Abstract
BackgroundAlthough interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials.MethodsSource of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS) or progression free survival (PFS). A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a) general characteristics of the protocol b) disease localization and patient setting; c) study design d) interim analyses; e) DSMC.ResultsThe analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols), and the planning of interim analysis, without DSMC (14.7%).ConclusionThe results indicate that there is still insufficient attention paid to the implementation of interim analysis.
Highlights
Importance of interim analyses The simplest approach for evaluating results of a clinical trial is to plan just one statistical analysis at the end of the study, using a fixed-sample size design: planning and conduction are easy, and the methods for estimation are well established
The DAMOCLES working party2 addressed several different issues, using different methodological approaches: systematic literature reviews of data and safety monitoring committee (DSMC), small group processes in decision-making; sample surveys of reports of randomised clinical trials (RCTs), recently completed and still ongoing RCTs and policies of major organisations involved in RCTs; case studies of selected DSMCs; and interviews with experienced DSMC members
The results of these studies indicated that only about a quarter of main RCT reports mention use of a DSMC and wide variation exists in the structure and organisation of DSMCs, with little guidance on how they should operate
Summary
Importance of interim analyses The simplest approach for evaluating results of a clinical trial is to plan just one statistical analysis at the end of the study, using a fixed-sample size design: planning and conduction are easy, and the methods for estimation are well established This approach, which is convenient and effective when all observations are available in a short period of time, is less appropriate when data become available sequentially. The tasks of "external monitoring" are to evaluate data integrity, safety and efficacy of treatments and to provide advice on continuing the study as originally planned, or suggesting changes in its conduct, or even on stopping it This advice is mainly based on trial results, but should take into account the context of information external to the trial available at the moment of the analysis[1]. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials
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