Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations.

OBJECTIVES: To investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness, and reproducibility. STUDY DESIGN AND SETTING: We evaluated a random sample of health economic evaluations indexed in MEDLINE during 2019. We included articles written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years, and/or disability-adjusted life years. Reproducible research practices, openness, and transparency in each article were extracted in duplicate. We explored whether reproducible research practices were associated with self-report use of a guideline. RESULTS: We included 200 studies published in 147 journals. Almost half were published as open access articles (n = 93; 47%). Most studies (n = 150; 75%) were model-based economic evaluations. In 109 (55%) studies, authors self-reported use a guideline (e.g., for study conduct or reporting). Few studies (n = 31; 16%) reported working from a protocol. In 112 (56%) studies, authors reported the data needed to recreate the incremental cost-effectiveness ratio for the base case analysis. This percentage was higher in studies using a guideline than studies not using a guideline (72/109 [66%] with guideline vs. 40/91 [44%] without guideline; risk ratio 1.50, 95% confidence interval 1.15-1.97). Only 10 (5%) studies mentioned access to raw data and analytic code for reanalyses. CONCLUSION: Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations. This study provides baseline data to compare future progress in the field.

[Tumour necrosis factor (TNF) antagonist therapy for paediatric inflammatory bowel disease: A systematic review]. / Antagonistas del factor de necrosis tumoral (TNF) en la enfermedad inflamatoria intestinal pediátrica: Una revisión sistemática.

Inflammatory bowel disease includes two chronic inflammatory diseases, ulcerative colitis and Crohn's disease. The burden of disease is increasing worldwide. A few reviews evaluating the paediatric use of tumour necrosis factor (TNF) antagonists have been published, although these mostly include observational studies and do not consider economic evaluations. This systematic review evaluated the available evidence regarding the efficacy, safety, and cost-effectiveness of TNF antagonist therapy for paediatric inflammatory bowel disease. We searched PubMed/MEDLINE, Embase, and Cochrane Central (up to May 2022). Nine randomized clinical trials and four economic evaluations that examined any anti-TNF drugs (e.g., infliximab, adalimumab, golimumab, and certolizumab) against different alternatives were included. In studies evaluating the efficacy of anti-TNF drugs in Crohn's disease, most assessed the efficacy of maintenance regimen in patients who had previously responded to induction (response=28%-63%, and clinical remission=17%-83% depending on dose, drug, and follow-up). In ulcerative colitis, maintenance treatment with anti-TNF drugs reported clinical remission rates between 17% and 44%. Nine studies reported information on adverse events. No clinical trials comparing different anti-TNF drugs were found. The findings from this review suggest that maintenance treatment with anti-TNF drugs (such as infliximab and adalimumab) in paediatric inflammatory bowel disease is probably effective and safe. However, the economic evaluations reported contradictory results of the cost-effectiveness ratios. Protocol registry: Open Science Framework: https://osf.io/wjmvf.

Reproducible research practices, openness and transparency in health economic evaluations: study protocol for a cross-sectional comparative analysis.

INTRODUCTION: There has been a growing awareness of the need for rigorously and transparent reported health research, to ensure the reproducibility of studies by future researchers. Health economic evaluations, the comparative analysis of alternative interventions in terms of their costs and consequences, have been promoted as an important tool to inform decision-making. The objective of this study will be to investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness and reproducibility. METHODS AND ANALYSIS: This is the study protocol for a cross-sectional comparative analysis. We registered the study protocol within the Open Science Framework (osf.io/gzaxr). We will evaluate a random sample of 600 cost-effectiveness analysis publications, a specific form of health economic evaluations, indexed in MEDLINE during 2012 (n=200), 2019 (n=200) and 2022 (n=200). We will include published papers written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years and/or disability-adjusted life years. Screening and selection of articles will be conducted by at least two researchers. Reproducible research practices, openness and transparency in each article will be extracted using a standardised data extraction form by multiple researchers, with a 33% random sample (n=200) extracted in duplicate. Information on general, methodological and reproducibility items will be reported, stratified by year, citation of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement and journal. Risk ratios with 95% CIs will be calculated to represent changes in reporting between 2012-2019 and 2019-2022. ETHICS AND DISSEMINATION: Due to the nature of the proposed study, no ethical approval will be required. All data will be deposited in a cross-disciplinary public repository. It is anticipated the study findings could be relevant to a variety of audiences. Study findings will be disseminated at scientific conferences and published in peer-reviewed journals.

