Ethical and legal issues in mitochondrial transfer

The US National Academies of Science, Engineering and Medicine recently provided conditional endorsement for mitochondrial transfer. While its approach is more conservative in some respects than that of the United Kingdom (which passed its own regulations in 2015 ), it marks a significant policy development for a potentially large implementer of this emerging intervention. In this perspective, we consider some of the ethical and legal aspects of these policy responses

Understanding the care.data conundrum: new information flows for economic growth

The analysis of data from electronic health records aspires to facilitate healthcare efficiencies and biomedical innovation. There are also ethical, legal and social implications from the handling of sensitive patient information. The paper explores the concerns, expectations and implications of the National Health Service (NHS) England care.data programme: a national data sharing initiative of linked electronic health records for healthcare and other research purposes. Using Nissenbaum’s contextual integrity of privacy framework through a critical science and technology studies (STS) lens, it examines the way technologies and policies are developed to promote sustainability, governance and economic growth as the de facto social values, while reducing privacy to an individualistic preference. The state, acting as a new, central data broker reappropriates public ownership rights and establishes those information flows and transmission principles that facilitate the assetisation of NHS datasets for the knowledge economy. Various actors and processes from other contexts attempt to erode the public healthcare sector and privilege new information recipients. However, such data sharing initiatives in healthcare will be resisted if we continue to focus only on the monetary and scientific values of these datasets and keep ignoring their equally important social and ethical values

Research utilisation and knowledge mobilisation in the commissioning and joint planning of public health interventions to reduce alcohol-related harms: a qualitative case design using a cocreation approach

Background: Considerable resources are spent on research to establish what works to improve the nation’s health. If the findings from this research are used, better health outcomes can follow, but we know that these findings are not always used. In public health, evidence of what works may not ‘fit’ everywhere, making it difficult to know what to do locally. Research suggests that evidence use is a social and dynamic process, not a simple application of research findings. It is unclear whether it is easier to get evidence used via a legal contracting process or within unified organisational arrangements with shared responsibilities. Objective: To work in cocreation with research participants to investigate how research is utilised and knowledge mobilised in the commissioning and planning of public health services to reduce alcohol-related harms. Design, setting and participants: Two in-depth, largely qualitative, cross-comparison case studies were undertaken to compare real-time research utilisation in commissioning across a purchaser–provider split (England) and in joint planning under unified organisational arrangements (Scotland) to reduce alcohol-related harms. Using an overarching realist approach and working in cocreation, case study partners (stakeholders in the process) picked the topic and helped to interpret the findings. In Scotland, the topic picked was licensing; in England, it was reducing maternal alcohol consumption. Methods: Sixty-nine interviews, two focus groups, 14 observations of decision-making meetings, two local feedback workshops (n = 23 and n = 15) and one national workshop (n = 10) were undertaken. A questionnaire (n = 73) using a Behaviourally Anchored Rating Scale was issued to test the transferability of the 10 main findings. Given the small numbers, care must be taken in interpreting the findings. Findings: Not all practitioners have the time, skills or interest to work in cocreation, but when there was collaboration, much was learned. Evidence included professional and tacit knowledge, and anecdotes, as well as findings from rigorous research designs. It was difficult to identify evidence in use and decisions were sometimes progressed in informal ways and in places we did not get to see. There are few formal evidence entry points. Evidence (prevalence and trends in public health issues) enters the process and is embedded in strategic documents to set priorities, but local data were collected in both sites to provide actionable messages (sometimes replicating the evidence base). Conclusions: Two mid-range theories explain the findings. If evidence has saliency (relates to ‘here and now’ as opposed to ‘there and then’) and immediacy (short, presented verbally or visually and with emotional appeal) it is more likely to be used in both settings. A second mid-range theory explains how differing tensions pull and compete as feasible and acceptable local solutions are pursued across stakeholders. Answering what works depends on answering for whom and where simultaneously to find workable (if temporary) ‘blends’. Gaining this agreement across stakeholders appeared more difficult across the purchaser–provider split, because opportunities to interact were curtailed; however, more research is needed. Funding: This study was funded by the Health Services and Delivery Research programme of the National Institute for Health Research

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away from a GE evaluation process that currently focuses only on risk assessment and identifying ever diminishing marginal hazards, to a regulatory approach that more objectively evaluates and communicates the likely impact of approving a new GE plant or animal on agricultural production systems