Changing interim monitoring in response to internal clinical trial data.

ABSTRACT

Designing clinical trials for emerging infectious diseases such as COVID-19 is challenging because information needed for proper planning may be lacking. Pre-specified adaptive designs can be attractive options, but what happens if a trial with no such design needs to be modified? For example, unexpectedly high efficacy (approximately 95%) in two COVID-19 vaccine trials might cause investigators in other COVID-19 vaccine trials to increase the number of interim analyses to allow earlier stopping for efficacy. If such a decision is based solely on external data, there are no issues, but what if internal trial data by arm are also examined? Fortunately, the conditional error principle of Müller and Schäfer (2004) can be used to ensure no inflation of the type 1 error rate, even if no interim analyses were planned. We study the properties, including limitations, of this method. We provide a shiny app to evaluate changes in timing of interim analyses in response to outcome data by arm in clinical trials.