In our latest blog of the series, we examine the topic of estimands with respect to clinical trials affected by the COVID-19 pandemic. When evaluating whether the primary objective of the trial is affected by the pandemic, it is necessary to consider the treatment effect in the absence of the COVID-19 pandemic and not confounded by pandemic-related events. This should be done via the estimands framework, looking at each of the five attributes of the estimand. It is critical to ensure that it is still possible to estimate the treatment effects aligned to the objectives and that the planned methods of analyses are still fully aligned to the estimands.
The Estimands Framework
Treatment Condition of Interest: This should remain the same as originally intended, although the pandemic may cause operational and logistical issues with study drug supply and delivery. Any pandemic-related issues with adherence to study drug and concomitant medications should be considered as intercurrent events.
Population: This should remain as originally intended to avoid deviating from the primary objective of the trial. However, consideration should be given to address the potential effect of COVID-19 vaccines, particularly in multi-region trials as COVID-19 vaccines became available at different times.
Variable: In most cases, the endpoint that is used to address the clinical question should remain as originally intended. If alternative data collection methods are required for the endpoint, it must be ensured that the endpoint is not compromised. All alternative data collection methods that are employed should be assessed for their potential effects on endpoint variability. Any different methods of collection that are used need to be comparable.