Quality of life and/or symptom control in randomized clinical trials for patients with advanced cancer.

BACKGROUND Measures reflecting quality of life (QoL) or symptom control should be included as major endpoints in most phase III trials for patients with advanced cancer. Here we review the use of such endpoints. METHODS We evaluated methodological aspects relating to QoL or symptom control in randomized controlled trials (RCTs) that included >or=150 patients, published from 1994 to 2004, using a 10-point checklist. RESULTS Of 112 RCTs that met our criteria, few were rated as high quality: 22% defined QoL or symptom control as a primary endpoint; 19% established an a priori hypothesis relevant to palliation and 21% defined minimal differences in QoL or symptom scores that were clinically meaningful. Most trials (81%) analyzed differences between mean or median scores across groups and only 21% defined the proportion of individual patients who met criteria for palliative response. Only 15% of the studies met more than 5/10 criteria from our checklist. There was improvement over time in methodology and reporting. CONCLUSIONS Current standards for analyzing QoL and symptom control in RCTs are poor. Definition of a palliative endpoint, with an a priori hypothesis, is essential; defining the proportion of patients with palliative response is preferred. The proposed checklist could raise standards of reporting in future RCTs.