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Patient-Reported Outcomes Assessment in Cancer Trials: Evaluating and Enhancing the Payoff to Decision Making

National Cancer Institute, Bethesda, MD

Patricia A. Ganz

UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, CA

Joseph Lipscomb

Emory University, Atlanta, GA

Bryce B. Reeve

National Cancer Institute, Bethesda, MD

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 Group¹ and by the US Food and Drug Administration's recent guidance for the use of PROs in product labeling.²

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.³ 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).⁴ 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.⁵

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.⁶ 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.⁷

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 "Patient-Reported 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 cancer trials sponsored by NCI, industry, and clinical trials groups abroad, with a focus ultimately on Canada and Europe. Emerging from the committee's deliberations was a conference agenda organized around evidence-driven presentations and discussions of progress and challenges to date in the use of PROs in phase II and phase III treatment trials and in symptom management trials. (While screening and prevention trials and phase IV [post–product-approval] trials are potentially important arenas for PRO application, they were deemed less central at this point to the NCI SxQOL mission, though ripe areas for future investigation.) The conference concluded with a roundtable discussion to summarize lessons learned from the 2 days of presentations and discussions, with a focus on ways to improve the scientific soundness, feasibility, and policy relevance of PROs. A recurring theme throughout the PROACT conference was the importance of capitalizing on existing research and experience to assist the NCI's CTWG in improving the design, review, funding, and use of PROs in NCI-supported cancer clinical trials. The PROACT Scientific Program Committee, conference agenda, and presentations may be viewed online at outcomes.cancer.gov/publications/workshops/proact/.

The 13 articles contained in this Review Issue of the Journal of Clinical Oncology provide a comprehensive summary of the output from the PROACT conference. Taken together, the articles reflect a diversity of viewpoints, but also a shared sense of purpose regarding the importance of measuring cancer outcomes from the patient's perspective. Some articles provide descriptive information on the clinical trial infrastructure in NCI-supported, as well as US pharmaceutical industry–supported trials that use PROs. Others elucidate the issues and opportunities for improving the planning, design, methods, and implementation of PROs in cancer clinical trials at all phases of development. Advancements in measuring PROs are also described. Additional perspective on PROs is provided by representatives from the US Food and Drug Administration, the pharmaceutical industry, and from clinical trial researchers from Canada and Europe. The issue ends with an article that synthesizes the key themes that emerged across all the articles, and includes recommendations from conference attendees for improving future prioritization, administration, and conduct of NCI-supported clinical trials that use PROs.

Current efforts to incorporate PROs into cancer trials will need to draw from past approaches while developing new strategies. Innovative cancer therapies and treatments hold promise for extending the length of life of individuals suffering from cancer. However, many of these therapies also may have sequellae that affect the health-related quality of life of patients with cancer. Our hope is that the articles contained in this issue will promote dialog and stimulate efforts that are ultimately effective in incorporating the patient's perspective in understanding the potential for new cancer therapies and technologies to extend the quantity and quality of life among individuals with cancer.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

AUTHOR CONTRIBUTIONS

Manuscript writing: Steven B. Clauser, Patricia A. Ganz, Joseph Lipscomb, Bryce B. Reeve

REFERENCES

1. Lipscomb J, Gotay CC, Snyder C Outcomes Assessment in Cancer: Measures, Methods, and Applications. New York, NY, Cambridge University Press, 2005

2. US Food and Drug Administration: Patient-reported outcome measures: Use in medical product development to support labeling claims. Accessed August 1, 2007. Available at: http://www.fda.gov/cder/guidance/5460dft.pdf

3. National Cancer Institute: The Nation's Investment in Cancer Research: A plan and Budget Proposal for Fiscal Year 2008. NIH Publication No. 06-6090. Available at: http://plan.cancer.gov/plan_overview.shtml

4. Garcia SF, Cella D, Clauser S, et al: Enhancing patient-reported outcomes assessment in cancer clinical trials: The PROMIS initiative. J Clin Oncol 25:5106-5112, 2007[Abstract/Free Full Text]

5. National Cancer Institute, Bio-Informatics Grid (caBIG)—Overview. Accessed August 15, 2007. Available at https://cabig.nci.nih.gov/overview

6. National Cancer Institute: Restructuring the National Cancer Clinical Trials Enterprise: Report of the Clinical Trials Working Group of the National Cancer Advisory Board. June 2005. Accessed August 15, 2007. Available at http://integratedtrials.nci.nih.gov/ict/CTWG_report_June2005.pdf

7. Minasian LM, O'Mara AM, Reeve BB, et al: Health-related quality of life and symptom management research sponsored by the National Cancer Institute. J Clin Oncol 25:5128-5132, 2007[Abstract/Free Full Text]

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