Dataset Information

Association between pediatric clinical trials and global burden of disease.

ABSTRACT:

Background

The allocation of research resources should favor conditions responsible for the greatest disease burden. This is particularly important in pediatric populations, which have been underrepresented in clinical research. Our aim was to measure the association between the focus of pediatric clinical trials and burden of disease and to identify neglected clinical domains.

Methods

We performed a cross-sectional study of clinical trials by using trial records in ClinicalTrials.gov. All trials started in 2006 or after and studying patient-level interventions in pediatric populations were included. Age-specific measures of disease burden were obtained for 21 separate conditions for high-, middle-, and low-income countries. We measured the correlation between number of pediatric clinical trials and disease burden for each condition.

Results

Neuropsychiatric conditions and infectious diseases were the most studied conditions globally in terms of number of trials (874 and 847 trials, respectively), while intentional injuries (5 trials) and maternal conditions (4 trials) were the least studied. Clinical trials were only moderately correlated with global disease burden (r = 0.58, P = .006). Correlations were also moderate within each of the country income levels, but lowest in low-income countries (r = .47, P = .03). Globally, the conditions most understudied relative to disease burden were injuries (-260 trials for unintentional injuries and -160 trials for intentional injuries), nutritional deficiencies (-175 trials), and respiratory infections (-171 trials).

Conclusions

Pediatric clinical trial activity is only moderately associated with pediatric burden of disease, and least associated in low-income countries. The mismatch between clinical trials and disease burden identifies key clinical areas for focus and investment.

SUBMITTER: Bourgeois FT

PROVIDER: S-EPMC3876184 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between pediatric clinical trials and global burden of disease.

Bourgeois Florence T FT Olson Karen L KL Ioannidis John P A JP Mandl Kenneth D KD

Pediatrics 20131216 1

<h4>Background</h4>The allocation of research resources should favor conditions responsible for the greatest disease burden. This is particularly important in pediatric populations, which have been underrepresented in clinical research. Our aim was to measure the association between the focus of pediatric clinical trials and burden of disease and to identify neglected clinical domains.<h4>Methods</h4>We performed a cross-sectional study of clinical trials by using trial records in ClinicalTrials ...[more]

PMID: 24344112

Similar Datasets

Project description:ObjectivesTo determine whether an association exists between the number of published randomised controlled trials and the global burden of disease, whether certain diseases are under-investigated relative to their burden, and whether the relation between the output of randomised trials and global burden of disease can be explained by the relative disease burden in high and low income regions.DesignCross sectional investigation.Study sampleAll primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013.Main outcome measuresNumber of trials conducted and number of participants randomised for each of 239 different diseases or injuries; variation in each outcome explainable by total disability adjusted life years (a measure of the overall burden of each disease) and the ratio of disability adjusted life years in low income to high income regions (a measure of whether a disease is more likely to affect people living in high income regions) quantified using multivariable regression.Results4190 abstracts were reviewed and 1351 primary randomised trials identified, of which 1097 could be classified using the global burden of disease taxonomy. Total disability adjusted life years was poorly associated with number of randomised trials and number of participants randomised in univariable analysis (Spearman's r=0.35 and 0.33, respectively), although it was a significant predictor in the univariable and multivariable models (P<0.001). Diseases for which the burden was predominantly located in low income regions had sevenfold fewer trials per million disability adjusted life years than diseases predominantly located in high income regions. However, only 26% of the variation in number of trials among diseases could be explained by total disability adjusted life years and the ratio of disability adjusted life years in low income regions to high income regions. Many high income type diseases (for example, neck pain, glomerulonephritis) have proportionally fewer randomised trials compared with low income type diseases (for example, vitamin A deficiency).ConclusionsOverall, a weak association existed between global burden of disease and number of published randomised trials. A global observatory for research is needed to monitor and reduce the discordance between the output of randomised trials and global burden of disease.

