Challenges and recommendations for advancing the state-of-the-science of quality of life assessment in symptom management trials.

Major findings are presented from a workshop on Quality of Life Assessment in Cancer Symptom Management Trials, sponsored by the National Cancer Institute. Data-driven research reports focused on 3 topics, 1) the rationale and utility of health-related quality of life (HRQOL) assessment, 2) conceptual models, and 3) measurement and design issues. Recommendations for including HRQOL assessment cited the potential value of: capturing additional treatment effects (eg, fatigue + depression); describing the patient experience; predicting patient prognosis; identifying potential adverse effects; observing interactions among symptoms; calculating quality adjusted survival and cost-effectiveness; and generating new hypotheses. Recommendations for developing more fully developed conceptual models focused on maintaining clear distinctions among symptoms, function, summary measures of HRQOL, and global HRQOL assessments; identifying symptom clusters; pursuing hypotheses about whether clustering is better explained as symptom-related or as patient-related (genetic predispositions); and gaining a better understanding of the dynamic and reciprocal influences of symptoms on each other. With respect to measurement and design issues, because different HRQOL measures cover different domains with various degrees of sensitivity, there is a need to select measures that are carefully tailored to the study's hypotheses. Finally, there is a growing appreciation that trials must be powered to test for effects on secondary endpoints.

Research-design issues in cancer-symptom-management trials using complementary and alternative medicine: lessons from the National Cancer Institute Community Clinical Oncology Program experience.

PURPOSE: To identify major research-design issues in proposals submitted by investigators in the Community Clinical Oncology Program (CCOP) for clinical trials of complementary and alternative medicine (CAM) for cancer-symptom management. METHODS: We conducted content analysis of all scientific reviews of concepts and protocols submitted by the CCOP to the National Cancer Institute (NCI) to identify research challenges in conducting clinical trials designed to evaluate CAM interventions for cancer-symptom management. RESULTS: Since the inception of the NCI Office of Cancer Complementary and Alternative Medicine in 1998, a total of 46 symptom-management studies using CAM interventions have been proposed by CCOP investigators, with 20 studies now in progress comprising 22% of the current total CCOP symptom-management portfolio. Proposals fell into four categories: complex natural products; nutritional therapeutics; mind-body interventions; and alternative medical systems. The most significant research-design issues arose as a consequence of the lack of preclinical data for CAM interventions and the lack of quality-control standards comparable with those used in regulating new pharmaceutical agents. CONCLUSION: Across the different types of CAM interventions, the most common problems found in proposed research designs are related to unwarranted assumptions about the consistency and standardization of CAM interventions, the need for data-based justifications for the study hypotheses, and the need to implement appropriate quality control and monitoring procedures during the course of the trial. To advance the state of the science, future research must address these critical issues if CAM interventions are to be evaluated rigorously and have a consequent impact on clinical practice and general public awareness.

Quality-of-life assessment in the symptom management trials of the National Cancer Institute-supported Community Clinical Oncology Program.

PURPOSE: To examine how quality of life (QOL) is prospectively conceptualized, defined, and measured in the symptom management clinical trials supported by the National Cancer Institute Community Clinical Oncology Program (CCOP). METHODS: All QOL research objectives, rationales, assessment instruments, symptoms treated, and types of interventions from the CCOP symptom management portfolio of clinical trials were extracted and analyzed. RESULTS: QOL assessments were proposed in 68 (52%) of the 130 total CCOP symptom management trials initiated since 1987. A total of 22 global QOL instruments were identified. Both the frequency of symptom management trials and the frequency of QOL assessment have increased significantly over time. The Functional Assessment of Cancer Therapy and Uniscale instruments were the most widely used QOL instruments, included in 55% of trials assessing QOL. The conceptual framework for QOL inclusion was limited to univariate relationships between symptom relief and global improvements in QOL. No consistent associations were found between QOL assessment and either the symptoms targeted or types of interventions. CONCLUSION: To advance the state of the science, research protocols need to provide more explicit rationales for assessing QOL in symptom management trials and for the selection of the QOL instrument(s) to be used. Conceptual frameworks that specify the hypothesized links between the specific symptom(s) being managed, interactions with other symptoms, different domains of QOL, and global QOL also need to be more precisely described. Methodologic and conceptual advances in QOL symptom management trials are critical to fulfill the promise of alleviating suffering and improving the QOL of cancer patients.