Issues in data-monitoring for complex clinical trials

During a clinical trial, accruing data is often seen in confidence by a data monitoring committee to evaluate whether early termination of the study or other modifications are needed in the light of emerging results. For a classical two-group trial with a single primary endpoint there are well-established statistical approaches. However, more complex trials, such as platform trials or trials with multiple endpoints, present different challenges. Such designs are now being used more regularly, including during the recent COVID-19 pandemic wher they rapidly informed clincal practice. We review these designs and current approaches to data-monitoring, as well as challenges that are emerging, and outline where further developments are needed.