Project description:The course of Crohn's disease (CD) is heterogeneous, confounding effective personalized therapy. A previous analysis of differences in gene expression between patients with versus without CD groups revealed 2 subsets of patients with CD -- a group characterized by genes more highly expressed in the colon (colon-like CD) and a group with increased expression of ileum marker genes (ileum-like CD). We compared differences in microRNAs between these groups. We performed genome-wide microRNA profile analyses of colon tissues from 18 adults with CD and 12 adults without CD (controls). We performed principal component analyses to associate levels of microRNAs with CD subtypes. Colonic epithelial cells and lamina propria immune cells were isolated from intestinal tissues and levels of microRNA 31 (miR-31) were measured by real-time quantitative PCR. We validated the differential expression of miR-31 between the subtypes by measuring miR-31 levels in an independent cohort of 32 adult patients with CD and 23 controls. We generated epithelial colonoid cultures from controls and patients with CD, and measured levels of miR-31 in crypts. We performed genome-wide microRNA profile analyses of formalin-fixed paraffin-embedded colon and ileum biopsies from 76 treatment-naive pediatric patients with CD and 51 controls (234 samples) and collected data on disease features and outcomes. In comparing miRNA expression profiles between 9 patients with colon-like CD and 9 patients with ileum-like CD, we identified 19 miRNAs with significant differences in levels. We observed a 13.5-fold difference in level of miR-31-5p between tissues from patients with colon-like vs. ileum-like CD (Padj = 1.43 x 10-18). Principal component analysis found miR-31 to be the top contributor to the variance observed. Levels of miR-31 were increased 60-fold in tissues from patients with ileum-like CD compared with controls (Padj = 2.59 × 10-51). We validated the differential expression of miR-31 between the subtypes in the independent set of tissues. Colonoids derived from patients with CD had significantly higher levels of miR-31 than colonoids derived from control tissues (day 2 P=.041 and day 6 P=.0095). Levels of miR-31 were significantly increased in colon tissues from pediatric patients with CD compared with controls (~7.8-fold, P=4.64 ×10-7) and in ileum tissues from patients with CD patients vs. controls (~1.5-fold, P=9.97 × 10-7). A high level of miR-31 in index biopsies from pediatric patients with only inflammation and no other complications at time of diagnosis associated with development of fibrostenotic ileal CD. We identified differences in miR-31 levels in colon tissues from adult and pediatric patients with CD compared with controls, and in patients with ileum-like CD compared with colon-like CD. Further studies are needed to determine the mechanisms by which miR-31 might contribute to pathogenesis of this subtype of CD, or affect response to therapy.

Project description:BackgroundThis study examines the relationship between universal health coverage (UHC) and the burden of emergency diseases at a global level.MethodsData on Disability-Adjusted Life Years (DALYs) from emergency conditions were extracted from the Institute for Health Metrics and Evaluation (IHME) database for the years 2015 and 2019. Data on UHC, measured using two variables 1) coverage of essential health services and 2) proportion of the population spending more than 10% of household income on out-of-pocket health care expenditure, were extracted from the World Bank Database for years preceding our outcome of interest. A linear regression was used to analyze the association between UHC variables and DALYs for emergency diseases, controlling for other variables.ResultsA total of 132 countries were included. The median national coverage of essential health services index was 67.5/100, while the median national prevalence of catastrophic spending in the sample was 6.74% of households. There was a strong significant relationship between health service coverage and the burden of emergency diseases, with an 11.5-point reduction in DALYs of emergency medical diseases (95% CI -9.5, -14.8) for every point increase in the coverage of essential health services index. There was no statistically significant relationship between catastrophic expenditures and the burden of emergency diseases, which may be indicative of inelastic demand in seeking services for health emergencies.ConclusionIncreasing the coverage of essential health services, as measured by the essential health services index, is strongly correlated with a reduction in the burden of emergency conditions. In addition, data affirms that financial protection remains inadequate in many parts of the globe, with large numbers of households experiencing significant economic duress related to seeking healthcare. This evidence supports a strategy of strengthening UHC as a means of combating death and disability from health emergencies, as well as extending protection against impoverishment related to healthcare expenses.

