Bmc Med Res Methodol
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Bmc Med Res Methodol · Jan 2012
Learning from failure--rationale and design for a study about discontinuation of randomized trials (DISCO study).
Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. ⋯ Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.
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Bmc Med Res Methodol · Jan 2012
ReviewA review of the reporting and handling of missing data in cohort studies with repeated assessment of exposure measures.
Retaining participants in cohort studies with multiple follow-up waves is difficult. Commonly, researchers are faced with the problem of missing data, which may introduce biased results as well as a loss of statistical power and precision. The STROBE guidelines von Elm et al. (Lancet, 370:1453-1457, 2007); Vandenbroucke et al. (PLoS Med, 4:e297, 2007) and the guidelines proposed by Sterne et al. (BMJ, 338:b2393, 2009) recommend that cohort studies report on the amount of missing data, the reasons for non-participation and non-response, and the method used to handle missing data in the analyses. We have conducted a review of publications from cohort studies in order to document the reporting of missing data for exposure measures and to describe the statistical methods used to account for the missing data. ⋯ This review highlights the inconsistent reporting of missing data in cohort studies and the continuing use of inappropriate methods to handle missing data in the analysis. Epidemiological journals should invoke the STROBE guidelines as a framework for authors so that the amount of missing data and how this was accounted for in the analysis is transparent in the reporting of cohort studies.
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Bmc Med Res Methodol · Jan 2012
Randomized Controlled Trial Comparative StudyTelephone follow-up to a mail survey: when to offer an interview compared to a reminder call.
Using a different mode of contact on the final follow-up to survey non-respondents is an identified strategy to increase response rates. This study was designed to determine if a reminder phone call or a phone interview as a final mode of contact to a mailed survey works better to increase response rates and which strategy is more cost effective. ⋯ The additional cost of completing an interview is worth it when an additional signed form is not required of the respondent. However, when such a signed form is required, offering an interview instead of a reminder phone call as a follow up to non-respondents does not increase response rates enough to outweigh the additional costs.
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Bmc Med Res Methodol · Jan 2012
Randomized Controlled TrialAlternative analyses for handling incomplete follow-up in the intention-to-treat analysis: the randomized controlled trial of balloon kyphoplasty versus non-surgical care for vertebral compression fracture (FREE).
Clinical trial participants may be temporarily absent or withdraw from trials, leading to missing data. In intention-to-treat (ITT) analyses, several approaches are used for handling the missing information - complete case (CC) analysis, mixed-effects model (MM) analysis, last observation carried forward (LOCF) and multiple imputation (MI). This report discusses the consequences of applying the CC, LOCF and MI for the ITT analysis of published data (analysed using the MM method) from the Fracture Reduction Evaluation (FREE) trial. ⋯ The FREE trial results are robust as the alternative methods used for substituting missing data produced similar results. The MM method showed the highest statistical precision suggesting it is the most appropriate method to use for analysing the FREE trial data.
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Bmc Med Res Methodol · Jan 2012
Bayesian model selection techniques as decision support for shaping a statistical analysis plan of a clinical trial: an example from a vertigo phase III study with longitudinal count data as primary endpoint.
A statistical analysis plan (SAP) is a critical link between how a clinical trial is conducted and the clinical study report. To secure objective study results, regulatory bodies expect that the SAP will meet requirements in pre-specifying inferential analyses and other important statistical techniques. To write a good SAP for model-based sensitivity and ancillary analyses involves non-trivial decisions on and justification of many aspects of the chosen setting. In particular, trials with longitudinal count data as primary endpoints pose challenges for model choice and model validation. In the random effects setting, frequentist strategies for model assessment and model diagnosis are complex and not easily implemented and have several limitations. Therefore, it is of interest to explore Bayesian alternatives which provide the needed decision support to finalize a SAP. ⋯ The proposed Bayesian methods are not only appealing for inference but notably provide a sophisticated insight into different aspects of model performance, such as forecast verification or calibration checks, and can be applied within the model selection process. The mean of the logarithmic score is a robust tool for model ranking and is not sensitive to sample size. Therefore, these Bayesian model selection techniques offer helpful decision support for shaping sensitivity and ancillary analyses in a statistical analysis plan of a clinical trial with longitudinal count data as the primary endpoint.