An evaluation of small-area statistical methods for detecting excess risk: with applications in breast and colon cancer mortality in Scotland 1986-1995

The need to report data at small-area level is constantly increasingly. In a society which is both health-conscious and environmentally aware, statistics at small-area level have a high degree of political significance. This type of data is required to plan and implement regional policies and apportion health care in accordance to the differing needs of the population. Recent advances in computer power has brought many advances to this area of study. For all the advances in technology and methodology, the problem of small numbers consistently appears. Is there an excess risk or is it down to chance? This is a question which is paramount in small-area statistics and will be addressed in this thesis. An overview of the thesis is provided below: Chapter 1 introduces the concept of small-area statistics and some of the social and political issues connected with this topic. There is a discussion of the analysis of small-area health data and the principal ideas that need to be considered in a statistical, political and social sense in this area of work. The aims of ISD Scotland are introduced and how they can be linked to this field of study. Chapter 2 describes an overview of the methods used in small-area statistics. The chapter begins by firstly considering the Standardised Incidence Ratio (SIR) which is the technique mainly used in the basic analysis done by ISD Scotland. Other techniques are then considered, however not all of these techniques are directly comparable to each other. The strengths and weaknesses of these techniques in previous research are discussed to give an idea of how the techniques perform in different scenarios. Chapter 3 is a simulation study of three of the techniques discussed in Chapter 2, these being the SIR, Circular Spatial Scan and Flexibly-Shaped Spatial Scan. The reason for this simulation study is to evaluate these techniques on simulated data arising from real scenarios. The strengths and weaknesses of these techniques are then highlighted which will prove helpful when analysing the data in Chapter 4. Chapter 4 provides an analysis of the mortality of breast and colon cancer in Scotland in the ten-year time period from 1986 to 1995. Using data provided by ISD Scotland, the analysis is carried out to identity any potential mortality clusters in both diseases. Chapter 5 provides a conclusion to this research by providing a summary of findings of the thesis and gives recommendations based upon these findings. A discussion is also given for potential further study in this field that could provide some value to ISD Scotland as they look to other ways of analysing their small-area data

