Differential dropout and bias in randomised controlled trials: when it matters and when it may not

Abstract

Dropout in randomised controlled trials is common and threatens the validity of results, as completers may differ from people who drop out. Differing dropout rates between treatment arms is sometimes called differential dropout or attrition. Although differential dropout can bias results, it does not always do so. Similarly, equal dropout may or may not lead to biased results. Depending on the type of missingness and the analysis used, one can get a biased estimate of the treatment effect with equal dropout rates and an unbiased estimate with unequal dropout rates. We reinforce this point with data from a randomised controlled trial in patients with renal cancer and a simulation study.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Quality of life (QoL) stratified by treatment arm and dropout time. Possible range of QoL=0-100, with higher values indicating better QoL. If data were missing completely at random (MCAR), the within arm trajectories would be indistinguishable. As patients with lower baseline QoL are more likely drop out, these data are not MCAR