[Endorsement of guidelines for reporting economic evaluation studies by Spanish biomedical journals]. / Apoyo a las guías de publicación para estudios de evaluación económica por parte de las revistas biomédicas españolas.

OBJECTIVE: To examine the endorsement of reporting guidelines for economic evaluation studies, such as the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) statement, by Spanish biomedical journals. METHOD: Cross-sectional analysis of the instructions to authors of Spanish biomedical journals included in the Journal Citation Reports 2017. Two authors examined and extracted the following information: mention of any reporting guideline, the CHEERS statement, the recommendations of the International Committee of Medical Journal Directors (ICMJE) and the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network. RESULTS: Of the 28 journals included, 23 (82.1%; 95% confidence interval [95%CI]: 63.1-93.9%) mentioned at least one reporting guideline in the instructions to authors. Only one journal mentioned the CHEERS statement for health economic evaluations. Twenty-four journals (85.7%; 95%CI: 67.3-96.0%) mentioned the ICMJE recommendations and 8 (28.6%; 95%CI: 13.2-48.7%) mentioned the EQUATOR network. The CONSORT (Consolidated Standards of Reporting Trials) statement for clinical trials was the most- mentioned reporting guideline (n=21; 75.0%; 95%CI: 55.1-89.3%). DISCUSSION: Most of the instructions to authors do not provide guidance on how to report economic evaluations. Journals should support compliance with reporting guidelines by authors and peer-reviewers.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study.

Importance: The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. Objective: To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus. Evidence Review: Cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) were evaluated for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods. Levels and trends were analyzed over time, as well as by the Sociodemographic Index (SDI). Changes in incident cases were categorized by changes due to epidemiological vs demographic transition. Findings: In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016. The smallest increase was seen in high SDI countries. Globally, population aging contributed 17%; population growth, 12%; and changes in age-specific rates, -1% to this change. The most common incident cancer globally for men was prostate cancer (1.4 million cases). The leading cause of cancer deaths and DALYs was tracheal, bronchus, and lung cancer (1.2 million deaths and 25.4 million DALYs). For women, the most common incident cancer and the leading cause of cancer deaths and DALYs was breast cancer (1.7 million incident cases, 535 000 deaths, and 14.9 million DALYs). In 2016, cancer caused 213.2 million DALYs globally for both sexes combined. Between 2006 and 2016, the average annual age-standardized incidence rates for all cancers combined increased in 130 of 195 countries or territories, and the average annual age-standardized death rates decreased within that timeframe in 143 of 195 countries or territories. Conclusions and Relevance: Large disparities exist between countries in cancer incidence, deaths, and associated disability. Scaling up cancer prevention and ensuring universal access to cancer care are required for health equity and to fulfill the global commitments for noncommunicable disease and cancer control.

The Burden of Cardiovascular Diseases Among US States, 1990-2016.

Importance: Cardiovascular disease (CVD) is the leading cause of death in the United States, but regional variation within the United States is large. Comparable and consistent state-level measures of total CVD burden and risk factors have not been produced previously. Objective: To quantify and describe levels and trends of lost health due to CVD within the United States from 1990 to 2016 as well as risk factors driving these changes. Design, Setting, and Participants: Using the Global Burden of Disease methodology, cardiovascular disease mortality, nonfatal health outcomes, and associated risk factors were analyzed by age group, sex, and year from 1990 to 2016 for all residents in the United States using standardized approaches for data processing and statistical modeling. Burden of disease was estimated for 10 groupings of CVD, and comparative risk analysis was performed. Data were analyzed from August 2016 to July 2017. Exposures: Residing in the United States. Main Outcomes and Measures: Cardiovascular disease disability-adjusted life-years (DALYs). Results: Between 1990 and 2016, age-standardized CVD DALYs for all states decreased. Several states had large rises in their relative rank ordering for total CVD DALYs among states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana, Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and CVD burden increased for a small number of states in the most recent years. Cardiovascular disease DALYs remained twice as large among men compared with women. Ischemic heart disease was the leading cause of CVD DALYs in all states, but the second most common varied by state. Trends were driven by 12 groups of risk factors, with the largest attributable CVD burden due to dietary risk exposures followed by high systolic blood pressure, high body mass index, high total cholesterol level, high fasting plasma glucose level, tobacco smoking, and low levels of physical activity. Increases in risk-deleted CVD DALY rates between 2006 and 2016 in 16 states suggest additional unmeasured risks beyond these traditional factors. Conclusions and Relevance: Large disparities in total burden of CVD persist between US states despite marked improvements in CVD burden. Differences in CVD burden are largely attributable to modifiable risk exposures.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015.

