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.