Use of record linkage to evaluate treatment outcomes and trial eligibility in a 1 real-world metastatic prostate cancer population in Scotland

Purpose: New treatments are introduced into standard care based on clinical trial results. However, it is not clear if these benefits are reflected in the broader population. This study analysed the clinical outcomes of patients with metastatic castration-resistant prostate cancer, treated with abiraterone and enzalutamide, within the Scottish National Health Service. Methods: Retrospective cohort study using record linkage of routinely collected healthcare data (study period: February 2012 to February 2017). Overall survival (OS) was analysed using Kaplan-Meier methods and Cox Proportional Hazard models; a subgroup analysis comprised potentially trial-eligible patients. Results: Overall, 271 patients were included and 73.8% died during the study period. Median OS was poorer than in the pivotal trials, regardless of medication and indication: 10.8 months (95% confidence interval [CI] 8.6-15.1) and 20.9 months (95% CI 14.9-29.0) for abiraterone, and 12.6 months (95% CI 10.5-18.2) and 16.0 months (95% CI 9.8—not reached) for enzalutamide, post and pre chemotherapy, respectively. Only 46% of patients were potentially “trial eligible” and in this subgroup OS improved. Factors influencing survival included baseline performance status, and baseline prostate-specific antigen, alkaline phosphatase, and albumin levels. Conclusions: Poorer prognostic features of non-trial eligible patients impact real-world outcomes of cancer medicines. Electronic record linkage of routinely collected healthcare data offers an opportunity to report outcomes on cancer medicines at scale and describe population demographics. The availability of such observational data to supplement clinical trial results enables patients and clinicians to make more informed treatment decisions, and policymakers to contextualise trial findings

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

The British sense of reserve has much to commend it, but itwould be difficult to codify in a constitution

The separation of powers is a fundamental feature of many written constitutions, but few of them incorporate the supportive principle of institutional self-restraint. In this post, Dr Aileen Kavanagh discusses how the British sense of reserve might inform such a principle and considers the implications of including this value in a proposed UK written constitution. While reserve might be a desirable quality, however, she concludes that codifying it would be problematic

El papel de los jueces en el marco de una carta de derechos: Una teoría de la contención judicial = The Role of Courts under a Bill of Rights: A Theory of Judicial Restraint

Resumen: Este trabajo tiene un doble objetivo. La primera parte ofrece una visión de conjunto del sistema de derechos configurado en el Reino Unido mediante la Human Rights Act de 1998, donde se trata de mostrar que, a pesar de haber sido descrito como un ejemplo destacado de la revisión judicial “débil” de constitucionalidad, el sistema británico muestra en realidad muchos rasgos de sutil fortaleza. En la segunda parte se toma como referencia la jurisprudencia de los tribunales británicos en el marco de dicha ley, con objeto de articular una teoría de la contención judicial. La conclusión es que, a la hora de determinar la fuerza o debilidad del poder judicial en un determinado sistema de revisión constitucional, necesitamos ir más allá de los mecanismos formales contenidos en los textos para analizar las doctrinas y los recursos que usan efectivamente los jueces cuando revisan la compatibilidad de la legislación con los derechos.Palabras clave: Revisión judicial en materia de derechos humanos, revisión judicial “débil”, supremacía judicial, contención judicialAbstract: The aim of this paper is twofold. First, it provides an overview of the system of the rights-based under the UK Human Rights Act 1998, trying to show that although it is often described as a leading exemplar of ‘weak-form’ constitutional review, in reality, the UK system displays many signs of subtle strength. Second, it adopts the decision making of the English courts under this bill of human rights to elaborate a theory of judicial restraint. The upshot is that when assessing any system of constitutional review in order to determine the strength or weakness of judicial power, we need to look beyond the formal textual mechanisms to explore the doctrines and devices judges use when reviewing legislation for compliance with rights.Keywords: Rights-based judicial review, weak-form judicial review, judicial supremacy, judicial restrain