Associations between safety, tolerability, and toxicity and the reporting of health-related quality of life in phase III randomized trials in common solid tumors

Abstract

Background: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health-related quality of life (HRQoL) is a direct measure of patient benefit, but is under-reported. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors. Methods: We searched ClinicalTrials.gov to identify phase III RCTs evaluating new drugs in adults with advanced cancers that completed accrual between January 2005 and October 2016. Data on HRQoL, safety, and tolerability comprising treatment-related death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs) were extracted. Associations between these measures and reporting of HRQoL data were explored using logistic regression. Results: Of 377 phase III RCTs identified initially, 143 studies were analysed and comprised 55% positive trials and 90% industry sponsored trials. HRQoL was listed as an endpoint in 59% trials; and of these, only 65% reported HRQoL data. There were higher odds of reporting HRQoL data for positive trials (OR 2.05, P =.04) and trials published in journals with higher impact factor (OR 1.35, P =.01). Reporting of HRQoL was not associated with treatment-related death (OR 1.25, P =.40) or treatment discontinuation (OR 1.12, P =.61), but was positively associated with dyspnea and dermatological adverse events. Conclusions: HRQoL is reported in only two-thirds of RCTs that describe collecting such data. Reporting of HRQoL is associated with positive trial outcome and higher journal impact factor, but not associated with overall safety and tolerability of anti-cancer drugs.