Patient-reported outcomes assessment in cancer trials: evaluating and enhancing the payoff to decision making.

In recent years, there has been a growing interest in incorporating patients’ perspectives when measuring and interpreting the clinical benefit of cancer therapies. Patient-reported outcomes (PROs) are used in a variety of cancer clinical trials. These studies range from using PROs to better understand the burden of cancer and the adverse effects of cancer therapy (such as pain), to studies that use PROs as the primary end point of the clinical trial, such as reducing symptoms like nausea or fatigue that can be caused by certain cancer therapies. The evolution of PROs in cancer trials has been recently documented by the National Cancer Institute (NCI)–supported Cancer Outcomes Measurement Working Group and by the US Food and Drug Administration’s recent guidance for the use of PROs in product labeling. PRO research also has been recognized as an important element in the NCI strategic planning process. A major NCI goal is to support research that enhances our understanding of the burden of disease among patients with cancer and cancer survivors, and reduces the sequellae of cancer throughout the continuum of care. NCI has taken an important role in developing new ways to measure patient-reported symptoms such as pain and fatigue, and aspects of health-related quality of life across a wide range of cancers and other diseases, through the Patient Reported Outcomes Measurement Information System (PROMIS). As a National Institutes of Health Roadmap initiative, PROMIS will provide clinical research communities with a reliable, valid, and standardized approach to capture these clinically relevant, but subjective and difficult-to-measure outcomes in clinical trials. Standardization of these data will provide additional benefits to the cancer clinical trial enterprise because it will eventually facilitate their incorporation into the cancer bioinformatics grid (ca-BIG), thereby making PROs available to all researchers who participate in and use the grid to support correlative research studies in connection with clinical trials. Through the NCI Clinical Trials Working Group (CTWG), NCI also has undertaken a major reassessment of the design, review, funding, and implementation of cancer clinical treatment trials and symptom management trials. Among the many recommendations contained in the CTWG report are ones to establish a new funding mechanism and prioritization process for supporting correlative science and quality-of-life studies using PROs, that can be initiated in association with clinical trials. As part of the CTWG process, NCI recently created a Symptom Management and Health-Related Quality of Life (SxQOL) Steering Committee to prioritize and review studies that include PROs as primary end points in symptom management clinical trials, and PROs as secondary end points in phase III Cooperative Group cancer treatment trials sponsored by the NCI. In addition, the SxQOL committee will provide guidance on how to improve the utility of PROs in cancer treatment trials and in symptom management trials. Although PRO data have potential utility for a variety of analyses in cancer clinical trials, the issues surrounding their appropriate and effective application are complex. In September 2006, the NCI convened a 2-day conference entitled “PatientReported Outcomes Assessment in Cancer Trials (PROACT): Evaluating and Enhancing the Payoff to Decision-Making.” This conference was cosponsored by the American Cancer Society and represented a collaborative effort among the leadership from all major NCI extramural divisions involved with clinical trials—the Division of Cancer Treatment and Diagnosis, the Division of Cancer Prevention, and the Division of Cancer Control and Population Sciences. The goal of the PROACT conference was to bring together scientists working in this area to inform NCI and the broader cancer research and policy community on how the NCI clinical trial infrastructure is currently organized to support PRO research in clinical trials, and to identify the issues and lessons learned from the experiences of NCI-sponsored cooperative groups and Community Cancer Oncology Programs; other national and international researchers; and US pharmaceutical industry experts in using PROs in phase II and III cancer treatment trials, as well as in symptom management trials. Before the conference, NCI charged a multidisciplinary Scientific Program Committee of internationally recognized experts to identify key determinants of the successful application of PROs in JOURNAL OF CLINICAL ONCOLOGY O V E R V I E W VOLUME 25 NUMBER 32 NOVEMBER 1