OBJECTIVES: TTD in HRQoL is a common endpoint in oncology trials. A previous targeted literature review (TLR; Skaltsa et al. VIH 2018) of TTD definitions in NSCLC trials revealed that time to first deterioration without confirmation was the most frequently used definition with only few studies requiring confirmation, and none definitive deterioration. Our aim is to identify current practices and assess potential updates.

METHODS: An update of the previously conducted TLR of TTD definitions in NSCLC trials was performed. Searched databases included Ovid Embase and Medline. Searches were restricted from 2017 to March 2022 and publications included in previous TLR excluded. ClinicalTrials.Gov Registry was consulted for potentially further information on the TTD definition in the identified trials.

RESULTS: The searches identified 89 publications on NSCLC with 72 (covering 45 trials) included in the TLR. First deterioration was reported in 44% (20/45) of trials, confirmed deterioration in 36% (16/45), and definitive deterioration in 11% (5/45). No TTD definition was reported in 18% (8/45) of trials. The number of thresholds was reported for 38 trials, with only one reporting >1 thresholds. Nine trials (20%; 9/45) included death as an event or as confirmation, while no trial considered disease progression as an event. No trial reported sensitivity or supplementary analyses for the TTD in terms of censoring rules, or model assumptions, or reported TTD results aligned with the estimand framework or clearly specified the handling of intercurrent events.

CONCLUSIONS: Time to first deterioration remains the most frequent TTD definition in NSCLC trials but confirmed and definitive deterioration have started gaining ground. Although few studies do report more than one definition, most trials mention a single type of TTD definition and threshold. No sensitivity or supplementary analyses were reported. Analyses reported in clinical trial-related articles are not aligned with recommendations for addressing intercurrent events and missing data.