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.
Joly, F. and J. Vardy, M. Pintilie, I. F. Tannock
Disease Category: Cancer
Disease Name: N/A
Age Range: 18 - 100
Sex: Either
Nature of Intervention: Not specified
- None
- Recommendations made
- Systematic review of outcome measures/measurement instruments
- Systematic review of outcomes measured in trials
- Systematic review
In February 2004, a literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (Cochrane Library 2004, First quarter) using the following key words from the title and/or the abstract: health-related quality of life AND advanced cancer, and/or palliation, symptoms and/or metastatic cancer. The search strategy was restricted to ‘randomized controlled trials’ where the subjects were greater than 18 years old and to publications in English dating from January 1994 to January 2004.
We reviewed randomized phase III trials that assessed self-reported QoL or symptom control as a primary or secondary outcome measure in patients with advanced cancer. We were interested in larger trials and so set an arbitrary lower limit on sample size of 150 patients. Trials that used only physician-reported questionnaires were excluded, as were studies that did not evaluate a palliative strategy or treatment.