OBJECTIVES: TTD is considered a common longitudinal analysis for HRQoL in oncology trials. Different definitions can be used depending on the disease stage, expected impact of the disease, and treatment received. However, varying definitions across clinical trials may preclude comparison of results and lead to an underutilization of HRQoL data. This is a targeted literature review of the TTD definitions used in NSCLC trials.

METHODS: A search in clinicaltrials.gov was performed with the following terms: “NSCLC, quality of life” and applying the filter for completed studies. Only studies with completion date from January 2013 onwards or blank were selected for review. Study results were searched on clinicaltrials.gov, PubMed, Annals of Oncology and websites of ASCO, ESMO and NICE. The disease stage, instruments used, TTD definition, threshold for deterioration and censoring rules were abstracted and summarised.

RESULTS: We identified 244 studies, of which 85 were included in the review. 15 reported TTD analyses: 9 provided the exact definition and 6 reported results, but did not specify the exact definition applied. The instruments used were: EORTC QLQ-C30/LC13 (n=7), LCSS (n=5) and FACT-L (n=3). Among those studies reporting at least part of the definition used, 8 used time to first deterioration and 5 used different composite endpoints of first deterioration of either one or more symptoms, death or initiation of chemotherapy. Only 1 study required confirmation of deterioration at a subsequent visit. Definitive deterioration was not identified in any study. Five studies described the censoring rules for TTD. Reported thresholds were 10 for QLQ-C30, 5 for QLQ-LC13, half SD at baseline for LCSS and none for FACT-L.

CONCLUSIONS: TTD provides meaningful information to clinicians. Its elements, i.e. events, censoring and threshold, should be carefully selected. While longitudinally-collected HRQoL is considered a major endpoint in oncology, TTD analyses are still underreported and unstandardized in NSCLC.