancy BMI and antenatal depression; (2) whether BMI and antenatal depression interact to predict diet and gestational weight gain (GWG). Methods: Data came from the Avon Longitudinal Study of Parents and Children (ALSPAC). Underweight women were excluded. Pre-pregnancy BMI was self-reported and antenatal depression was assessed using the Edinburgh Postnatal Depression Scale at 18 and 32 weeks’ gestation to identify persistently elevated depressive symptoms (EPDS>12). Dietary patterns were calculated from food frequency questionnaires at 32 weeks’ gestation. GWG was categorised using the USA Institute of Medicine guidelines. Results: This study included 13,314 pregnant women. Obese women had significantly higher odds of antenatal depression than normal weight controls after adjusting for sociodemographics and health behaviours (aOR 1.39, 95%CI 1.05–1.84). Every unit increase in pre-pregnancy BMI was associated with approximately 3% higher odds of antenatal depression (aOR 1.03, 95%CI 1.01-1.05). Antenatal depression was not meaningfully associated with dietary patterns after adjusting for confounders and was not associated with inadequate or excessive GWG. There was no evidence for an interaction of depression and BMI on either diet or GWG. Conclusions Healthcare professionals should be aware of the dose-response relationship between high pre-pregnancy BMI and antenatal depression

A school-based intervention to reduce overweight and inactivity in children aged 6–12 years: study design of a randomized controlled trial

Background Effective interventions to prevent overweight and obesity in children are urgently needed especially in inner-city neighbourhoods where prevalence of overweight and inactivity among primary school children is high. A school based intervention was developed aiming at the reduction of overweight and inactivity in these children by addressing both behavioural and environmental determinants. Methods/design The main components of the intervention (Lekker Fit!) are the re-establishment of a professional physical education teacher; three (instead of two) PE classes per week; additional sport and play activities outside school hours; fitness testing; classroom education on healthy nutrition, active living and healthy lifestyle choices; and the involvement of parents. The effectiveness of the intervention is evaluated through a cluster randomized controlled trial in 20 primary schools among grades 3 through 8 (6–12 year olds). Primary outcome measures are BMI, waist circumference and fitness. Secondary outcome measures are assessed in a subgroup of grade 6–8 pupils (9–12 year olds) through classroom questionnaires and constitute of nutrition and physical activity behaviours and behavioural determinants. Multilevel regression analyses are used to study differences in outcomes between children in the intervention schools and in control schools, taking clustering of children within schools into account. Discussion Hypotheses are that the intervention results in a lower prevalence of children being overweight and an improved mean fitness score, in comparison with a control group where the intervention is not implemented. The results of our study will contribute to the discussion on the role of physical education and physical activity in the school curriculum. Trial registration [ISRCTN84383524

Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence

<p>Abstract</p> <p>Background</p> <p>Traditional prognostic factors in epithelial ovarian cancer (EOC) are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients.</p> <p>Methods</p> <p>MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome.</p> <p>Results</p> <p>MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p < 0.05). Moreover, multivariate analysis indicated that high expression levels of MGB-2 transcript (HR = 0.25, 95%, 0.08–0.75, p = 0.014) as well as positive immunostaining for the protein (HR = 0.41, 95%CI, 0.17–0.99, p = 0.048) had an independent prognostic value for disease-free survival.</p> <p>Conclusion</p> <p>This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can provide additional prognostic information about the risk of recurrence.</p

Determinants of Aortic Stiffness: 16-Year Follow-Up of the Whitehall II Study

Aortic stiffness is a strong predictor of cardiovascular disease endpoints. Cross-sectional studies have shown associations of various cardiovascular risk factors with aortic pulse wave velocity, a measure of aortic stiffness, but the long-term impact of these factors on aortic stiffness is unknown.In 3,769 men and women from the Whitehall II cohort, a wide range of traditional and novel cardiovascular risk factors were determined at baseline (1991-1993) and aortic pulse wave velocity was measured at follow-up (2007-2009). The prospective associations between each baseline risk factor and aortic pulse wave velocity at follow-up were assessed through sex stratified linear regression analysis adjusted for relevant confounders. Missing data on baseline determinants were imputed using the Multivariate Imputation by Chained Equations.Among men, the strongest predictors were waist circumference, waist-hip ratio, heart rate and interleukin 1 receptor antagonist, and among women, adiponectin, triglycerides, pulse pressure and waist-hip ratio. The impact of 10 centimeter increase in waist circumference on aortic pulse wave velocity was twice as large for men compared with women (men: 0.40 m/s (95%-CI: 0.24;0.56); women: 0.17 m/s (95%-CI: -0.01;0.35)), whereas the opposite was true for the impact of a two-fold increase in adiponectin (men: -0.30 m/s (95%-CI: -0.51;-0.10); women: 0.61 m/s (95%-CI: -0.86;-0.35)).In this large prospective study, central obesity was a strong predictor of aortic stiffness. Additionally, heart rate in men and adiponectin in women predicted aortic pulse wave velocity suggesting that strategies to prevent aortic stiffening should be focused differently by sex