scholarly journals Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e017240 ◽  
Author(s):  
Jianrong Zhang ◽  
Yiyin Zhang ◽  
Shiyan Tang ◽  
Long Jiang ◽  
Qihua He ◽  
...  
Keyword(s):  
Literature Review ◽  
Correlation Analysis ◽  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Solid Tumours ◽  
Phase Iii ◽  
Controlled Trials ◽  
Systematic Bias ◽  
Randomised Controlled ◽  
Local Assessment

ObjectiveUnbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).ConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.

scholarly journals Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review

BMJ ◽  
2012 ◽  
Vol 344 (may18 1) ◽  
pp. e2809-e2809 ◽  
Author(s):  
E. A. Akl ◽  
M. Briel ◽  
J. J. You ◽  
X. Sun ◽  
B. C. Johnston ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Controlled Trials ◽  
Potential Impact ◽  
Randomised Controlled ◽  
Lost To Follow Up

scholarly journals The impact of a run-in period on treatment effects in cardiovascular prevention randomised control trials: A protocol for a comprehensive review and meta-analysis

2020 ◽  
Vol 3 ◽  
pp. 82
Author(s):  
Robert Murphy ◽  
Emer McGrath ◽  
Aoife Nolan ◽  
Andrew Smyth ◽  
Michelle Canavan ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Cardiovascular Prevention ◽  
Controlled Trials ◽  
Loss To Follow Up ◽  
Relative Risks ◽  
Prevention Trials ◽  
Randomised Controlled

Background: A run-in period is often employed in randomised controlled trials to increase adherence to the intervention and reduce participant loss to follow-up in the trial population. However, it is uncertain whether use of a run-in period affects the magnitude of treatment effect. Methods: We will conduct a sensitive search for systematic reviews of cardiovascular preventative trials and a complete meta-analysis of treatment effects comparing cardiovascular prevention trials using a run-in period (“run-in trials”) with matched cardiovascular prevention trials that did not use a run-in period (“non-run-in trials”). We describe a comprehensive matching process which will match run-in trials with non-run-in trials by patient populations, interventions, and outcomes. For each pair of run-in trial and matched non-run-in trial(s), we will estimate the ratio of relative risks and 95% confidence interval. We will evaluate differences in treatment effect between run-in and non-run-in trials and our and our priamry outcome will be the ratio of relative risks for matched run-in and non-run-in trials for their reported cardiovascular composite outcome. Our secondary outcomes are comparisons of mortality, loss to follow up, frequency of adverse events and methodological quality of trials. Conclusions: This study will answer a key question about what influence a run-in period has on the magnitude of treatment effects in randomised controlled trials for cardiovascular prevention therapies.

scholarly journals The role of animal-assisted therapy in the management of people with dementia: a systematic literature review

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S276-S276
Author(s):  
Syed Nabeel Javaid
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Randomised Controlled Trials ◽  
Animal Assisted Therapy ◽  
Controlled Trials ◽  
People With Dementia ◽  
Randomised Controlled

AimsThe aim of this systematic literature review was to determine the evidence-based effectiveness of animal assisted interventions and to look at the factors that limit implementation of this intervention.BackgroundDementia is a major health issue worldwide impacting not only on the people diagnosed with dementia, but also on their families and caregivers, and the healthcare professionals. The symptoms of dementia include cognitive impairment that can range from mild to severe, and behavioural and psychological symptoms which have debilitating effects on functional capacity and quality of life. A number of non-pharmacological interventions are being developed to help people with dementia. Animal assisted therapy is one of those interventions that has demonstrated positive effects on various aspects of dementia (Filan and Llewellyn-Jones, 2006). However, there are limitations to its use and feasibility of animal assisted therapy programmes is unclear.MethodOnly randomised-controlled trials (RCTs) were to be included to evaluate high quality evidence. A systematic literature search was carried out to find using the PubMed and Cochrane databases and a search of the NICE website. Literature was screened according to inclusion and exclusion criteria. Eight randomised-controlled trials were selected to be used in this systematic review to assess the effectiveness of animal-assisted therapy.ResultThe results regarding the effectiveness of animal assisted therapy were variable. There was some improvement demonstrated in symptoms of depression, agitation, behaviour and cognitive impairment. Quality of life and activities of daily living also demonstrated positive outcomes. There was a reduction in the risk of falls in people with dementia. However, the studies conducted demonstrated limited methodologies. The factors limiting the use of animal assisted therapy were found to be concerns around adverse events to animals, issues of animal welfare and economic feasibility of animal assisted therapy programmes.ConclusionFurther research needs to be done using properly conducted randomised controlled trials with larger sample sizes to formally assess people's perceptions regarding therapy animals and develop clear guidelines and protocols for integrating these interventions in healthcare.

scholarly journals Impact of season and geography on CompEx Asthma: a composite end-point for exacerbations

2020 ◽  
Vol 6 (4) ◽  
pp. 00246-2020
Author(s):  
Alexandra Jauhiainen ◽  
Lieke E.J.M. Scheepers ◽  
Anne L. Fuhlbrigge ◽  
Tim Harrison ◽  
James Zangrilli ◽  
...  
Keyword(s):  
Eastern Europe ◽  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Statistical Significance ◽  
Fold Increase ◽  
Controlled Trials ◽  
End Point ◽  
Geographical Regions ◽  
Randomised Controlled ◽  
Event Rates

BackgroundCompEx Asthma, a novel composite end-point combining severe exacerbations (SevEx) with asthma-worsening events, was recently developed. Further characterisation of CompEx Asthma is needed to illustrate the applicability of this end-point. The objective was to evaluate CompEx Asthma as a rate end-point to determine how seasonal and geographical factors impact this novel outcome.MethodsSeven 24–56-week randomised controlled trials of budesonide/formoterol (BUD/FORM) and benralizumab were analysed. Annualised event rates (AERs) and treatment effects (hazard ratio (HR)) were analysed with Poisson and Andersen–Gill models, respectively. Seasonality was analysed by month and five geographical regions were evaluated.ResultsThe studies included 10 815 patients (63% female, mean age 42–49 years). CompEx Asthma AER mirrored seasonal variations in SevEx AER. CompEx Asthma AERs were higher versus SevEx in BUD/FORM and benralizumab trials (range 2.7–4.5-fold and 1.3–2.0-fold increase, respectively) and were less variable versus SevEx between regions (ratios of greatest:smallest AERs: 1.36 for CompEx versus 2.28 for SevEx (BUD/FORM); 1.81 for CompEx versus 2.22 for SevEx (benralizumab)). Treatment effects for CompEx Asthma and SevEx were generally similar across regions and months. However, in Eastern Europe, where SevEx rates were lowest, treatment effect was greater with CompEx Asthma versus SevEx, reaching statistical significance in the benralizumab studies (HR (95% CI): 0.67 (0.53–0.85) versus 0.87 (0.65–1.15)).ConclusionThis study confirmed the reliability of CompEx Asthma as a rate end-point and allowed detection of variations in seasonal SevEx rates, reduction of variation in rates across regions and potential greater sensitivity to treatment effects.

scholarly journals Randomised controlled trials: evaluating and communicating treatment effects

BMJ ◽  
2014 ◽  
Vol 348 (mar07 4) ◽  
pp. g1905-g1905
Author(s):  
P. Sedgwick ◽  
K. Joekes
Keyword(s):  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Controlled Trials ◽  
Randomised Controlled
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