The cost-effectiveness of preventive and treatment interventions for eating disorders

This PhD research evaluated economic benefit of preventive and treatment interventions for anorexia nervosa and bulimia nervosa within the Australian contex

Prevention of high body mass index and eating disorders : a systematic review and meta-analysis

Background: Eating disorders (EDs) and high body mass index (BMI) are two important public health issues with significant health and cost impacts. The aim of this systematic review and meta-analysis was to establish whether interventions are effective in preventing both issues. Methods: Electronic databases were searched up to 10 May 2021. Studies were included if they were randomised or quasi-randomised controlled trials that evaluated a preventive intervention (regardless of its aim to prevent ED, high BMI or both) and reported both EDs and BMI-related outcomes. Both narrative synthesis and meta-analysis were used to synthesise the results. Publication bias was also investigated. Results: Fifty-four studies were included for analysis. The primary aim of the studies was ED prevention (n = 23), high BMI prevention (n = 21) and both ED and high BMI prevention (n = 10). Meta-analysis results indicated that preventive interventions had a significant effect on several ED outcomes including dieting, shape and weight concerns, body dissatisfaction, negative affect, eating disorder symptoms and internalization, with effect sizes ranging from – 0.16 (95% CI – 0.27, – 0.06) to – 0.61 (95% CI – 0.29, – 0.04). Despite several studies that demonstrated positive impacts on BMI, there was no significant effect on BMI-related measures in the meta-analysis. The risk of publication bias was low for the majority of the pooled effect results. Conclusion: Preventive interventions were effective for either high BMI or EDs. However, there is limited evidence to show that current preventive interventions were effective in reducing both outcomes. Further research is necessary to explore the risk factors that are shared by these weight-related disorders as well as effective prevention interventions. Level of evidence: Level I: systematic review

Cost-effectiveness of anti-retroviral adherence interventions for people living with HIV: A systematic review of decision analytical models

Background: Although safe and effective anti-retrovirals (ARVs) are readily available, non-adherence to ARVs is highly prevalent among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (PLWHA). Different adherence-improving interventions have been developed and examined through decision analytic model-based health technology assessments. This systematic review aimed to review and appraise the decision analytical economic models developed to assess ARV adherence-improvement interventions. Methods: The review protocol was registered on PROSPERO (CRD42022270039), and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Relevant studies were identified through searches in six generic and specialized bibliographic databases, i.e. PubMed, Embase, NHS Economic Evaluation Database, PsycINFO, Health Economic Evaluations Database, tufts CEA registry and EconLit, from their inception to 23 October 2022. The cost-effectiveness of adherence interventions is represented by the incremental cost-effectiveness ratio (ICER). The quality of studies was assessed using the quality of the health economics studies (QHES) instrument. Data were narratively synthesized in the form of tables and texts. Due to the heterogeneity of the data, a permutation matrix was used for quantitative data synthesis rather than a meta-analysis. Results: Fifteen studies, mostly conducted in North America (8/15 studies), were included in the review. The time horizon ranged from a year to a lifetime. Ten out of 15 studies used a micro-simulation, 4/15 studies employed Markov and 1/15 employed a dynamic model. The most commonly used interventions reported include technology based (5/15), nurse involved (2/15), directly observed therapy (2/15), case manager involved (1/15) and others that involved multi-component interventions (5/15). In 1/15 studies, interventions gained higher quality-adjusted life years (QALYs) with cost savings. The interventions in 14/15 studies were more effective but at a higher cost, and the overall ICER was well below the acceptable threshold mentioned in each study, indicating the interventions could potentially be implemented after careful interpretation. The studies were graded as high quality (13/15) or fair quality (2/15), with some methodological inconsistencies reported. Conclusion: Counselling and smartphone-based interventions are cost-effective, and they have the potential to reduce the chronic adherence problem significantly. The quality of decision models can be improved by addressing inconsistencies in model selection, data inputs incorporated into models and uncertainty assessment methods

Cost–effectiveness analysis of pharmacist adherence interventions in people living with HIV/AIDS in Pakistan

