  Indolent cancers are characterized by long overall survival (OS) times.
Therefore, powering a clinical trial to provide definitive assessment of the
effects of an experimental intervention on OS in a reasonable timeframe is
generally infeasible. Instead, the primary outcome in many pivotal trials is an
intermediate clinical response such as progression-free survival (PFS). In
several recently reported pivotal trials of interventions for indolent cancers
that yielded promising results on an intermediate outcome, however, more mature
data or post-approval trials showed concerning OS trends. These problematic
results have prompted a keen interest in quantitative approaches for monitoring
OS that can support regulatory decision-making related to the risk of an
unacceptably large detrimental effect on OS. For example, the US Food and Drug
Administration, the American Association for Cancer Research, and the American
Statistical Association recently organized a one-day multi-stakeholder workshop
entitled 'Overall Survival in Oncology Clinical Trials'. In this paper, we
propose OS monitoring guidelines tailored for the setting of indolent cancers.
Our pragmatic approach is modeled, in part, on the monitoring guidelines the
FDA has used in cardiovascular safety trials conducted in Type 2 Diabetes
Mellitus. We illustrate proposals through application to several examples
informed by actual case studies.
