Dataset Information

Association between randomised trial evidence and global burden of disease: cross sectional study (Epidemiological Study of Randomized Trials--ESORT).

ABSTRACT:

Objectives

To 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.

Design

Cross sectional investigation.

Study sample

All primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013.

Main outcome measures

Number 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.

Results

4190 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).

Conclusions

Overall, 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.

SUBMITTER: Emdin CA

PROVIDER: S-EPMC4309646 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundNumerous population-based studies have documented high prevalence of scabies in overcrowded settings, particularly among children and in tropical regions. We provide an estimate of the global burden of scabies using data from the Global Burden of Disease (GBD) Study 2015.MethodsWe identified scabies epidemiological data sources from an extensive literature search and hospital insurance data and analysed data sources with a Bayesian meta-regression modelling tool, DisMod-MR 2·1, to yield prevalence estimates. We combined prevalence estimates with a disability weight, measuring disfigurement, itch, and pain caused by scabies, to produce years lived with disability (YLDs). With an assumed zero mortality from scabies, YLDs were equivalent to disability-adjusted life-years (DALYs). We estimated DALYs for 195 countries divided into 21 world regions, in both sexes and 20 age groups, between 1990 and 2015.FindingsScabies was responsible for 0·21% of DALYs from all conditions studied by GBD 2015 worldwide. The world regions of east Asia (age-standardised DALYs 136·32), southeast Asia (134·57), Oceania (120·34), tropical Latin America (99·94), and south Asia (69·41) had the greatest burden of DALYs from scabies. Mean percent change of DALY rate from 1990 to 2015 was less than 8% in all world regions, except North America, which had a 23·9% increase. The five individual countries with greatest scabies burden were Indonesia (age-standardised DALYs 153·86), China (138·25), Timor-Leste (136·67), Vanuatu (131·59), and Fiji (130·91). The largest standard deviations of age-standardised DALYs between the 20 age groups were observed in southeast Asia (60·1), Oceania (58·3), and east Asia (56·5), with the greatest DALY burdens in children, adolescents, and the elderly.InterpretationThe burden of scabies is greater in tropical regions, especially in children, adolescents, and elderly people. As a worldwide epidemiological assessment, GBD 2015 provides broad and frequently updated measures of scabies burden in terms of skin effects. These global data might help guide research protocols and prioritisation efforts and focus scabies treatment and control measures.FundingBill & Melinda Gates Foundation.

Project description:ObjectivesTo re-assess the quality of the epidemiological studies used to estimate the global burden of depression 2000, as published in the GBDep study.DesignPrimary and secondary data sources used in the global burden of depression estimate were identified and assigned to country of origin. Each source was assessed with respect to completeness and representativeness for national/regional estimates and against the inclusion criteria used by the scientific team estimating GBDep.SettingNot applicable.ParticipantsNot applicable.Main outcome measuresNot applicable.ResultsFirst, National estimates: The 28 scientific sources cited in the GBDep study related to 40 of the 191 WHO member countries. The EURO region had studies relating to 15 of 52 countries whereas AFRO region had studies for only three of 46 countries. Only six of the 40 countries had data drawn from a nationally representative population: the three AFRO country studies were based on a single village or town and, likewise, SEARO region had no nationally representative data; second, GBDep criteria: GBDep inclusion criteria required study sample size of more than 1000 people; 19 (45%) of the 42 studies did not meet this criterion. Sixteen (44%) of 36 studies did not meet the requirement that studies show a clear sample frame and method. GBD estimates rely on estimates of incidence; only two of the 42 country studies provided incidence data (Canada and Norway), the remaining 34 studies were prevalence studies. Duration of depression is based on three studies conducted in the USA and Holland.ConclusionsMost studies exhibit significant shortcomings and limitations with respect to study design and analysis and compliance with GBDep inclusion criteria. Poor quality data limit the interpretation and validity of global burden of depression estimates. The uncritical application of these estimates to international healthcare policy-making could divert scarce resources from other public healthcare priorities.

Project description:ObjectiveTo synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials.DesignSystematic review of meta-epidemiological studies.MethodsWe retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic.ResultsWe included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear.ConclusionsCertain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed.

Project description:BACKGROUND:Randomised controlled trials (RCTs) provide the most reliable information to inform clinical practice and patient care. We aimed to map global clinical research publication activity through RCT-related articles in high-impact-factor medical journals over the past five decades. METHODS:We conducted a cross-sectional analysis of articles published in the highest ranked medical journals with an impact factor > 10 (according to Journal Citation Reports published in 2017). We searched PubMed/MEDLINE (from inception to December 31, 2017) for all RCT-related articles (e.g. primary RCTs, secondary analyses and methodology papers) published in high-impact-factor medical journals. For each included article, raw metadata were abstracted from the Web of Science. A process of standardization was conducted to unify the different terms and grammatical variants and to remove typographical, transcription and/or indexing errors. Descriptive analyses were conducted (including the number of articles, citations, most prolific authors, countries, journals, funding sources and keywords). Network analyses of collaborations between countries and co-words are presented. RESULTS:We included 39,305 articles (for the period 1965-2017) published in forty journals. The Lancet (n = 3593; 9.1%), the Journal of Clinical Oncology (n = 3343; 8.5%) and The New England Journal of Medicine (n = 3275 articles; 8.3%) published the largest number of RCTs. A total of 154 countries were involved in the production of articles. The global productivity ranking was led by the United States (n = 18,393 articles), followed by the United Kingdom (n = 8028 articles), Canada (n = 4548 articles) and Germany (n = 4415 articles). Seventeen authors who had published 100 or more articles were identified; the most prolific authors were affiliated with Duke University (United States), Harvard University (United States) and McMaster University (Canada). The main funding institutions were the National Institutes of Health (United States), Hoffmann-La Roche (Switzerland), Pfizer (United States), Merck Sharp & Dohme (United States) and Novartis (Switzerland). The 100 most cited RCTs were published in nine journals, led by The New England Journal of Medicine (n = 78 articles), The Lancet (n = 9 articles) and JAMA (n = 7 articles). These landmark contributions focused on novel methodological approaches (e.g. the "Bland-Altman method") and trials on the management of chronic conditions (e.g. diabetes control, hormone replacement therapy in postmenopausal women, multiple therapies for diverse cancers, cardiovascular therapies such as lipid-lowering statins, antihypertensive medications, and antiplatelet and antithrombotic therapy). CONCLUSIONS:Our analysis identified authors, countries, funding institutions, landmark contributions and high-impact-factor medical journals publishing RCTs. Over the last 50 years, publication production in leading medical journals has increased, with Western countries leading in research but with low- and middle-income countries showing very limited representation.

Project description:ObjectivesTo assess the value of pilot and feasibility studies to randomised controlled trials (RCTs) funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. To explore the methodological components of pilot/feasibility studies and how they inform full RCTs.Study designCross-sectional study.SettingBoth groups included NIHR HTA programme funded studies in the period 1 January 2010-31 December 2014 (decision date). Group 1: stand-alone pilot/feasibility studies published in the HTA Journal or accepted for publication. Group 2: all funded RCT applications funded by the HTA programme, including reference to an internal and/or external pilot/feasibility study. The methodological components were assessed using an adapted framework from a previous study.Main outcome measuresThe proportion of stand-alone pilot and feasibility studies which recommended proceeding to full trial and what study elements were assessed. The proportion of 'HTA funded' trials which used internal and external pilot and feasibility studies to inform the design of the trial.ResultsGroup 1 identified 15 stand-alone pilot/feasibility studies. Study elements most commonly assessed were testing recruitment (100% in both groups), feasibility (83%, 100%) and suggestions for further study/investigation (83%, 100%). Group 2 identified 161 'HTA funded' applications: 59 cited an external pilot/feasibility study where testing recruitment (50%, 73%) and feasibility (42%, 73%) were the most commonly reported study elements: 92 reported an internal pilot/feasibility study where testing recruitment (93%, 100%) and feasibility (44%, 92%) were the most common study elements reported.Conclusions'HTA funded' research which includes pilot and feasibility studies assesses a variety of study elements. Pilot and feasibility studies serve an important role when determining the most appropriate trial design. However, how they are reported and in what context requires caution when interpreting the findings and delivering a definitive trial.

Project description:ObjectiveTo evaluate the agreement between diet-disease effect estimates of bodies of evidence from randomised controlled trials and those from cohort studies in nutrition research, and to investigate potential factors for disagreement.DesignMeta-epidemiological study.Data sourcesCochrane Database of Systematic Reviews, and Medline.Review methodsPopulation, intervention or exposure, comparator, outcome (PI/ECO) elements from a body of evidence from cohort studies (BoE(CS)) were matched with corresponding elements of a body of evidence from randomised controlled trials (BoE(RCT)). Pooled ratio of risk ratios or difference of mean differences across all diet-disease outcome pairs were calculated. Subgroup analyses were conducted to explore factors for disagreement. Heterogeneity was assessed through I2 and τ2. Prediction intervals were calculated to assess the range of possible values for the difference in the results between evidence from randomised controlled trials and evidence from cohort studies in future comparisons.Results97 diet-disease outcome pairs (that is, matched BoE(RCT) and BoE(CS)) were identified overall. For binary outcomes, the pooled ratio of risk ratios comparing estimates from BoE(RCT) with BoE(CS) was 1.09 (95% confidence interval 1.04 to 1.14; I2=68%; τ2=0.021; 95% prediction interval 0.81 to 1.46). The prediction interval indicated that the difference could be much more substantial, in either direction. We further explored heterogeneity and found that PI/ECO dissimilarities, especially for the comparisons of dietary supplements in randomised controlled trials and nutrient status in cohort studies, explained most of the differences. When the type of intake or exposure between both types of evidence was identical, the estimates were similar. For continuous outcomes, small differences were observed between randomised controlled trials and cohort studies.ConclusionOn average, the difference in pooled results between estimates from BoE(RCT) and BoE(CS) was small. But wide prediction intervals and some substantial statistical heterogeneity in cohort studies indicate that important differences or potential bias in individual comparisons or studies cannot be excluded. Observed differences were mainly driven by dissimilarities in population, intervention or exposure, comparator, and outcome. These findings could help researchers further understand the integration of such evidence into prospective nutrition evidence syntheses and improve evidence based dietary guidelines.

Project description:BACKGROUND:Cluster randomised trials with unequal sized clusters often have lower precision than with clusters of equal size. To allow for this, sample sizes are inflated by a modified version of the design effect for clustering. These inflation factors are valid under the assumption that randomisation is stratified by cluster size. We investigate the impact of unequal cluster size when that constraint is relaxed, with particular focus on the stepped-wedge cluster randomised trial, where this is more difficult to achieve. METHODS:Assuming a multi-level mixed effect model with exchangeable correlation structure for a cross-sectional design, we use simulation methods to compare the precision for a trial with clusters of unequal size to a trial with clusters of equal size (relative efficiency). For a range of scenarios we illustrate the impact of various design features (the cluster-mean correlation - a function of the intracluster correlation and the cluster size, the number of clusters, number of randomisation sequences) on the average and distribution of the relative efficiency. RESULTS:Simulations confirm that the average reduction in precision, due to varying cluster sizes, is smaller in a stepped-wedge trial compared to the parallel trial. However, the variance of the distribution of the relative efficiency is large; and is larger under the stepped-wedge design compared to the parallel design. This can result in large variations in actual power, depending on the allocation of clusters to sequences. Designs with larger variations in cluster sizes, smaller number of clusters and studies with smaller cluster-mean correlations (smaller cluster sizes or smaller intra-cluster correlation) are particularly at risk. CONCLUSION:The actual realised power in a stepped-wedge trial might be substantially higher or lower than that estimated. This is particularly important when there are a small number of clusters or the variability in cluster sizes is large. Constraining the randomisation on cluster size, where feasible, might mitigate this effect.

Project description:To systematically assess adherence of randomised trials in surgery to Consolidated Standards of Reporting Trials (CONSORT) guidelines for non-pharmacological treatments (NPT). Surgical trials are considered more difficult to design and execute than pharmacological trials. Furthermore, the original CONSORT statement does not address some aspects that are vital to the transparent reporting of surgical trials. The CONSORT-NPT extension was designed to address these issues but adherence in medical and surgical journals has not been assessed.Cross-sectional study.We identified eight general medical and eight surgical journals, indexed in PubMed and published in 2011, with the highest impact factors in their respective categories.Adherence to CONSORT statement and CONSORT-NPT extension items.We identified 54 surgical trials (22 published in medical journals and 32 in surgical journals). There were eight items for which there was less than 30% overall compliance (seven were specific to the CONSORT-NPT extension). These seven items are related to: a full description of the care providers, centres and blinding status in the abstract (n=7/54, 13%), eligibility criteria for centres performing the interventions (n=13/54, 24%), how adherence of care providers with the protocol was assessed or enhanced (n=7/54, 13%), how clustering by care providers or centres was addressed as it relates to sample size (n=3/54, 6%), how care providers were allocated to each group (n=9/54, 17%), how clustering by care providers or centres was addressed as it relates to statistical methods (n=2/54, 4%), a description of care providers (case volume, qualification, expertise, etc) and centres (volume) in each group (n=0/54, 0%).Adherence of surgical trials to CONSORT-NPT extension items is much poorer than to the standard CONSORT statement. Adherence also appears to be superior in general medical journals compared with surgical journals. Raising awareness and conducting qualitative research to identify areas for specific intervention will be important going forward.