Project description:The End TB Strategy places great emphasis on increasing social protection and poverty alleviation programmes. However, the role of social protection on controlling tuberculosis has not been examined fully. We analysed the association between social protection spending and tuberculosis prevalence, incidence, and mortality globally.We used publicly available data from WHO's Global Tuberculosis Programme for tuberculosis burden in terms of yearly incidence, prevalence, and mortality per 100,000 people, and social protection data from the International Labour Organization (ILO), expressed as the percentage of national gross domestic product (GDP) spent on social protection programmes (excluding health). Data from ILO were from 146 countries covering the years between 2000 and 2012. We used descriptive assessments to examine levels of social protection and tuberculosis burden for each country, then used these assessments to inform our fully adjusted multivariate regression models. Our models controlled for economic output, adult HIV prevalence, health expenditure, population density, the percentage of foreign-born residents, and the strength of the national tuberculosis treatment programme, and also incorporated a country-level fixed effect to adjust for clustering of datapoints within countries.Overall, social protection spending levels were inversely associated with tuberculosis prevalence, incidence, and mortality. For a country spending 0% of their GDP on social protection, moving to spending 1% of their GDP was associated with a change of -18·33 per 100,000 people (95% CI -32·10 to -4·60; p=0·009) in prevalence, -8·16 per 100,000 people (-16·00 to -0·27; p=0·043) in incidence, and -5·48 per 100,000 people (-9·34 to -1·62; p=0·006) in mortality. This association was mitigated at higher levels of social protection spending, and lost significance when more than 11% of GDP was spent.Our findings suggest that investments in social protection could contribute to a reduced tuberculosis burden, especially in countries that are investing a small proportion of their GDP in this area. However, further research is needed to support these ecological associations.National Institutes of Health National Center for Advancing Translational Science (University of California, Los Angeles [CA, USA] Clinical and Translational Science Institute).

Project description:ImportanceAlthough female representation has increased in clinical trials, little is known about how clinical trial representation compares with burden of disease or is associated with clinical trial features, including disease category.ObjectiveTo describe the rate of sex reporting (ie, the presence of clinical trial data according to sex), compare the female burden of disease with the female proportion of clinical trial enrollees, and investigate the associations of disease category and clinical trial features with the female proportion of clinical trial enrollees.Design, setting, and participantsThis cross-sectional study included descriptive analyses and logistic and generalized linear regression analyses with a logit link. Data were downloaded from the Aggregate Analysis of ClinicalTrials.gov database for all studies registered between March 1, 2000, and March 9, 2020. Enrollment was compared with data from the 2016 Global Burden of Disease database. Of 328 452 clinical trials, 70 095 were excluded because they had noninterventional designs, 167 936 because they had recruitment sites outside the US, 69 084 because they had no reported results, 1003 because they received primary funding from the US military, and 314 because they had unclear sex categories. A total of 20 020 interventional studies enrolling approximately 5.11 million participants met inclusion criteria and were divided into those with and without data on participant sex.ExposuresThe primary exposure variable was clinical trial disease category. Secondary exposure variables included funding, study design, and study phase.Main outcomes and measuresSex reporting and female proportion of participants in clinical trials.ResultsAmong 20 020 clinical trials from 2000 to 2020, 19 866 studies (99.2%) reported sex, and 154 studies (0.8%) did not. Clinical trials in the fields of oncology (46% of disability-adjusted life-years [DALYs]; 43% of participants), neurology (56% of DALYs; 53% of participants), immunology (49% of DALYs; 46% of participants), and nephrology (45% of DALYs; 42% of participants) had the lowest female representation relative to corresponding DALYs. Male participants were underrepresented in 8 disease categories, with the greatest disparity in clinical trials of musculoskeletal disease and trauma (11.3% difference between representation and proportion of DALYs). Clinical trials of preventive interventions were associated with greater female enrollment (adjusted relative difference, 8.48%; 95% CI, 3.77%-13.00%). Clinical trials in cardiology (adjusted relative difference, -18.68%; 95% CI, -22.87% to -14.47%) and pediatrics (adjusted relative difference, -20.47%; 95% CI, -25.77% to -15.16%) had the greatest negative association with female enrollment.Conclusions and relevanceIn this study, sex differences in clinical trials varied by clinical trial disease category, with male and female participants underrepresented in different medical fields. Although sex equity has progressed, these findings suggest that sex bias in clinical trials persists within medical fields, with negative consequences for the health of all individuals.

Dataset Information

Association between pediatric clinical trials and global burden of disease.

Background

Methods

Results

Conclusions

Publications

Association between pediatric clinical trials and global burden of disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets