Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess the efficacy of a drug. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts: symptomatic adverse events, physical function, and disease-related symptoms, which are key contributors to the effect of a therapy on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials.
Objective. Diverse neurologic syndromes have been described in association with tumor necrosis factor ␣ (TNF␣) antagonist therapy for inflammatory arthritides and Crohn's disease. The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNF␣ antagonist therapy.Methods. The postmarketing database of the US Food and Drug Administration (FDA) was searched, following our experience with a patient with rheumatoid arthritis in whom the Miller Fisher syndrome variant of the Guillain-Barré syndrome developed while he was receiving infliximab therapy.Results. Our index patient had a neurologic illness defined initially by ataxia and dysarthria, which fluctuated in relation to each subsequent infliximab infusion and, after 6 months, culminated in areflexic flaccid quadriplegia. In addition, 15 patients in whom Guillain-Barré syndrome developed following TNF␣ antagonist therapy were identified from the FDA database. Guillain-Barré syndrome developed following infliximab therapy in 9 patients, following etanercept therapy in 5 patients, and following adalimumab therapy in 1 patient. Among the 13 patients for whom followup data were available, 1 patient experienced no resolution, 9 patients had partial resolution, and 3 patients had complete resolution of Guillain-Barré syndrome following therapy.Conclusion. An association of Guillain-Barré syndrome with TNF␣ antagonist therapy is supported by the worsening of neurologic symptoms that occurred in our index patient following each infusion of infliximab, and by the temporal association of this syndrome with TNF␣ antagonist therapy in 15 other patients. An acute or subacute demyelinating polyneuropathy should be considered a potential adverse effect of TNF␣ antagonist therapy.
The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane‐bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual‐color fluorescence microscopy co‐localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK‐positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up‐regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF‐α or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5‐fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell‐cell communication.
Background: The use of mobile devices in clinical research has advanced substantially in recent years due to the rapid pace of technology development. With an overall aim of informing the future use of mobile devices in interventional clinical research to measure primary outcomes, we conducted a systematic review of the use of and clinical outcomes measured by mobile devices (mobile outcomes) in observational and interventional clinical research. Method: We conducted a PubMed search using a range of search terms to retrieve peer-reviewed articles on clinical research published between January 2010 and May 2016 in which mobile devices were used to measure study outcomes. We screened each publication for specific inclusion and exclusion criteria. We then identified and qualitatively summarized the use of mobile outcome assessments in clinical research, including the type and design of the study, therapeutic focus, type of mobile device(s) used, and specific mobile outcomes reported. Results: The search retrieved 2,530 potential articles of interest. After screening, 88 publications remained. Twenty-five percent of the publications (n = 22) described mobile outcomes used in interventional research, and the rest (n = 66) described observational clinical research. Thirteen therapeutic areas were represented. Five categories of mobile devices were identified: (1) inertial sensors, (2) biosensors, (3) pressure sensors and walkways, (4) medication adherence monitors, and (5) location monitors; inertial sensors/accelerometers were most common (reported in 86% of the publications). Among the variety of mobile outcomes, various assessments of physical activity were most common (reported in 74% of the publications). Other mobile outcomes included assessments of sleep, mobility, and pill adherence, as well as biomarkers assessed using a mobile device, including cardiac measures, glucose, gastric reflux, respiratory measures, and intensity of head-related injury. Conclusion: Mobile devices are being widely used in clinical research to assess outcomes, although their use in interventional research to assess therapeutic effectiveness is limited. For mobile devices to be used more frequently in pivotal interventional research – such as trials informing regulatory decision-making – more focus should be placed on: (1) consolidating the evidence supporting the clinical meaningfulness of specific mobile outcomes, and (2) standardizing the use of mobile devices in clinical research to measure specific mobile outcomes (e.g., data capture frequencies, placement of device). To that aim, this manuscript offers a broad overview of the various mobile outcome assessments currently used in observational and interventional research, and categorizes and consolidates this information for researchers interested in using mobile devices to assess outcomes in interventional research.
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