5,900 research outputs found
A systematic review identifies shortcomings in the reporting of crossover trials in chronic painful conditions
No full textObjectives: To investigate the reporting of study features of interest in abstracts and full texts of journal publications of crossover trials in chronic painful conditions. Study Design and Setting: Systematic review based on a MEDLINE (PubMed) search (January 1990-August 2014). Results: Ninety-eight publications on crossover studies with 3,513 study participants were eligible for inclusion. Double-blind status and randomized allocation to treatment groups are commonly reported in both abstracts and full texts (90 of 98 publications and 82 of 98 publications, respectively). Adverse events are reported in both abstract and full text in 49 of 98 publications and in the full text only in 44 of 98. A breakdown of results by treatment period is provided only in 23 of 98 publications, and if so, is reported only in the full text, never in the abstract. There is a time trend for the reporting of randomization in abstracts; it is more likely to be reported in recent studies (P = 0.0094). No time trends are detected in the reporting of double-blind status (P = 0.1087) and adverse events (P = 0.6084). Conclusion: The reporting of adverse events in the abstract and the reporting of results specified by crossover period in the full texts of journal publications on crossover pain trials should be improved. (C) 2015 Published by Elsevier Inc.Daiichi Sankyo, Inc
Using the internet in the management of multiple sclerosis: an overview of the evidence available
No full textUsing the internet in the management of multiple sclerosis: an overview of the evidence available
No full textWork-related outcomes in randomised placebo-controlled pain trials: a systematic review and meta-analysis
No full textBackground: Chronic painful conditions have an important influence on the ability to work. Work-related outcomes, however, are not commonly reported in publications on trials investigating the treatment of chronic painful conditions. We aim to provide an overview of the reporting of work-related outcomes in such trials and investigate the relationship between work-related outcomes and pain outcomes. Methods: We conducted a systematic literature search in PubMed with the aim of identifying randomised placebo-controlled clinical trials investigating treatments for chronic painful conditions or rheumatic diseases that also reported on work-related outcomes. Methodological study quality was assessed with the Oxford Quality Scale (OQS). Meta-analyses were conducted for the outcomes of interference with work and number of patients with at least 30% reduction in pain intensity (30% pain responders). The correlation between work-related and pain outcomes was investigated with regression analyses. Results: We included 31 publications reporting on 27 datasets from randomised placebo-controlled trials (with a total of 11,434 study participants) conducted in chronic painful or rheumatic diseases and reporting on work-related outcomes. These 31 publications make up only about 0.2% of all publications on randomised placebo-controlled trials in such conditions. The methodological quality of the included studies was high; only nine studies scored less than four (out of a maximum five) points on the OQS. Sixteen different work-related outcomes were reported on in the studies. Of 25 studies testing for the statistical significance of changes in work-related outcomes over the course of the trials, 14 (56%) reported a significant improvement; the others reported non-significant changes. Eight studies reported data on both interference with work and 30% pain responders: meta analyses demonstrated similar, statistically significant improvements in both these outcomes with active therapy compared to placebo and regression analysis showed that these outcomes were correlated. Conclusions: Despite the importance of pain as a reason for decreased ability to work, work-related outcomes are reported in substantially less than 1% of publications on placebo-controlled trials in chronic painful and rheumatic diseases. Work-related outcomes and pain responder outcomes are closely related.Pfizer; Reckitt-Benckise
Trends in annualized relapse rates in relapsing–remitting multiple sclerosis and consequences for clinical trial design
No full text Background: Sample size calculation is a key aspect in the planning of any trial. Planning a randomized placebo-controlled trial in relapsing–remitting multiple sclerosis (RRMS) requires knowledge of the annualized relapse rate (ARR) in the placebo group. Objectives: This paper aims (i) to characterize the uncertainty in ARR by conducting a systematic review of placebo-controlled, randomized trials in RRMS and by modelling the ARR over time; and (ii) to assess the feasibility and utility of blinded sample size re-estimation (BSSR) procedures in RRMS. Methods: A systematic literature review was carried out by searching PubMed, Ovid Medline and the Cochrane Register of Controlled Trials. The placebo ARRs were modelled by negative binomial regression. Computer simulations were conducted to assess the utility of BSSR in RRMS. Results: Data from 26 placebo-controlled randomized trials were included in this analysis. The placebo ARR decreased by 6.2% per year ( p < 0.0001; 95% CI (4.2%; 8.1%)) resulting in substantial uncertainty in the planning of future trials. BSSR was shown to be feasible and to maintain power at a prespecified level also if the ARR was misspecified in the planning phase. Conclusions: Our investigations confirmed previously reported trends in ARR. In this context adaptive strategies such as BSSR designs are recommended for consideration in the planning of future trials in RRMS. </jats:p
Changing EDSS Progression in Placebo Cohorts in Relapsing MS: A Systematic Review and Meta-Regression
No full textBackground
Recent systematic reviews of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS) revealed a decrease in placebo annualized relapse rates (ARR) over the past two decades. Furthermore, regression to the mean effects were observed in ARR and MRI lesion counts. It is unclear whether disease progression measured by the expanded disability status scale (EDSS) exhibits similar features.
