Trial participants withdraw from therapy or cross over between treatment groups

Differential withdrawal rates between study arms in a trial may complicate interpretation of the findings, especially if there is divergence between intention-to-treat and on-treatment results. If study participants cross over between treatment groups after reaching a study endpoint (for example, disease progression in cancer) the ability of the trial to report unbiased comparisons for longer-term ‘effectiveness’ outcomes (for example, overall survival) is compromised.