Operational Difficulties with Internal Pilot Studies to Update Sample Size

Abstract

Internal pilot studies used for establishing the required sample size for a clinical trial part way through that trial are attractive when one is faced with difficulties in determining underlying variances or underlying event rates. By extrapolating a known curio ofpost-hoc sample size calculations, it is demonstrated how a sample size calculation may be obtained from a blind internal pilot that increases the study size even though, had a decision been made to stop the study and unblind it, enough information existed to reject the null hypothesis.

The questions of whether to continue recruiting and how much further to recruit may be considered. This will be influenced by the determination of the final (relative to the initial) study size determined from the internal pilot and the current perceived interest in the research question. If a study is stopped at the point of the recalculation, the reasons for the early stopping need to be carefully considered to decide if any bias may result. The decision to stop may be unconditional or conditional on the data. The two cases are distinguished through a variety of examples and their possible biases are considered.