COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

OBJECTIVES: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy. METHODS: Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database. RESULTS: In the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22-0.69; P=0.001). No new safety signals were identified in the RCT. CONCLUSIONS: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC.

Primary care micro-teams: an international systematic review of patient and healthcare professional perspectives.

BACKGROUND: International trends have shifted to creating large general practices. There is an assumption that interdisciplinary teams will increase patient accessibility and provide more cost-effective, efficient services. Micro-teams have been proposed to mitigate for some potential challenges of practice expansion, including continuity of care. AIM: To review available literature and examine how micro-teams are described, and identify opportunities and limitations for patients and practice staff. DESIGN AND SETTING: This was an international systematic review of studies published in English. METHOD: Databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus) and grey literature were searched. Studies were included if they provided evidence about implementation of primary care micro-teams. Framework analysis was used to synthesise identified literature. The research team included a public contributor co-applicant. The authors conducted stakeholder discussions with those with and without experience of micro-team implementation. RESULTS: Of the 462 studies identified, 24 documents met the inclusion criteria. Most included empirical data from healthcare professionals, describing micro-team implementation. Results included characteristics of the literature; micro-team description; range of ways micro-teams have been implemented; reported outcomes; and experiences of patients and staff. CONCLUSION: The organisation of primary care has potential impact on the nature and quality of patient care, safety, and outcomes. This review contributes to current debate about care delivery and how this can impact on the experiences and outcomes of patients and staff. This analysis identifies several key opportunities and challenges for future research, policy, and practice.

Primary care micro-teams: a protocol for an international systematic review to describe and examine the opportunities and challenges of implementation for patients and healthcare professionals.

INTRODUCTION: There has been a recent trend towards creating larger primary care practices with the assumption that interdisciplinary teams can deliver improved and more cost-effective services to patients with better accessibility. Micro-teams have been proposed to mitigate some of the potential challenges with practice expansion, including continuity of care. We aim to review the available literature to improve understanding of how micro-teams are described and the opportunities which primary care micro-teams can provide for practice staff and patients and limitations to their introduction and implementation. Our review asks: how is micro-team implementation described? What are the experiences of healthcare professionals and patients concerning micro-teams in primary care? What are the reported implications of micro-teams for patient care? METHODS AND ANALYSIS: CINAHL, Cochrane Library, Embase, MEDLINE and Scopus will be searched for studies in English. Grey literature will be sourced from Google Scholar, government websites, CCG websites, general practice directives and strategies with advice from stakeholders. Included studies will give evidence regarding the implementation of micro-teams. Data will be synthesised using framework analysis. We will use iterative stakeholder and public and patient participation to embed the perspectives of those whom micro-teams could impact. Included studies will be quality assessed using the Mixed Methods Appraisal Tool. The quality assessment will not be used to exclude any evidence but rather to develop a narrative discussion evaluating included literature. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this systematic review as there will only be a secondary analysis of data already available in scientific databases and the grey literature. This protocol has been submitted for registration to be made available on a review database (PROSPERO). Findings will be disseminated widely through peer-reviewed publication and in various media, for example, conferences, congresses or symposia. PROSPERO REGISTRATION NUMBER: CRD42021225367.