Methods
A systematic review of RCTs in RMS was conducted extracting data on EDSS and baseline characteristics. The logarithmic odds of disease progression were modelled to investigate time trends. Random-effects models were used to account for between-study variability; all investigated models included trial duration as a predictor to correct for unequal study durations. Meta-regressions were conducted to assess the prognostic value of a number of study-level baseline variables.
Results
The systematic literature search identified 39 studies, including a total of 19,714 patients. The proportion of patients in placebo controls experiencing a disease progression decreased over the years (p<0.001). Meta-regression identified associated covariates including the size of the study and its duration that in part explained the time trend. Progression probabilities tended to be lower in the second year of a study compared to the first year with a reduction of 28% in progression odds from year 1 to year 2 (p = 0.017).
Conclusion
EDSS disease progression exhibits similar behaviour over time as the ARR and point to changes in trial characteristics over the years. This needs to be considered in comparisons between historical and recent trials
Comparison of disability scores and annualised relapse rates as trial outcomes in randomized, placebo controlled trials in relapsing multiple sclerosis: a systematic review
No full textComparison of disability scores and annualised relapse rates as trial outcomes in randomized, placebo controlled trials in relapsing multiple sclerosis: a systematic review
No full textDo dolphins benefit from nonlinear mathematics when processing their sonar returns?
No full textAn interview with author Tim Leighton about the paper
Time-patterns of annualized relapse rates in randomized placebo-controlled clinical trials in relapsing multiple sclerosis: A systematic review and meta-analysis
No full textBackground: Although it is known that the annualized relapse rate (ARR) in patients with multiple sclerosis (MS) changes as disease progresses, in the design and analysis of trials in relapsing multiple sclerosis (RMS) constant ARRs are assumed. Objectives: This paper aims to assess time-patterns of trial ARR by conducting a systematic review of randomized, placebo-controlled trials in RMS. Methods: A systematic literature search was conducted by searching PubMed for randomized, placebo-controlled trials in RMS. In meta-analyses the following comparisons of trial ARR were carried out for the placebo controls and active treatment arms: months 1-6 vs. months 7-12, and months 1-12 vs. months 13-24. Results: A total of 52 trials was identified. Out of these, information on the time-dependence of trial ARR could be extracted from 13 trials. The ARR was by 25% (p = 0.0005) and 40% (p < 0.0001) higher in months 1-12 compared with months 13-24 for placebo and active treatments, respectively. Consequently, the treatment effects were by 13% (p = 0.23) larger in the second year compared with the first year. Within the first year of follow-up the ARR was by 4% (p = 0.75) and 23% (p = 0.06) higher in months 1-6 compared with months 7-12 for placebo controls and active arms, respectively. Conclusions: Trial ARR decreases during a trial in RMS, which is in line with epidemiological findings and has implications for design and analysis of future trials. The observed decrease in trial ARR might be at least partially explained by regression to the mean. Individual patient data analyses are warranted
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