Enhancing the understanding and application of burden of disease methods

Burden of disease studies can be used to summarise the combined impact that causes of morbidity and mortality have in a defined population in a manner that is consistent and comparable. They have become an increasingly popular means to use in knowledge exchange activities for informing national, and local, policy-making decisions. The Global Burden of Disease (GBD) study provide estimates on the burden of disease for each cause of disease and injury for individual countries, and sub-national areas for selected countries, which are adopted by many researchers and national public health institutes. Alternative national burden of disease studies exist, independent of the GBD study, which utilise country-specific data sources that are representative of the state of health in their country. The co-existence of these studies can potentially be problematic for knowledge exchange activities, particularly when estimates differ and neither party are able to explain why the differences exist. This can often lead to speculation on why the differences occur, and the monopolisation of burden of disease research by the GBD study can often be problematic in ensuring a balanced narrative emerges. Many users often just seek to appraise differences in the input data as they often lack the experience, or will, to understand methodological processes as they are often complex and exhaustive. However, these differences in methods could plausibly play a key contribution in explaining differences in results. Two such methodological choices are in relation to the choice of severity distribution in assessing the non-fatal burden of disease, and the choice of standard population that is used when estimating standardised rates. These issues are tackled in the first part of this thesis. The impact of these methodological choices were appraised using approaches from the Scottish Burden of Disease study, relative to those of the GBD study. The first aim of this thesis is to establish whether using standard GBD study severity distributions result in major differences, compared to using severity distributions that better reflect the epidemiological situation in Scotland using the example of individual cancer types. The second aim of this thesis is to determine whether using different standard populations to standardise rates leads to major differences in how causes of disease and injury are ranked using disability-adjusted life years (DALYs). The research presented in this thesis gives insights into how impactful seemingly slight methodological choices can result in major differences. The second subset of research questions relate to establishing methods for COVID-19 burden of disease assessment, and monitoring the burden of COVID-19 using DALYs. The aims of this work presented in this thesis were to: (i) Assess which European countries were likely to be most vulnerable to severe outcomes from COVID-19; (ii) Develop an international consensus method for estimating COVID-19 DALYs; (iii) Estimate COVID-19 DALYs in Scotland during 2020 and contextualise the result compared to the leading pre-pandemic causes of disease; (iv) Estimate the extent of inequality in COVID-19 DALYs in Scotland during 2020; (v) Provide an alternative way of assessing the impact of all-cause inequalities by comparing inequality-attributable DALYs to the impact of COVID-19; (vi) Monitor changes in the fatal COVID-19 burden of disease in 2021, in the context of vaccine availability, compared to 2020. The research questions posed in this thesis are investigated in the included seven firstauthor papers. The insights from each of the papers are synthesised in an explanatory essay. This essay attempts to show the impact of each of the individual papers, and how they form a cohesive body of work that enhances the understanding and application of methods for use in burden of disease assessment. The explanatory essay presents a two-tier approach. The first part considers the impact of: (i) severity distributions; and, (ii) standard populations in age-standardised rate calculations, in burden of disease assessment. The essay discusses the importance of the findings from the included papers. It also highlights their importance for other stakeholders in international burden of disease research networks’, given the impact of severity distributions on resulting estimates is now more widely understood. The second part of the explanatory essay focuses on developing consensus methods to estimate COVID-19 DALYs, and then focuses on their application in monitoring the overall, and inequalities in the, COVID-19 burden of disease in Scotland. The need for a consensus method is justified on the basis of ensuring that the comparative properties of DALYs remain. This work has synergies with the first part of the explanatory essay, as it is important that assessments are reflective of the best available country-specific data inputs. The significance of this work is discussed through its uptake within the international research community. The rationale for undertaking burden of disease assessments it to generate comparable estimates for where risk factors, causes of death, disease and injury are causing the largest public health losses. In doing this, it provides compelling evidence to inform resource allocation discussions for tackling population health needs, and the implications for which these needs will have in ensuring care services and workforces are proportionate to the challenge. Through presenting developments and the journey through these seven published works in included in this thesis, I aim to have demonstrated the importance of the work in enhancing the understanding and application of burden of disease assessment methods. It is vital that the methodological context, and any uncertainties for which estimates are produced in, is well understood

Life expectancy, healthy life expectancy, and inequalities in Hong Kong, 2007–2020

No abstract available

Measuring disability-adjusted life years (DALYs) due to low back pain in Malta

Background: Low back pain (LBP) is a public health concern and a leading cause of ill health. A high prevalence of musculoskeletal complaints has been reported for Malta, a small European state. The aim was to estimate for the first time the burden of LBP at population level in Malta in terms of disability-adjusted life years (DALYs) and compare to estimates obtained by the Global Burden of Disease (GBD) study. Method: The Maltese European Health Interview Survey dataset for 2015 provided the LBP prevalence data through representative self-reported history of chronic LBP within the past 12 months in combination with limitations to daily activities. Proportions of LBP severity (with and without leg pain – mild, moderate, severe and most severe) and their corresponding disability weights followed values reported in the GBD study. Years lived with disability (YLD) for LBP were estimated for the whole population by age and sex. Since LBP does not carry any mortality, YLD reflected DALYs. The estimated local DALYs per 100,000 were compared to the GBD 2017 study results for Malta for the same year. Results: LBP with activity limitation gave a point prevalence of 6.4% (95% Uncertainty Interval [UI] 5.7–7.2%) (5.6% males [95% UI 4.6–6.6%]; 7.3% females [95% UI 6.2–8.4%]), contributing to a total of 23,649 (95% UI 20,974–26,463) Maltese suffering from LBP. The LBP DALYs were of 716 (95% UI 558–896) per 100,000. Females experienced higher LBP burden (739 [95% UI 575–927] DALYs per 100,000) than males (693 [95% UI 541–867] DALYs per 100,000). Our DALY estimates were lower than those reported by the GBD 2017 study (i.e., 1829 [95% UI 1300–2466] per 100,000). Conclusions: LBP imposes a substantial burden on the Maltese population. Differences observed between national estimates and those of the GBD study suggest the integration of updated locally sourced data into the model and encouraging local contributors in order to improve the DALY estimates of each country. Keywords: Low back pain, Epidemiology, Burden, Outcome research, Malta, Burden of disease, YLL, YLD, DALYs, GBD, European burden of disease networkpeer-reviewe

Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017 : a systematic analysis for the global burden of disease study 2017

Background: Assessments of age-specifc mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Afairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specifc mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in diferent components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specifc mortality shows that there are remarkably complex patterns in population mortality across countries. The fndings of this study highlight global successes, such as the large decline in under-5 mortality, which refects signifcant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Socioeconomic inequalities in the non-fatal and fatal burden of disease: findings from Scottish Burden of Disease (SBoD) 2016 Scottish Burden of Disease Project Team

Background SBOD2015 was the first endeavour to produce burden of disease estimates in Scotland using linkage of routine health records. In 2017, the study highlighted disparities in burden due to morbidity and mortality with respect to age and gender for 132 conditions, diseases and injuries. Objectives The aim of SBOD2016 is to report on socioeconomic inequalities to provide further evidence to support preventable public health. Methods Morbidity estimates were estimated using an extensive range of administrative datasets to provide a transparent and systematic approach to describe non-fatal population health loss. Combining these estimates with the Global Burden of Disease 2016 study’s relative assessment of severity and disability for each condition, we were able to calculate the Years Lived with Disability (YLD). Death registrations were used alongside life expectancy data to calculate the Years of Life Lost to premature mortality (YLL) as a measure of fatal burden. Findings Preliminary findings show a three-fold increase in the burden of disease between individuals living in the most deprived areas compared to the least deprived areas. The profile of diseases contributing the largest burden also varies between the most and least deprived areas. Conclusions By combining information on fatal burden with the burden of living in less than ideal health (non-fatal burden), planners and policymakers have a better idea of the contribution that different diseases, conditions and injuries make to the total burden of disease and how this varies by levels of deprivation. This in turn provides information to support decisions about where prevention and service activity should be focused. It also provides a way of looking at the proportion of the burden that can be explained by a range of exposures in the population such as poverty or smoking

What causes the burden of stroke in Scotland? A comparative risk assessment approach linking the Scottish Health Survey to administrative health data

Background: The availability of robust evidence to inform effective public health decision making is becoming increasingly important, particularly in a time of competing health demands and limited resources. Comparative Risk Assessments (CRA) are useful in this regard as they quantify the contribution of modifiable exposures to the disease burden in a population. The aim of this study is to assess the contribution of a range of modifiable exposures to the burden of disease due to stroke, an important public health problem in Scotland. Methods: We used individual-level response data from eight waves (1995–2012) of the Scottish Health Survey linked to acute hospital discharge records from the Scottish Morbidity Record 01 (SMR01) and cause of death records from the death register. Stroke was defined using the International Classification of Disease (ICD) 9 codes 430–431, 433–4 and 436; and the ICD10 codes I60-61 and I63-64 and stroke incidence was defined as a composite of an individual’s first hospitalisation or death from stroke. A literature review identified exposures causally linked to stroke. Exposures were mapped to the layers of the Dahlgren & Whitehead model of the determinants of health and Population Attributable Fractions were calculated for each exposure deemed a significant causal risk of stroke from a Cox Proportional Hazards Regression model. Population Attributable Fractions were not summed as they may add to more than 100% due to the possibility of a person being exposed to more than one exposure simultaneously. Results: Overall, the results suggest that socioeconomic factors explain the largest proportion of incident stroke hospitalisations and deaths, after adjustment for confounding. After DAG adjustment, low education explained 38.8% (95% Confidence Interval 26.0% to 49.4%, area deprivation (as measured by the Scottish Index of Multiple Deprivation) 34.9% (95% CI 26.4 to 42.4%), occupational social class differences 30.3% (95% CI 19.4% to 39.8%), high systolic blood pressure 29.6% (95% CI 20.6% to 37.6%), smoking 25.6% (95% CI 17.9% to 32.6%) and area deprivation (as measured by the Carstairs area deprivation Index) 23.5% (95% CI 14.4% to 31.7%), of incident strokes in Scotland after adjustment. Conclusion: This study provides evidence for prioritising interventions that tackle socioeconomic inequalities as a means of achieving the greatest reduction in avoidable strokes in Scotland. Future work to disentangle the proportion of the effect of deprivation transmitted through intermediate mediators on the pathway between socioeconomic inequalities and stroke may offer additional opportunities to reduce the incidence of stroke in Scotland

