Abstract
Sample size justification is an important consideration when planning a clinical trial, not only for the main trial but also for any preliminary pilot trial. When the outcome is a continuous variable, the sample size calculation requires an accurate estimate of the standard deviation of the outcome measure. A pilot trial can be used to get an estimate of the standard deviation, which could then be used to anticipate what may be observed in the main trial. However, an important consideration is that pilot trials often estimate the standard deviation parameter imprecisely. This paper looks at how we can choose an external pilot trial sample size in order to minimise the sample size of the overall clinical trial programme, that is, the pilot and the main trial together. We produce a method of calculating the optimal solution to the required pilot trial sample size when the standardised effect size for the main trial is known. However, as it may not be possible to know the standardised effect size to be used prior to the pilot trial, approximate rules are also presented. For a main trial designed with 90% power and two-sided 5% significance, we recommend pilot trial sample sizes per treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (≤0.1), small (0.2), medium (0.5) or large (0.8), respectively.
Highlights
Sample size is an important consideration when a clinical trial is planned, for the main trial and for any preliminary pilot trial
If we investigate how much larger the sample size estimate is from this approach compared to the standard approach, by dividing equation (3) by equation (1) with s2 used as an estimate of 2, we find that the approach sample size is larger by a factor of the factor by which the upper confidence limit (UCL) approach sample size is greater than the standard approach depends only upon the pilot trial sample size and the value of X
Other methods fail to recognise this point and aim to minimise both the pilot and the main trials separately which could lead to the suboptimal sample size overall
Summary
Sample size is an important consideration when a clinical trial is planned, for the main trial and for any preliminary pilot trial. As pilot trials do not have the same objectives as a main trial, setting the sample size in the same way – using formal power considerations – is usually not necessary. It is still necessary to provide a sample size justification even when the reasons for choosing a particular size are pragmatic
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