Personal and societal costs of multiple sclerosis in the UK: A population-based MS Registry study.

OBJECTIVES: To investigate through survey and data linkage, healthcare resource use and costs (except drugs), including who bears the cost, of multiple sclerosis in the United Kingdom by disease severity and type. METHODS: The United Kingdom Multiple Sclerosis Register deployed a cost of illness survey, completed by people with multiple sclerosis and linked this with data within the United Kingdom Multiple Sclerosis Register and from their hospital records. Resource consumption was categorised as being medical or non-medical and costed by National Health Service and social services estimates for 2018. RESULTS: We calculated £509,003 in non-medical costs over a year and £435,488 in medical costs generated over 3 months. People with multiple sclerosis reported self-funding 75% of non-medical costs with non-medical interventions having long-term potential benefits. Costs increased with disability as measured by patient-reported Expanded Disability Status Score and Multiple Sclerosis Impact Scale, with Multiple Sclerosis Impact Scale physical being a more powerful predictor of costs than the patient-reported Expanded Disability Status Score. Two distinct groups were identified: medical and non-medical interventions (n = 138); and medical interventions only (n = 399). The medical and non-medical group reported increased disease severity and reduced employment but incurred 80% more medical costs per person than the medical-only group. CONCLUSIONS: The importance of disability in driving costs is illustrated with balance between medical and non-medical costs consistent with the United Kingdom health environment. People with multiple sclerosis and their families fund a considerable proportion of non-medical costs but non-medical interventions with longer term impact could affect future medical costs.

Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales.

BACKGROUND: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. METHODS: We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. RESULTS: Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be -178.8 g (95% CI -225.43 to -134.47 g) in the Danish population and -210.08 g (95% CI -281.97 to -141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. CONCLUSIONS: CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.

A case study of the Secure Anonymous Information Linkage (SAIL) Gateway: a privacy-protecting remote access system for health-related research and evaluation.

With the current expansion of data linkage research, the challenge is to find the balance between preserving the privacy of person-level data whilst making these data accessible for use to their full potential. We describe a privacy-protecting safe haven and secure remote access system, referred to as the Secure Anonymised Information Linkage (SAIL) Gateway. The Gateway provides data users with a familiar Windows interface and their usual toolsets to access approved anonymously-linked datasets for research and evaluation. We outline the principles and operating model of the Gateway, the features provided to users within the secure environment, and how we are approaching the challenges of making data safely accessible to increasing numbers of research users. The Gateway represents a powerful analytical environment and has been designed to be scalable and adaptable to meet the needs of the rapidly growing data linkage community.

Volunteer bias in recruitment, retention, and blood sample donation in a randomised controlled trial involving mothers and their children at six months and two years: a longitudinal analysis.

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children.