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As clinical trial complexity has increased over the past decade, using electronic methods to simplify recruitment and data management have been investigated. In this study, the Optum Digital Research Network (DRN) has demonstrated the use of electronic source (eSource) data to ease subject identification, recruitment burden, and used data extracted from electronic health records (EHR) to load to an electronic data capture (EDC) system. This study utilized electronic Informed Consent, electronic patient reported outcomes (SF-12) and included three sites using 3 different EHR systems. Patients with type 2 diabetes with an HbA1c ≥ 7.0% treated with metformin monotherapy were recruited. Endpoints consisted of changes in HbA1c, medications, and quality of life measures over 12-weeks of study participation using data from the subjects' eSources listed above. The study began in June of 2020 and the last patient last visit occurred in January of 2021. Forty-eight participants were consented and enrolled. HbA1c was repeated for 33 and ePRO was obtained from all subjects at baseline and 28 at 12-week follow-up. Using eSource data eliminated transcription errors. Medication changes, healthcare encounters and lab results were identified when they occurred in standard clinical practice from the EHR systems. Minimal data transformation and normalization was required. Data for this observational trial where clinical outcomes are available using lab results, diagnoses, and encounters may be achieved via direct access to eSources. This methodology was successful and could be expanded for larger trials and will significantly reduce staff effort and exemplified clinical research as a care option., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors are direct employees of OptumInsight, the division of the company that funded the study described in this manuscript: Cynthia Senerchia, Tracy L. Ohrt, Peter N. Payne, Samantha Cheng, David Wimmer, Irene Margolin-Katz, Devin Tian, The following author is an employee of Reliant Medical Group, a part of OptumCare, separate from the division of Optum (OptumInsight) that provided funding for the study described in this manuscript: Lawrence Garber. The following authors own stock or stock options in United Health Group, the parent company of the company that funded the study (OptumInsight): Cynthia Senerchia, Tracy Ohrt, Peter Payne, Samantha Cheng., (© 2022 The Authors.)

Background & Aims: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions., Methods: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria ; the secondary endpoint was the biochemical response according to normal range criteria , defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed., Results: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria , and 11% by normal range criteria . Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p  = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p  = 0.004), although with similar ALP reduction (29.4% vs. 34%, p  = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p  = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p  = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%)., Conclusions: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC., Lay Summary: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Competing Interests: The authors have no conflicts of interest to declare related to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Author(s).)

Objective: To determine immediate performance measures for short-term, multicomponent cardiac rehabilitation (CR) in clinical routine in patients of working age, taking into account cardiovascular risk factors, physical performance, social medicine, and subjective health parameters and to explore the underlying dimensionality., Design: Prospective observational multicenter register study in 12 rehabilitation centers throughout Germany., Setting: Comprehensive 3-week CR., Participants: Patients (N=1586) ≤65 years of age (mean 53.8±7.3y, 77.1% men) in CR (May 2017-May 2018)., Interventions: Not applicable., Main Outcome Measures: Feasibility, defined by data availability for ≥85% of patients (CR admission and discharge), and modifiability based on pre-post comparison (statistical significance, with P value<.01; standardized effect size≥.35; change by ≥5% points in categorical variables). In addition, latent factors were identified using an exploratory factor analysis (EFA)., Results: Based on feasibility and modifiability criteria, smoking behavior, lifestyle change behavior, blood pressure, endurance training load, depression in Patient Health Questionnaire-9 (PHQ-9), the 5-item World Health Organization Well-Being Index (WHO-5), physical and mental health and pain scale of the indicators of rehabilitation status-24 (IRES-24), and self-assessed health prognosis proved to be suitable performance measures. As a result of the EFA, 2 solid factors were identified: (1) subjective mental health including PHQ-9, WHO-5, mental health (IRES-24), mental quality of life, and anxiety and (2) physical health including physical quality of life, physical health and pain scale of IRES-24, and self-assessed occupational prognosis. A third factor represents the blood pressure., Conclusions: We provide a small set of performance measures, that are essentially based on 3 latent factors (subjective mental health, physical health, blood pressure). These performance measures can represent immediate success of comprehensive CR and be applied easily in clinical practice., (© 2020 The Authors.)

Introduction: Amyotrophic lateral sclerosis (ALS) is an intractable and incurable neurological disease. It is a progressive disease characterized by muscle atrophy and weakness caused by selective vulnerability of upper and lower motor neurons. In disease research, it has been common to use mouse models carrying mutations in responsible genes for familial ALS as pathological models of ALS. However, there is no model that has reproduced the actual conditions of human spinal cord pathology. Thus, we developed a method of producing human spinal motor neurons using human induced pluripotent stem cells (iPSCs) and an innovative experimental technique for drug screening. As a result, ropinirole hydrochloride was eventually discovered after considering such results as its preferable transitivity in the brain and tolerability, including possible adverse reactions. Therefore, we explore the safety, tolerability and efficacy of ropinirole hydrochloride as an ALS treatment in this clinical trial., Methods: The ROPALS trial is a single-center double-blind randomized parallel group-controlled trial of the safety, tolerability, and efficacy of the ropinirole hydrochloride extended-release tablet (Requip CR) at 2- to 16-mg doses in patients with ALS. Twenty patients will be recruited for the active drug group (fifteen patients) and placebo group (five patients). All patients will be able to receive the standard ALS treatment of riluzole if not changed the dosage during this trial. The primary outcome will be safety and tolerability at 24 weeks, defined from the date of randomization. Secondary outcome will be the efficacy, including any change in the ALS Functional Rating Scale-Revised (ALSFRS-R), change in the Combined Assessment of Function and Survival (CAFS), and the composite endpoint as a sum of Z-transformed scores on various clinical items. Notably, we will perform an explorative search for a drug effect evaluation using the patient-derived iPSCs to prove this trial concept. Eligible patients will have El Escorial Possible, clinically possible and laboratory-supported, clinically probable, or clinically definite amyotrophic lateral sclerosis with disease duration less than 60 months (inclusive), an ALSFRS-R score ≥2 points on all items and age from 20 to 80 years., Conclusion: Patient recruitment began in December 2018 and the last patient is expected to complete the trial protocol in November 2020., Trial Registration: Current controlled trials UMIN000034954 and JMA-IIA00397., Protocol Version: version 1.6 (Date; 5/Apr/2019).