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Background: Advances in the miniaturization of sensors and other technologies provide opportunities to collect physiological and/or functional data directly from patients participating in clinical trials. The use of such technologies in children is particularly promising. Objective, quantifiable measurements made by these technologies, often on a continuous or frequent basis, may provide more robust data than the episodic reports from caregivers that are used in traditional pediatric trials. Methods: We reviewed the pros and cons of these technologies for use in a variety of pediatric diseases, including seizure and neuromuscular disorders, cardiorespiratory diseases, and metabolic disorders. Results: Correlation between sensor measurements and patient observations or traditional clinical measurements varied depending on the disease being evaluated. There was a notable dearth of reports on the use of digital health technology in pediatric patients. Given the range of sensors and measurements that can be made by DHTs, selection of the design, metrics and types of sensors best suited to disease evaluation presents challenges for adoption of these technologies in clinical trials. Conclusion: Traditional measurements of drug effects are often deficient, particularly in the evaluation of infants and young children. The opportunity to make objective, frequent measurements may increase our power to detect and quantify responses to therapy in these populations. Further research and evaluation are needed to realize the full scientific potential of remote monitoring in pediatric clinical trials. [ABSTRACT FROM AUTHOR]

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. [ABSTRACT FROM AUTHOR]

IMPORTANCE Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. OBJECTIVE TO identify the reasons that FDA marketing approval for new drugs was delayed or denied. DESIGN. SETTING. AND PARTICIPANTS A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. MAIN OUTCOMES AND MEASURES Reasons for delayed FDA approval or nonapproval of NME applications. RESULTS Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.O5%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals (61 of 80 never approved [76.3%] vs 28 of 71 eventually approved [39.4%]; difference, 36.9% [95% CI, 20.25% to 50.86%]; P < .001). CONCLUSIONS AND RELEVANCE Several potentially preventable deficiencies, including failure to select optimal drug doses and suitable study end points, accounted for significant delays in the approval of new drugs. Understanding the reasons for previous failures is helpful to improve the efficiency of clinical development for new drugs. [ABSTRACT FROM AUTHOR]

Randomized clinical trials are regarded as the gold standard for evaluating the effectiveness and safety of interventions. The US Food and Drug Administration (FDA) has made efforts to promote inclusive eligibility criteria. The objective of this study is to identify common trends in eligibility criteria and identify patterns of exclusion criteria among different diseases. The authors evaluated the inclusion and exclusion criteria of 38 pivotal clinical trials representing 38 novel drugs approved between 2014 and 2017. Additionally, the authors reviewed the demographic characteristics of participants enrolled across 38 trials. Eighty two percent of trials in our study excluded participants based on hepatic related criteria and 79% trials excluded participants based on renal related criteria and specific infectious diseases. For trials in conditions that affected both men and women, there were no exclusions based on gender and race. More than 90% of trials excluded pregnant, lactating women and women not on adequate contraception. Of the 36,644 patients enrolled in trials for which both men and women were eligible, 62% were men. The most frequent exclusion criteria were pregnancy, lactation/breastfeeding, renal and hepatic abnormalities, and specific infectious diseases. The preponderance of men in our study likely indicates that factors other than exclusion criteria affect enrollment. The lower representation of women may have been influenced by two large cardiovascular trials that included 75% men. Our study marks an important step in the ongoing efforts of the Agency to increase inclusivity in clinical trials by understanding common clinical trial eligibility criteria patterns. [ABSTRACT FROM AUTHOR]

In this Viewpoint, Janet Woodcock and CDER colleagues discuss recent FDA initiatives to investigate the adequacy of electronic health record (EHR) and patient database data for research purposes and to understand if and how real-world observational data might be analyzed in ways that mimic or can be as reliable as randomized trials. [ABSTRACT FROM AUTHOR]