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

ObjectiveRandomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients’ preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined.DesignSystematic review and meta-analyses.Data sourcesMEDLINE, Embase, PsycINFO and the Cochrane Library.Eligibility criteria for selecting studiesRPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included.Data extraction and synthesisTwo independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed.ResultsIn total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%–100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%–99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI −0.178 to 0.364, p=0.502).ConclusionsPatients’ preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs.PROSPERO registration numberCRD42019094438.

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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

HRB Open Research ◽

10.12688/hrbopenres.13122.1 ◽

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.

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Long-term child follow-up after large obstetric randomised controlled trials for the evaluation of perinatal interventions: a systematic review of the literature

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2012.03465.x ◽

2012 ◽

Vol 120 (1) ◽

pp. 15-22 ◽

Cited By ~ 19

Author(s):

MJ Teune ◽

AG van Wassenaer ◽

GL Malin ◽

E Asztalos ◽

Z Alfirevic ◽

...

Keyword(s):

Systematic Review ◽

Randomised Controlled Trials ◽

Controlled Trials ◽

Review Of The Literature ◽

Randomised Controlled

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Which treatment is most effective for patients with Achilles tendinopathy? A living systematic review with network meta-analysis of 29 randomised controlled trials

British Journal of Sports Medicine ◽

10.1136/bjsports-2019-101872 ◽

2020 ◽

pp. bjsports-2019-101872 ◽

Cited By ~ 3

Author(s):

Arco C van der Vlist ◽

Marinus Winters ◽

Adam Weir ◽

Clare L Ardern ◽

Nicky J Welton ◽

...

Keyword(s):

Systematic Review ◽

Exercise Therapy ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Achilles Tendinopathy ◽

Risk Of Bias ◽

Controlled Trials ◽

Wait And See ◽

Randomised Controlled

ObjectiveTo provide a consistently updated overview of the comparative effectiveness of treatments for Achilles tendinopathy.DesignLiving systematic review and network meta-analysis.Data sourcesMultiple databases including grey literature sources were searched up to February 2019.Study eligibility criteriaRandomised controlled trials examining the effectiveness of any treatment in patients with both insertional and/or midportion Achilles tendinopathy. We excluded trials with 10 or fewer participants per treatment arm or trials investigating tendon ruptures.Data extraction and synthesisReviewers independently extracted data and assessed the risk of bias. We used the Grading of Recommendations Assessment, Development and Evaluation to appraise the certainty of evidence.Primary outcome measureThe validated patient-reported Victorian Institute of Sport Assessment-Achilles questionnaire.Results29 trials investigating 42 different treatments were included. 22 trials (76%) were at high risk of bias and 7 (24%) had some concerns. Most trials included patients with midportion tendinopathy (86%). Any treatment class seemed superior to wait-and-see for midportion Achilles tendinopathy at 3 months (very low to low certainty of evidence). At 12 months, exercise therapy, exercise+injection therapy and exercise+night splint therapy were all comparable with injection therapy for midportion tendinopathy (very low to low certainty). No network meta-analysis could be performed for insertional Achilles tendinopathy.Summary/conclusionIn our living network meta-analysis no trials were at low risk of bias and there was large uncertainty in the comparative estimates. For midportion Achilles tendinopathy, wait-and-see is not recommended as all active treatments seemed superior at 3-month follow-up. There seems to be no clinically relevant difference in effectiveness between different active treatments at either 3-month or 12-month follow-up. As exercise therapy is easy to prescribe, can be of low cost and has few harms, clinicians could consider starting treatment with a calf-muscle exercise programme.PROSPERO registration numberCRD42018086467.

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