Association between health-related quality-of-life results, outcomes of efficacy and drug approvals: a meta-research study of randomized phase III trials in oncology.

ABSTRACT

BACKGROUND: Despite the interest from the scientific community and regulatory agencies, limited data are available on the association between health-related quality-of-life (QoL) results, outcome of efficacy and drug approvals. MATERIALS AND METHODS: We updated the previously published meta-research study of phase III clinical trials in patients with solid tumours treated with systemic treatments, published from 2012 to 2021 in 11 selected journals. For the present analysis, we focused on studies conducted in the advanced setting. The primary outcome was the association of global QoL results with study primary endpoints (EP1), overall survival (OS) and progression-free survival (PFS), while a secondary outcome was the frequency of positive global QoL results among treatments approved by regulatory agencies [European Medicines Agency (EMA)/Food and Drug Administration (FDA)]. A descriptive analysis was carried out and the association between QoL results and characteristics of studies and of publications was tested. RESULTS: Five hundred and ninety-two eligible publications were identified from 2012 to 2021. The primary endpoint was OS in 298 clinical trials (50.3%) and PFS in 304 clinical trials (51.4%). A positive result in EP1 analysis was reported in 124 trials (41.6%) with OS as EP1 and in 182 trials (59.5%) with PFS as EP1. Among studies with positive OS and PFS, global QoL results were positive in 39 (31.5%) and 45 studies (24.7%), respectively. FDA and EMA approvals were available for 143 (24.2%) and 142 studies (24%), respectively. Among these, global QoL results were positive in 55 (38.5%) and 56 studies (39.4%), respectively. QoL results were available for most drugs approved by regulatory agencies, but the proportion of approvals with positive global QoL results was not significantly increased from 2012-2016 to 2017-2021. CONCLUSIONS: Despite QoL data being available for most cancer treatments recently approved by regulatory agencies, QoL improvement has been demonstrated in a minority of studies with positive results in the primary endpoint.