Estimating the direct Covid-19 disability-adjusted life years impact on the Malta population for the first full year

Background: Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality, allowing for comprehensive comparisons of the population. The aim was to estimate the DALYs due to Covid-19 in Malta (March 2020–21) and investigate its impact in relation to other causes of disease at a population level. Methods: Mortality and weekly hospital admission data were used to calculate DALYs, based on the European Burden of Disease Network consensus Covid-19 model. Covid-19 infection duration of 14 days was considered. Sensitivity analyses for different morbidity scenarios, including post-acute consequences were presented. Results: An estimated 70,421 people were infected (with and without symptoms) by Covid-19 in Malta (March 2020–1), out of which 1636 required hospitalisation and 331 deaths, contributing to 5478 DALYs. These DALYs positioned Covid-19 as the fourth leading cause of disease in Malta. Mortality contributed to 95% of DALYs, while post-acute consequences contributed to 60% of morbidity. Conclusions: Covid-19 over 1 year has impacted substantially the population health in Malta. Post-acute consequences are the leading morbidity factors that require urgent targeted action to ensure timely multidisciplinary care. It is recommended that DALY estimations in 2021 and beyond are calculated to assess the impact of vaccine roll-out and emergence of new variants.peer-reviewe

How do world and European standard populations impact burden of disease studies? A case study of disability-adjusted life years (DALYs) in Scotland

Background Disability-Adjusted Life Years (DALYs) are an established method for quantifying population health needs and guiding prioritisation decisions. Global Burden of Disease (GBD) estimates aim to ensure comparability between countries and over time by using age-standardised rates (ASR) to account for differences in the age structure of different populations. Different standard populations are used for this purpose but it is not widely appreciated that the choice of standard may affect not only the resulting rates but also the rankings of causes of DALYs. We aimed to evaluate the impact of the choice of standard, using the example of Scotland. Methods DALY estimates were derived from the 2016 Scottish Burden of Disease (SBoD) study for an abridged list of 68 causes of disease/injury, representing a three-year annual average across 2014–16. Crude DALY rates were calculated using Scottish national population estimates. DALY ASRs standardised using the GBD World Standard Population (GBD WSP) were compared to those using the 2013 European Standard Population (ESP2013). Differences in ASR and in rank order within the cause list were summarised for all-cause and for each individual cause. Results The ranking of causes by DALYs were similar using crude rates or ASR (ESP2013). All-cause DALY rates using ASR (GBD WSP) were around 26% lower. Overall 58 out of 68 causes had a lower ASR using GBD WSP compared with ESP2013, with the largest falls occurring for leading causes of mortality observed in older ages. Gains in ASR were much smaller in absolute scale and largely affected causes that operated early in life. These differences were associated with a substantial change to the ranking of causes when GBD WSP was used compared with ESP2013. Conclusion Disease rankings based on DALY ASRs are strongly influenced by the choice of standard population. While GBD WSP offers international comparability, within-country analyses based on DALY ASRs should reflect local age structures. For European countries, including Scotland, ESP2013 may better guide local priority setting by avoiding large disparities occurring between crude and age-standardised results sets, which could potentially confuse non-technical audiences