James Neuberger

Across European legal systems, there is a consensus on the importance of consent in medical ethics as recently emphasised by the European Court of Human Rights in Pindo Mulla v Spain. Yet, consent in medical law poses several challenges in practice which includes the need to reduce mistakes in the consent process. We argue that consent is scalar and includes ‘strong’ consent (where a patient has maximum capacity to express a fully informed, voluntary decision) to weak consent (where a patient has said ‘yes’ but with limited understanding or liberty. We propose a ‘model of disaggregating consent’ which highlights the range of values that consent protects albeit to varying degrees in different cases. We apply our model to the example of organ donation and organ transplantation to illuminate how our model paves the way for improving decision-making in the consent process by factoring in the pluralistic values at play.

Increasing the availability of suitable organs is essential for life-saving transplant surgery. We highlight the importance of consent to deceased organ donation and discuss whether a ‘blanket ban’ on attaching conditions to a donation is appropriate by analysing relevant legal, ethical, and clinical considerations. The introduction highlights key issues in this area and defines the different kinds of conditional donations. We focus on conditions that seek to limit ‘who’ might receive an organ. The article outlines the current approach to conditions attached to the donation of organs. We identify key models of conditional organ donation: (a) no conditions allowed; (b) permit all conditions; and (c) permit some conditions. The third model of permitting some conditions includes permitting conditions except those contrary to equality and non-discrimination law, or permitting conditions as exceptions, or permitting conditions, but only as advisory. We demonstrate that there is room for disagreement about the permissibility of each model and argue that there is potential for reforming the law in this area to achieve the appropriate balance between protecting the personal autonomy of donors with the wider interests of protecting the organ allocation system.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator–activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.

The first successful human liver transplant (LT) was done over 60 years ago; since the early pioneering days, this procedure has become a routine treatment with excellent outcomes for the great majority of recipients. Over the last six decades, indications have evolved. Use of LT for hepatic malignancy is becoming less common as factors that define a successful outcome are being increasingly defined, and alternative therapeutic options become available. Both Hepatitis B and C virus associated liver disease are becoming less common indications as medical treatments become more effective in preventing end-stage disease. Currently, the most common indications are alcohol-related liver disease and metabolic associated liver disease. The developing (and controversial) indications include acute on chronic liver failure, alcoholic hepatitis and some rarer malignancies such as non-resectable colorectal cancer liver metastases, neuroendocrine tumours and cholangiocarcinoma. Candidates are becoming older and with greater comorbidities, A relative shortage of donor organs remains the greatest cause for reducing access to LT; therefore, various countries have developed transparent approaches to allocation of this life saving and life enhancing resource. Reliance on prognostic models has gone some way to improve transparency and increase equity of access but these approaches have their limitations.

The supply of blood, blood products and components in the UK, as elsewhere, is safe, although there is no cause for complacency. Use of blood, blood products and components is not without risk of morbidity and mortality. Transfusion-transmitted infections (TTIs) continue to occur and may severely affect the health and welfare of recipients. As indicated by recent and current inquiries, public interest in these TTIs is huge. The risk of TTI can be mitigated but not abolished. Measures to reduce risk include screening of donors, testing of donations and, where appropriate, treatment of donations. The introduction of newer screening tests might identify some infectious donations but come at a cost, which could exceed a justifiable limit. Thus, the recognition, detection, reporting and investigation of cases of possible TTIs need to be improved. Recipients of blood should understand that, although transfusion in the UK is safe, it is not free of risk and so should be provided with full information so that properly informed consent can be given.