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

[Potential sponsorship bias in cost-effectiveness analyses of healthcare interventions: A cross-sectional analysis]. / Potencial sesgo de patrocinio en los análisis coste-efectividad de intervenciones sanitarias: un análisis transversal.

OBJECTIVE: To examine the relationship between the funding source of cost-effectiveness analyses of healthcare interventions published in Spain and study conclusions. DESIGN: Descriptive cross-sectional study. LOCATION: Scientific literature databases (until December 2014). PARTICIPANTS (ANALYSIS UNITS): Cohort of cost-effectiveness analysis of healthcare interventions published in Spain between 1989-2014 (n=223) presenting quality-adjusted life years (QALYs) as the outcome measure. MAIN MEASUREMENTS: The relationship between qualitative conclusions of the studies and the type of funding source were established using Fisher's exact test in contingency tables. Distributions of the incremental cost-effectiveness ratios by source of funding in relation to hypothetical willingness to pay thresholds between €30,000-€50,000 per QALY were explored. RESULTS: A total of 136 (61.0%) studies were funded by industry. The industry-funded studies were less likely to report unfavorable or neutral conclusions than studies non-funded by industry (2.2% vs. 23.0%; P<.0001), largely driven by studies evaluating drugs (0.9% vs. 21.4%; P<.0001). The incremental cost-effectiveness ratios in studies funded by industry were more likely to be below the hypothetical willingness to pay threshold of €30,000 (73.8% vs. 56.3%; P<.0001) and €50,000 (89.4% vs. 68.2%; P<.0001) per QALY. CONCLUSIONS: This study reveals a potential sponsorship bias in cost-effectiveness analyses of healthcare interventions. Studies funded by industry could be favoring the efficiency profile of their products.

Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013: Findings From the Global Burden of Disease 2013 Study.

IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

The quality of reporting methods and results of cost-effectiveness analyses in Spain: a methodological systematic review.

BACKGROUND: Cost-effectiveness analysis has been recognized as an important tool to determine the efficiency of healthcare interventions and services. There is a need for evaluating the reporting of methods and results of cost-effectiveness analyses and establishing their validity. We describe and examine reporting characteristics of methods and results of cost-effectiveness analyses conducted in Spain during more than two decades. METHODS: A methodological systematic review was conducted with the information obtained through an updated literature review in PubMed and complementary databases (e.g. Scopus, ISI Web of Science, National Health Service Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases from Centre for Reviews and Dissemination (CRD), Índice Médico Español (IME) Índice Bibliográfico Español en Ciencias de la Salud (IBECS)). We identified cost-effectiveness analyses conducted in Spain that used quality-adjusted life years (QALYs) as outcome measures (period 1989-December 2014). Two reviewers independently extracted the data from each paper. The data were analysed descriptively. RESULTS: In total, 223 studies were included. Very few studies (10; 4.5 %) reported working from a protocol. Most studies (200; 89.7 %) were simulation models and included a median of 1000 patients. Only 105 (47.1 %) studies presented an adequate description of the characteristics of the target population. Most study interventions were categorized as therapeutic (189; 84.8 %) and nearly half (111; 49.8 %) considered an active alternative as the comparator. Effectiveness of data was derived from a single study in 87 (39.0 %) reports, and only few (40; 17.9 %) used evidence synthesis-based estimates. Few studies (42; 18.8 %) reported a full description of methods for QALY calculation. The majority of the studies (147; 65.9 %) reported that the study intervention produced "more costs and more QALYs" than the comparator. Most studies (200; 89.7 %) reported favourable conclusions. Main funding source was the private for-profit sector (135; 60.5 %). Conflicts of interest were not disclosed in 88 (39.5 %) studies. CONCLUSIONS: This methodological review reflects that reporting of several important aspects of methods and results are frequently missing in published cost-effectiveness analyses. Without full and transparent reporting of how studies were designed and conducted, it is difficult to assess the validity of study findings and conclusions.

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013.

BACKGROUND: The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. METHODS: Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. RESULTS: In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. CONCLUSIONS: Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.