A Critical Look At Time-To-Event Analysis In Oncology Through The Prism Of Estimands

In oncology clinical trials, time-to-event endpoints, such as overall survival (OS), progression-free survival (PFS), event-free survival (EFS), disease-free survival (DFS), are crucial when it comes to the reliable estimation of treatment effects and determining the benefit of therapies under investigation.

Potential intercurrent events which typically need to be considered when planning a clinical trial in oncology include: discontinuation of treatment due to toxicity, clinical progression, initiation of new anti-cancer therapy (including switching between treatment arms), surgery, non-disease-related deaths and occurrence of second primary malignancies in adjuvant settings.

Often, several sensitivity analyses are carried out with different censoring rules, in line with the FDA guideline “Clinical Trial Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics”, in which tables with potential analyses of PFS for primary or sensitivity analyses were provided in the appendices.

In light of the new ICH E9R(1) Addendum on Estimands and Sensitivity Analysis, several sensitivity analyses are now regarded as supplementary analyses. Estimands are a systematic description of the treatment effect to be quantified in order to answer a trial's research objective. The estimand consists of the following five attributes: treatment, population, variable, population-level summary, and handling of intercurrent events (ICEs).

Learn about these changes in different censoring rules and how specifying appropriate estimands can affect oncology clinical trials.