DataSHIELD: resolving a conflict in contemporary bioscience--performing a pooled analysis of individual-level data without sharing the data.

BACKGROUND: Contemporary bioscience sometimes demands vast sample sizes and there is often then no choice but to synthesize data across several studies and to undertake an appropriate pooled analysis. This same need is also faced in health-services and socio-economic research. When a pooled analysis is required, analytic efficiency and flexibility are often best served by combining the individual-level data from all sources and analysing them as a single large data set. But ethico-legal constraints, including the wording of consent forms and privacy legislation, often prohibit or discourage the sharing of individual-level data, particularly across national or other jurisdictional boundaries. This leads to a fundamental conflict in competing public goods: individual-level analysis is desirable from a scientific perspective, but is prevented by ethico-legal considerations that are entirely valid. METHODS: Data aggregation through anonymous summary-statistics from harmonized individual-level databases (DataSHIELD), provides a simple approach to analysing pooled data that circumvents this conflict. This is achieved via parallelized analysis and modern distributed computing and, in one key setting, takes advantage of the properties of the updating algorithm for generalized linear models (GLMs). RESULTS: The conceptual use of DataSHIELD is illustrated in two different settings. CONCLUSIONS: As the study of the aetiological architecture of chronic diseases advances to encompass more complex causal pathways-e.g. to include the joint effects of genes, lifestyle and environment-sample size requirements will increase further and the analysis of pooled individual-level data will become ever more important. An aim of this conceptual article is to encourage others to address the challenges and opportunities that DataSHIELD presents, and to explore potential extensions, for example to its use when different data sources hold different data on the same individuals.

Income inequality and mortality: a multilevel prospective study of 521 248 individuals in 50 US states.

BACKGROUND: Some of the most consistent evidence in favour of an association between income inequality and health has been among US states. However, in multilevel studies of mortality, only two out of five studies have reported a positive relationship with income inequality after adjustment for the compositional characteristics of the state's inhabitants. In this study, we attempt to clarify these mixed results by analysing the relationship within age-sex groups and by applying a previously unused analytical method to a database that contains more deaths than any multilevel study to date. METHODS: The US National Longitudinal Mortality Study (NLMS) was used to model the relationship between income inequality in US states and mortality using both a novel and previously used methodologies that fall into the general framework of multilevel regression. We adjust age-sex specific models for nine socioeconomic and demographic variables at the individual level and percentage black and region at the state level. RESULTS: The preponderance of evidence from this study suggests that 1990 state-level income inequality is associated with a 40% differential in state level mortality rates (95% CI = 26-56%) for men 25-64 years and a 14% (95% CI = 3-27%) differential for women 25-64 years after adjustment for compositional factors. No such relationship was found for men or women over 65. CONCLUSIONS: The relationship between income inequality and mortality is only robust to adjustment for compositional factors in men and women under 65. This explains why income inequality is not a major driver of mortality trends in the United States because most deaths occur at ages 65 and over. This analysis does suggest, however, the certain causes of death that occur primarily in the population under 65 may be associated with income inequality. Comparison of analytical techniques also suggests coefficients for income inequality in previous multilevel mortality studies may be biased, but further research is needed to provide a definitive answer.