Abstract
BackgroundPublicly funded trials regularly fail to recruit their target sample size or find a significant positive result. Adaptive clinical trials which may partly mediate against the problems are not often applied. In this paper we investigate the potential of a form of adaption in a clinical trial - a futility analysis - to see if it has potential to improve publicly funded trials.MethodsOutcome data from trials funded by two UK bodies, the Health Technology Assessment (HTA) programme and the UK Medical Research Council (MRC), were collected. These data were then used to simulate each trial with a single futility analysis using conditional power, undertaken after 50% to 90% of the patients had been recruited. Thirty-three trials recruiting between 2002 and 2008 met the inclusion criteria. Stopping boundaries of conditional powers of 20%, 30% and 40% were considered and outcomes included the number of trials successfully stopped and number of patients saved.ResultsInclusion of a futility analysis after 75% of the patients had been recruited would have potentially resulted in 10 trials, which went on to have negative results, correctly stopping for futility using a stopping boundary of 30%. A total of 807 patients across all the trials would potentially have been saved using these futility parameters. The proportion of studies successfully recruiting would also have increased from 45% to 64%.ConclusionsA futility assessment has the potential to increase efficiency, save patients and decrease costs in publicly funded trials. While there are logistical issues in undertaking futility assessments we recommend that investigators should aim to include a futility analysis in their trial design wherever possible.
Highlights
Funded trials regularly fail to recruit their target sample size or find a significant positive result
Publicly funded trials in the United Kingdom (UK) have poor rates of recruitment [1,2], with only just over half successfully recruiting to their initial target sample size
One trial had low conditional power towards the end of recruitment despite finding an effect larger than planned: this is due to the lack of statistical significance found by the trial, that is P-values of P = 0.050 [7]
Summary
Funded trials regularly fail to recruit their target sample size or find a significant positive result. Adaptive clinical trials which may partly mediate against the problems are not often applied. Funded trials in the United Kingdom (UK) have poor rates of recruitment [1,2], with only just over half successfully recruiting to their initial target sample size. A consequence of poor recruitment is that a trial can have reduced power. Trials with poor recruitment may be more likely to request an extension to attempt to reach their target sample size. Between 2002 and 2008 nearly half of all publicly funded trials received an extension of some kind [1], with similar results found between 1994 and 2002 [2]. The extension may be either time-based, cost-based or both
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