The Added Value of Analyzing Pooled Health-Related Quality of Life Data: A Review of the EORTC PROBE Initiative

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. METHODS: The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. RESULTS: Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomiting (P = .01), nausea (P < .001), and constipation (P = .01). Greater understanding of the association between symptom and/or functioning scales was developed by identifying physical, psychological, and gastrointestinal clusters. Additionally, minimally important differences in interpreting HRQOL changes for improvement and deterioration were found to vary across different patient populations and disease stages. Finally, HRQOL scores are statistically significantly affected by deviations from the intended time point at which the questionnaire is completed. CONCLUSIONS: The use of existing pooled data shows that it is possible to learn about general aspects of cancer HRQOL and methodology. Our work shows that setting up international pooled datasets holds great promise for understanding patients' unmet psychosocial needs and calls for additional empirical investigation to improve clinical care and understand cancer through retrospective HRQOL analyses

The effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients.

Cancer incidence increases exponentially with advancing age, cancer patients live longer than in the past, and many new treatments focus on stabilizing disease and HRQOL. The objective of this study is to examine how cancer affects patients' HRQOL and whether their HRQOL is age-dependent.Data from 25 EORTC randomized controlled trials was pooled. EORTC QLQ-C30 mean scores for the cancer cohort and five general population cohorts were compared to assess the impact of cancer on patients' HRQOL. Within the cancer cohort, multiple linear regressions (two-sided level P-value = 0.05 adjusted for multiple testing.) were used to investigate the association between age and HRQOL, adjusted for gender, WHO performance status (PS), distant metastasis and stratified by cancer site. A difference of 10 points on the 0-100 scale was considered clinically important.Cancer patients generally have worse HRQOL compared to the general population, but the specific HRQOL domains impaired vary with age. When comparing the cancer versus the general population, young cancer patients had worse financial problems, social and role functioning, while the older cancer groups had more appetite loss. Within the cancer cohort, HRQOL was worse with increasing age for physical functioning and constipation, and better with increasing age for social functioning, insomnia and financial problems (all p < 0.05).HRQOL is impaired in cancer patients compared to the general population, but the impact on specific HRQOL domains varies by age. Within the cancer population, some HRQOL components improve with age while others deteriorate. Optimal care for older cancer patients should target HRQOL domains most relevant to this population

Impact of neurocognitive deficits on patient–proxy agreement regarding health-related quality of life in low-grade glioma patients

Purpose: Clinical trials in glioma patients with neurocognitive deficits face challenges due to lacking or unreliable patient self-reports on their health-related quality of life (HRQOL). Patient–proxy data could help solve this issue. We determined whether patient–proxy concordance levels were affected by patients’ neurocognitive functioning. Methods: Patient and patient-by-proxy HRQOL ratings were assessed via SF-36 and EORTC QLQ-BN20, respectively, in 246 patients. Data on neurocognitive functioning were collected on a subgroup of 195 patients. Patient–proxy agreement was measured using the Bland–Altman limit of agreement, the mean difference, the concordance correlation coefficient (CCC), and the percentage difference (PD, ±0, 5, or 10 points). We defined patients to be cognitively impaired (n = 66) or cognitively intact (n = 129) based on their neurocognitive performance. Results: Patients rated their physical function and general health to be better than their proxies did, while at the same time, patients reported more visual disorders, communication deficits, itchy skin, and problems with bladder control. The cognitively impaired subgroup reported poorer physical functioning, more visual disorders, headaches, itchy skin, and issues with bladder control. In the cognitively intact group, no statistical significant differences were observed between patients and proxies. Not surprisingly, Bland–Altman plots revealed a high agreement between the patient and patient-by-proxy rating in all HRQOL domains ranging from 95 to 99 %. The CCC was fairly high in all HRQOL domains (0.37–0.80), and the percentage of perfect agreement (PD ± 0) ranged from 8.5 to 76.8 %. In the cognitively impaired patients, the mean difference between patients and proxies was overall larger, and accordingly, agreement based on Bland–Altman plots was lower. Conclusions: The level of agreement between patient and patient-by-proxy ratings of low-grade glioma patients’ HRQOL is generally high. However, patient–proxy agreement is lower in patients with neurocognitive deficits than in patients without neurocognitive deficits

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trial

A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites

The objective of this study was to examine the prognostic value of baseline health-related quality of life (HRQOL) for survival with regard to different cancer sites using 1 standardized and validated patient self-assessment tool. In total, 11 different cancer sites pooled from 30 European Organization for Research and Treatment of Cancer (EORTC) randomized controlled trials were selected for this study. For each cancer site, univariate and multivariate Cox proportional hazards modeling was used to assess the prognostic value (P < .05) of 15 HRQOL parameters using the EORTC Core Quality of Life Questionnaire (QLQ-C30). Models were adjusted for age, sex, and World Health Organization performance status and were stratified by distant metastasis. In total, 7417 patients completed the EORTC QLQ-C30 before randomization. In brain cancer, cognitive functioning was predictive for survival; in breast cancer, physical functioning, emotional functioning, global health status, and nausea and vomiting were predictive for survival; in colorectal cancer, physical functioning, nausea and vomiting, pain, and appetite loss were predictive for survival; in esophageal cancer, physical functioning and social functioning were predictive for survival; in head and neck cancer, emotional functioning, nausea and vomiting, and dyspnea were predictive for survival; in lung cancer, physical functioning and pain were predictive for survival; in melanoma, physical functioning was predictive for survival; in ovarian cancer, nausea and vomiting were predictive for survival; in pancreatic cancer, global health status was predictive for survival; in prostate cancer, role functioning and appetite loss were predictive for survival; and, in testis cancer, role functioning was predictive for survival. The current results demonstrated that, for each cancer site, at least 1 HRQOL domain provided prognostic information that was additive over and above clinical and sociodemographic variable