Ann M. O'Mara

Recommended Patient-Reported Core Set of Symptoms to Measure in Adult Cancer Treatment Trials

BACKGROUND The National Cancer Institutes Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). METHODS We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001-2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. RESULTS We recommend that a core set of 12 symptoms--specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea--be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. CONCLUSIONS This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.

Patient-Reported Outcomes Assessment in Cancer Trials: Taking Stock, Moving Forward

To evaluate and improve the use of cancer trial end points that reflect the patients own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations.

Prevalence and characteristics of moderate to severe fatigue: A multicenter study in cancer patients and survivors

The effective management of fatigue in patients with cancer requires a clear delineation of what constitutes nontrivial fatigue. The authors defined numeric cutpoints for fatigue severity based on functional interference and described the prevalence and characteristics of fatigue in patients with cancer and survivors.

The symptom burden of cancer: Evidence for a core set of cancer-related and treatment-related symptoms from the Eastern Cooperative Oncology Group Symptom Outcomes and Practice Patterns study

A set of common cancer‐related and treatment‐related symptoms has been proposed for quality of care assessment and clinical research. Using data from a large, multicenter, prospective study, the authors assessed the effects of disease site and stage on the percentages of patients rating these proposed symptoms as moderate to severe.

ASCPRO Recommendations for the Assessment of Fatigue as an Outcome in Clinical Trials

CONTEXT Development of pharmacological and behavioral interventions for cancer-related fatigue (CRF) requires adequate measures of this symptom. A guidance document from the Food and Drug Administration offers criteria for the formulation and evaluation of patient-reported outcome measures used in clinical trials to support drug or device labeling claims. METHODS An independent working group, ASCPRO (Assessing Symptoms of Cancer Using Patient-Reported Outcomes), has begun developing recommendations for the measurement of symptoms in oncology clinical trials. The recommendations of the Fatigue Task Force for measurement of CRF are presented here. RESULTS There was consensus that CRF could be measured effectively in clinical trials as the sensation of fatigue or tiredness, impact of fatigue/tiredness on usual functioning, or as both sensation and impact. The ASCPRO Fatigue Task Force constructed a definition and conceptual model to guide the measurement of CRF. ASCPRO recommendations do not endorse a specific fatigue measure but clarify how to evaluate and implement fatigue assessments in clinical studies. The selection of a CRF measure should be tailored to the goals of the research. Measurement issues related to various research environments were also discussed. CONCLUSIONS There exist in the literature good measures of CRF for clinical trials, with strong evidence of clarity and comprehensibility to patients, content and construct validity, reliability, and sensitivity to change in conditions in which one would expect them to change (assay sensitivity), and sufficient evidence to establish guides for interpreting changes in scores. Direction for future research is discussed.

Recommendations for High-Priority Research on Cancer-Related Fatigue in Children and Adults

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current case definition to reflect more rigorous criteria, adopting the Patient Reported Outcomes Measurement Information System fatigue scales as standard measures of CRF, and linking legacy measures to the scales. With regard to the biology of CRF, the group identified the need for longitudinal research to examine biobehavioral mechanisms underlying CRF and testing mechanistic hypotheses within the context of intervention research. To address clinical trial issues, recommendations included using only placebo-controlled trial designs. setting eligibility to minimize sample heterogeneity or enable subgroup analysis, establishing a CRF severity threshold for participation in clinical trials, conducting dissemination trials of efficacious interventions (such as exercise), and combining nonpharmacologic and pharmacologic interventions to exploit the potential synergy between these approaches. Accomplishing these goals has the potential to advance the science of CRF and improve the clinical management of this troubling symptom.

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.

Translating research into evidence-based practice: the National Cancer Institute Community Clinical Oncology Program.

The recent rapid acceleration of basic science is reshaping both our clinical research system and our healthcare delivery system. The pace and growing volume of medical discoveries are yielding exciting new opportunities, yet we continue to face old challenges to maintain research progress and effectively translate research into practice. The National Institutes of Health and individual government programs increasingly are emphasizing research agendas that involve evidence development, comparative‐effectiveness research among heterogeneous populations, translational research, and accelerating the translation of research into evidence‐based practice as well as building successful research networks to support these efforts. For more than 25 years, the National Cancer Institute Community Clinical Oncology Program has successfully extended research into the community and facilitated the translation of research into evidence‐based practice. By describing its keys to success, this article provides practical guidance to cancer‐focused, provider‐based research networks as well as those in other disciplines. Cancer 2010.

Caring for caregivers and patients: Research and clinical priorities for informal cancer caregiving.

Informal/family caregivers are a fundamental source of care for cancer patients in the United States, yet the population of caregivers and their tasks, psychosocial needs, and health outcomes are not well understood. Changes in the nature of cancer care and its delivery, along with the growing population of survivors and their caregivers, warrant increased attention to the roles and demands of caregiving. This article reviews current evidence presented at a 2‐day meeting examining the state of the science of informal cancer caregiving that was convened by the National Cancer Institute and the National Institute of Nursing Research. The meeting sought to define who is an informal cancer caregiver, summarize the state of the science in informal cancer caregiving, and describe both the kinds of interventions developed to address caregiving challenges and the various outcomes used to evaluate their impact. This article offers recommendations for moving science forward in 4 areas: 1) improving the estimation of the prevalence and burden of informal cancer caregiving; 2) advancing the development of interventions designed to improve outcomes for cancer patients, caregivers, and patient‐caregiver dyads; 3) generating and testing strategies for integrating caregivers into formal health care settings; and 4) promoting the use of technology to support informal cancer caregivers. Cancer 2016;122:1987–95.

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.