Background: Evidence has shown the positive impact of pharmacist involvement on the adherence and health outcomes of people living with HIV/AIDS. However, whether such intervention provides value for money remains unclear. This study aims to fill this gap by assessing the cost–effectiveness of pharmacist interventions in HIV care in Pakistan. Methods: A Markov decision analytic model was constructed, considering clinical inputs, utility data, and cost data obtained from a randomized controlled trial and an HIV cohort of Pakistani origin. The analysis was conducted from a healthcare perspective, and the incremental cost–effectiveness ratio (ICER) was calculated and presented for the year 2023. Additionally, a series of sensitivity analyses were performed to assess the robustness of the results. Results: Pharmacist intervention resulted in higher quality-adjusted life years (4.05 vs. 2.93) and likewise higher annual intervention costs than usual care (1979 USD vs. 429 USD) (532,894 PKR vs. 115,518 PKR). This yielded the ICER of 1383 USD/quality-adjusted life years (QALY) (372,406 PKR/QALY), which is well below the willingness-to-pay threshold of 1658 USD (446,456 PKR/QALY) recommended by the World Health Organization Choosing Interventions that are Cost-Effective. Probabilistic sensitivity analysis reported that more than 68% of iterations were below the lower limit of threshold. Sensitivity analysis reported intervention cost is the most important parameter influencing the ICER the most. Conclusion: The study suggests that involving pharmacists in HIV care could be a cost-effective approach. These findings could help shape healthcare policies and plans, possibly making pharmacist interventions a regular part of care for people with HIV in Pakistan

Cost-effectiveness of installing barriers at bridge and cliff sites for suicide prevention in Australia

Importance: Installation of barriers has been shown to reduce suicides. To our knowledge, no studies have evaluated the cost-effectiveness of installing barriers at multiple bridge and cliff sites where suicides are known to occur. Objective: To examine the cost-effectiveness of installing barriers at bridge and cliff sites throughout Australia. Design, Setting, and Participants: This economic evaluation used an economic model to examine the costs, costs saved, and reductions in suicides if barriers were installed across identified bridge and cliff sites over 5 and 10 years. Specific and accessible bridge and cliff sites across Australia that reported 2 or more suicides over a 5-year period were identified for analysis. A partial societal perspective (including intervention costs and monetary value associated with preventing suicide deaths) was adopted in the development of the model. Interventions: Barriers installed at bridge and cliff sites. Main Outcomes and Measures: Primary outcome was return on investment (ROI) comparing cost savings with intervention costs. Secondary outcomes included incremental cost-effectiveness ratio (ICER), comprising the difference in costs between installation of barriers and no installation of barriers divided by the difference in reduction of suicide cases. Uncertainty and sensitivity analyses were undertaken to examine the association of changes in suicide rates with barrier installation, adjustments to the value of statistical life, and changes in maintenance costs of barriers. Results: A total of 7 bridges and 19 cliff sites were included in the model. If barriers were installed at bridge sites, an estimated US $145 million (95$90 to $160 million) could be saved in prevented suicides over 5 years, and US$270 million (95% UI, $176 to$298 million) over 10 years. The estimated ROI ratio for building barriers over 10 years at bridges was 2.4 (95% UI, 1.5 to 2.7); the results for cliff sites were not significant (ROI, 2.0; 95% UI, -1.1 to 3.8). The ICER indicated monetary savings due to averted suicides over the intervention cost for bridges, although evidence for similar savings was not significant for cliffs. Results were robust in all sensitivity analyses except when the value of statistical life-year over 5 or 10 years only was used. Conclusions and Relevance: In an economic analysis, barriers were a cost-effective suicide prevention intervention at bridge sites. Further research is required for cliff sites

Interventions to prevent alcohol use: systematic review of economic evaluations

Background Alcohol use is a leading risk factor for death and disability worldwide. Aims We conducted a systematic review on the cost-effectiveness evidence for interventions to prevent alcohol use across the lifespan. Method Electronic databases (EMBASE, Medline, PsycINFO, CINAHL and EconLit) were searched for full economic evaluations and return-on-investment studies of alcohol prevention interventions published up to May 2021. The methods and results of included studies were evaluated with narrative synthesis, and study quality was assessed by the Drummond ten-point checklist. Results A total of 69 studies met the inclusion criteria for a full economic evaluation or return-on-investment study. Most studies targeted adults or a combination of age groups, seven studies comprised children/adolescents and one involved older adults. Half of the studies found that alcohol prevention interventions are cost-saving (i.e. more effective and less costly than the comparator). This was especially true for universal prevention interventions designed to restrict exposure to alcohol through taxation or advertising bans; and selective/indicated prevention interventions, which involve screening with or without brief intervention for at-risk adults. School-based interventions combined with parent/carer interventions were cost-effective in preventing alcohol use among those aged under 18 years. No interventions were cost-effective for preventing alcohol use in older adults. Conclusions Alcohol prevention interventions show promising evidence of cost-effectiveness. Further economic analyses are needed to facilitate policy-making in low- and middle-income countries, and among child, adolescent and older adult populations

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill &amp; Melinda Gates Foundation

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic