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Journal ArticleDOI

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

30 Jan 2013-PLOS ONE (Public Library of Science)-Vol. 8, Iss: 1
TL;DR: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results, however, no differences have been found in terms of impact factor.
Abstract: Objectives Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61–2·56) for studies with results classified as positive and 3·21 years (IC95 2·69–3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55–2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141–28·409) and negative result studies (median 8·266, interquartile range: 4·135–17·157). Conclusions Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.
Citations
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Journal ArticleDOI
TL;DR: Three main actions are warranted: academic institutions and funders should reward investigators who fully disseminate their research protocols, reports, and participant-level datasets, and standards for the content of protocols and full study reports should be rigorously developed and adopted for all types of health research.

668 citations

Journal ArticleDOI
TL;DR: The barriers that inhibit scientists from measuring the effects of AI and automation on the future of work are discussed and a decision framework that focuses on resilience to unexpected scenarios in addition to general equilibrium behavior is recommended.
Abstract: Rapid advances in artificial intelligence (AI) and automation technologies have the potential to significantly disrupt labor markets. While AI and automation can augment the productivity of some workers, they can replace the work done by others and will likely transform almost all occupations at least to some degree. Rising automation is happening in a period of growing economic inequality, raising fears of mass technological unemployment and a renewed call for policy efforts to address the consequences of technological change. In this paper we discuss the barriers that inhibit scientists from measuring the effects of AI and automation on the future of work. These barriers include the lack of high-quality data about the nature of work (e.g., the dynamic requirements of occupations), lack of empirically informed models of key microlevel processes (e.g., skill substitution and human–machine complementarity), and insufficient understanding of how cognitive technologies interact with broader economic dynamics and institutional mechanisms (e.g., urban migration and international trade policy). Overcoming these barriers requires improvements in the longitudinal and spatial resolution of data, as well as refinements to data on workplace skills. These improvements will enable multidisciplinary research to quantitatively monitor and predict the complex evolution of work in tandem with technological progress. Finally, given the fundamental uncertainty in predicting technological change, we recommend developing a decision framework that focuses on resilience to unexpected scenarios in addition to general equilibrium behavior.

256 citations

Journal ArticleDOI
TL;DR: It appears that accelerometers still have limitations regarding generalisability, validity, comprehensiveness, simplicity, affordability, adaptability, between-study comparability and sustainability, and the widespread adoption of accelerometers specifically for large-scale PA surveillance systems may be premature.
Abstract: Objective Self-reports of physical activity (PA) have been the mainstay of measurement in most non-communicable disease (NCD) surveillance systems. To these, other measures are added to summate to a comprehensive PA surveillance system. Recently, some national NCD surveillance systems have started using accelerometers as a measure of PA. The purpose of this paper was specifically to appraise the suitability and role of accelerometers for population-level PA surveillance. Methods A thorough literature search was conducted to examine aspects of the generalisability, reliability, validity, comprehensiveness and between-study comparability of accelerometer estimates, and to gauge the simplicity, cost-effectiveness, adaptability and sustainability of their use in NCD surveillance. Conclusions Accelerometer data collected in PA surveillance systems may not provide estimates that are generalisable to the target population. Accelerometer-based estimates have adequate reliability for PA surveillance, but there are still several issues associated with their validity. Accelerometer-based prevalence estimates are largely dependent on the investigators’ choice of intensity cut-off points. Maintaining standardised accelerometer data collections in long-term PA surveillance systems is difficult, which may cause discontinuity in time-trend data. The use of accelerometers does not necessarily produce useful between-study and international comparisons due to lack of standardisation of data collection and processing methods. To conclude, it appears that accelerometers still have limitations regarding generalisability, validity, comprehensiveness, simplicity, affordability, adaptability, between-study comparability and sustainability. Therefore, given the current evidence, it seems that the widespread adoption of accelerometers specifically for large-scale PA surveillance systems may be premature.

254 citations

Journal ArticleDOI
TL;DR: The present review provides a thorough and detailed account of the current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide–protein interactions and focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function.
Abstract: Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world yet it also presents a grave challenge: as more people survive into later life, more also experience the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective novel treatments are still lacking. Alternative drug development strategies are now being explored, such as the repurposing of existing drugs used to treat other diseases. This can save a considerable amount of time and money since the pharmacokinetics, pharmacodynamics and safety profiles of these drugs are already established, effectively enabling preclinical studies to be bypassed. Metformin is one such drug currently being investigated for novel applications. The present review provides a thorough and detailed account of our current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide–protein interactions. It also focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function. Research in this area holds the key to solving many of the mysteries of our current understanding of drug action and concerted effects to provide sustained and long-life health.

220 citations

Journal ArticleDOI
TL;DR: The sociodemographic, psychosocial, health status, treatment-related and intervention-related determinants are interlinked and contribute to optimal adherence and Clinics providing ART in SSA should design targeted interventions addressing these determinants to optimise health outcomes.
Abstract: Objective The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of patients at high risk of suboptimal adherence and targeted interventions. The aim of this review was to identify and summarise determinants of adherence to ART among HIV-positive adults. Design Systematic review of adherence to ART in SSA from January 2002 to October 2014. Methods A systematic search was performed in 6 databases (PubMed, Cochrane Library, EMBASE, Web of Science, Popline, Global Health Library) for qualitative and quantitative articles. Risk of bias was assessed. A meta-analysis was conducted for pooled estimates of effect size on adherence determinants. Results Of the 4052 articles screened, 146 were included for final analysis, reporting on determinants of 161 922 HIV patients with an average adherence score of 72.9%. Main determinants of non-adherence were use of alcohol, male gender, use of traditional/herbal medicine, dissatisfaction with healthcare facility and healthcare workers, depression, discrimination and stigmatisation, and poor social support. Promoters of adherence included counselling and education interventions, memory aids, and active disclosure among people living with HIV. Determinants of health status had conflicting influence on adherence. Conclusions The sociodemographic, psychosocial, health status, treatment-related and intervention-related determinants are interlinked and contribute to optimal adherence. Clinics providing ART in SSA should therefore design targeted interventions addressing these determinants to optimise health outcomes.

209 citations

References
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Journal ArticleDOI
TL;DR: A systematic review and meta-analysis of placebo-controlled studies examined the efficacy and tolerability of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products in adults with somatoform disorders in adults to improve optimal treatment decisions.
Abstract: BACKGROUND: Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions.OBJECTIVES: To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults.SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation {\&} Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field.SELECTION CRITERIA: We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder.DATA COLLECTION AND ANALYSIS: One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment.MAIN RESULTS: We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95{\%} CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2{\%}; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95{\%} CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63{\%}). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95{\%} CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0{\%}).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42{\%}; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0{\%}).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95{\%} CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23{\%}).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95{\%} CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0{\%}; low-quality evidence) or NPs and placebo (RR 0.85, 95{\%} CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0{\%}; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95{\%} CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14{\%}; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95{\%} CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0{\%}; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0{\%} to 32{\%}), but low for NPs (0{\%} to 1.7{\%}).The risk of bias was high in many domains across studies. Seventeen trials (65.4{\%}) gave no information about random sequence generation and only two (7.7{\%}) provided information about allocation concealment. Eighteen studies (69.2{\%}) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise.AUTHORS' CONCLUSIONS: The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found.Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety.

11,458 citations

Journal ArticleDOI
28 Aug 1996-JAMA
TL;DR: For RCTs to ultimately benefit patients, the published report should be of the highest possible standard and should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial.
Abstract: THE RANDOMIZED controlled trial (RCT), more than any other methodology, can have a powerful and immediate impact on patient care. Ideally, the report of such an evaluation needs to convey to the reader relevant information concerning the design, conduct, analysis, and generalizability of the trial. This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial. Accurate and complete reporting also benefits editors and reviewers in their deliberations regarding submitted manuscripts. For RCTs to ultimately benefit patients, the published report should be of the highest possible standard. For editorial comment see p 649. Evidence produced repeatedly over the last 30 years indicates a wide chasm between what a trial should report and what is actually published in the literature. In a review of 71 RCTs with negative results published between 1960 and 1975, the authors reported that the vast

3,197 citations

Journal ArticleDOI
TL;DR: The presence of publication bias in a cohort of clinical research studies is confirmed and it is suggested that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies.

2,800 citations


"Positive Outcomes Influence the Rat..." refers result in this paper

  • ...Previous studies, performed in different areas of clinical research, including basic experimental studies, observational studies, and clinical trials, have shown the existence of a positive association between publication rates and favorable outcomes [8–12]....

    [...]

  • ...Previous research has documented the existence of lower publication rates [8–12] and delay of publication [9], [13] in studies with negative outcomes in comparison with studies with positive outcomes....

    [...]

Journal ArticleDOI
TL;DR: For RCTs to ultimately benefit patients, the published report should be of the highest possible standard and accurate and complete reporting is needed.

1,662 citations

Journal ArticleDOI
26 May 2004-JAMA
TL;DR: The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols and Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention.
Abstract: ContextSelective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.ObjectiveTo study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.DesignCohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.Main Outcome MeasuresCompleteness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.ResultsOne hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.ConclusionsThe reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.

1,638 citations