Box 20.

Exemplars on reporting item 14b

Example 1. 2-stage AD with options for futility and efficacy early stopping and increase in sample size; unplanned trial termination “The planned interim analysis of the study was done in November 2005 after 125 patients have been (sic) recruited.… According to the adaptive design of the study, we therefore calculated another 163 patients per treatment group to be required to answer the primary question. Upon the slow accrual up to that timepoint, the study coordinators decided to close the trial at the end of 2005. Further analysis was regarded to be exploratory.” [194] Example 2. Sequential-step AD; unplanned trial termination “…the third interim analysis indicated unexpectedly low initial cure rates in both arms; 84% in the multiple dose and 73% in the single-dose arm. The stopping rule was not met …, but based on the observed poor efficacy overall, and following discussions with the Data Safety and Monitoring Board (DSMB) and investigators, the sponsor terminated the trial.” [262]