Some unresolved issues for the study of fatigue: the way forward.

This section of the supplement “Fatigue: A New Frontier” will discuss 3 issues that have significant import for elucidating mechanisms by which fatigue occurs and its evaluation and treatment. These issues are clearly not the only ones that are important for future research or clinical practice, but they are the most prevalent issues raised in the articles of this supplement. They present significant challenges in both research and clinical arenas and offer substantial research opportunity. There exists a body of published data that leave a number of unresolved key issues. These include: 1) What are our best metrics for measuring fatigue? 2) Do the constructs of peripheral and central fatigue advance our understanding of fatigue syndromes or create arbitrary limitations? 3) Will a better understanding of the interactions among immunoregulation and metabolic control of energy production and utilization (and performance and perception) help us derive a comprehensive approach to the management of fatigue? What are the Best Metrics for Measuring Fatigue? Many of the sections of this supplement address the need for valid and reliable instruments for measuring fatigue. The authors identify instruments that were specifically developed for use in some of the disease entities they discuss. For example, the Fatigue Severity Scale has been used to assess fatigue in rheumatic diseases and multiple sclerosis. Whereas in assessing cancer-related fatigue, other self-report instruments have been used, including the Functional Assessment of Cancer Therapy-Fatigue, Cancer Fatigue Scale, and Brief Fatigue Inventory, among others. Self-reports are necessary for assessing fatigue, but many suggest that they are not sufficient. The trend is toward using instruments that are coupled with objective findings. For example, in cancer-related fatigue and the neurological conditions, studies have included measures of neuromuscular fatigue. As discussed in this theme issue, there seems to be a shift in thinking about what is most important in measuring fatigue in the elderly. In particular, the concept of fatigability, which links fatigue with function and thereby assesses the impact fatigue may have on independence, has gained momentum as the measurement of choice. Fatigue measures in the affective/fatigue or pain/fatigue overlap syndromes, such as chronic fatigue syndrome and fibromyalgia (FM), remain reliant on self-reports of symptoms, mood, and behavior. Most authors contributing to this special issue indicate that one of the more significant problems facing clinicians and researchers studying and treating fatigue is reaching agreement on which measures to use for evaluation and treatment outcomes. There has not been consensus on whether fatigue measures should or must include objective measures, or whether they need to be disease specific. There does not seem to be consensus on what the essential components of a fatigue measure need be and whether this would be true for all or most chronic medical conditions, including those that may have significant psychoaffective and biopsychosocial components. This is an opportune time to promote a Consensus Conference designed to explore issues such as how to measure fatigue and what should be included in these measures. Such a conference would also introduce the use of theories and approaches to computer technologies such as item response theory and computerized-adapted training to help assure validity and efficiency in the choice of relevant metrics. One such approach, patient reported outcomes medical information system (PROMIS), has been instrumen