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

INTRODUCTION: 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 patients with PBC 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 analysis hazard ratio [HR] = 1.01, 95% confidence interval = 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 and as-treated analyses shifted the HR to favor OCA. In the EC (n = 1,051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR = 0.39; 95% confidence interval = 0.22-0.69; P = 0.001). No new safety signals were identified in the RCT. DISCUSSION: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the intent-to-treat 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.

Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls.

BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Factors Affecting COVID-19 Testing Behaviours Among the Population in South Western Nigeria.

Objectives: The objective of this study was to assess the factors affecting testing behaviours amongst the population in Ondo and Lagos States. Methods: A cross-sectional study involving 704 individuals who were considered eligible for COVID-19 testing in 4 local governments in Lagos (307) and Ondo (397) states in Nigeria, was conducted from April-June 2021. Respondents were selected using simple random sampling. A close-ended questionnaire was administered using a digital survey platform known as SurveyCTO. Data were analyzed using R 4.1.0. Results: In Lagos state, 52.4% were females, 47.2% were males while in Ondo, 55.2% were females, 44.6% were male. Chi-square tests of association revealed that socio demographic factors significantly associated with testing patterns was education level in Lagos, and none in Ondo. Testing behavior associated with testing patterns included awareness of nearby COVID-19 testing centers, internet access, knowledge of preexisting conditions and having another member of the family testing positive at 5% significance level. Conclusion: Knowledge of pre-existing conditions, knowledge of COVID-19 symptoms, and knowing where to go when having symptoms were significantly associated with testing and willingness to test.

The use of DIY (Do it yourself) sampling and telemonitoring model for COVID-19 qPCR testing scale up.

The first case of COVID-19 in Nigeria was recorded on February 27, 2020, being an imported case by an Italian expatriate, to the country. Since then, there has been steady increase in the number of cases. However, the number of cases in Nigeria is low in comparison to cases reported by other countries with similar large populations, despite the poor health system prevailing in the country. This has been mainly attributed to the low testing capacity in Nigeria among other factors. Therefore, there is a need for innovative ways to increase the number of persons testing for COVID-19. The aim of the study was to pilot a nasopharyngeal swab self-sample collection model that would help increase COVID-19 testing while ensuring minimal person-to-person contact being experienced at the testing center. 216 participants took part in this study which was carried out at the Nigerian Institute of Medical Research between June and July 2020. Amongst the 216 participants, 174 tested negatives for both self-collected samples and samples collected by Professionals, 30 tested positive for both arms, with discrepancies occurring in 6 samples where the self-collected samples were positive while the ones collected by the professionals were negative. The same occurred in another set of 6 samples with the self-collected samples being negative and the professional-collected sample coming out positive, with a sensitivity of 83.3% and a specificity of 96.7%. The results of the interrater analysis are Kappa = 0.800 (95% CI, 0.690 to 0.910) which implies an outstanding agreement between the two COVID-19 sampling methods. Furthermore, since p< 0.001 Kappa (k) coefficient is statistically different from zero, our findings have shown that self-collected samples can be reliable in the diagnosis of COVID-19.