Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Social inequality in diabetes patients' morbidity patterns from diagnosis to death - A Danish register-based investigation.

AIM: Measuring socioeconomic inequalities in health and health care, and understanding determinants of such inequalities, are critical for achieving higher equity in health. Equity in health is a prerequisite for public health and welfare. The aim of the paper is (1) to quantify inequality in diabetes morbidity patterns over patients' entire life span, and (2) to compare levels of inequality measured through income and educational level, respectively, as proxies for socioeconomic status (SES). METHOD: Historic individual register data on the entire Danish diabetes population alive in 2011 were gathered. Cox survival analysis and a concentration index decomposition approach were applied to analyse relevant morbidity indicators reflecting patients' health state at diagnosis and throughout their lives with diabetes. RESULTS: Patients with high education have approximately 26% lower mortality hazard when diagnosed with diabetes and 10-15% lower hazard of developing complications as compared with patients with short education. The outcome variables: 'severe complications at diagnosis' and 'years with severe complications' inhibit the highest negative concentration index value, indicating that morbidity is concentrated among the lower SES groups, whereas the outcome variables 'years without complications' and 'duration of diabetes' concentrate among the socioeconomically better-off patients. CONCLUSIONS: Significant differences in diabetes patients' morbidity patterns and survival indicate that diabetes impacts harder on patients of lower SES; these patients experience more severe complications and die earlier. Hence to reduce inequality in health, it is important to invest in efforts targeted towards socially vulnerable groups.

Socioeconomic inequality of diabetes patients' health care utilization in Denmark.

Understanding socioeconomic inequalities in health care is critical for achieving health equity. The aim of this paper is threefold: 1) to quantify inequality in diabetes health care service utilization; 2) to understand determinants of these inequalities in relation to socio-demographic and clinical morbidity factors; and 3) to compare the empirical outcome of using income level and educational level as proxies for Socio Economic Status (SES).Data on the entire Danish population of diabetes patients in 2011 (N = 318,729) were applied. Patients' unique personal identification number enabled individual patient data from several national registers to be linked. A concentration index approach with decomposition into contributing factors was applied. Differences in diabetes patients' health care utilization patterns suggest that use of services differ among patients of lower and higher SES, despite the Danish universal health care system. Especially, out-patient services, rehabilitation and specialists in primary care show different utilization patterns according to SES. Comparison of the empirical outcome from using educational level and income level as proxy for patients' SES indicate important differences in inequality estimates. While income, alike other measures of labor market attachment, to a certain extent is explained by morbidity and thus endogenous, education is more decisive for patients' ability to take advantage of the more specialized services provided in a universal health care system.