Constructing authentic decisions: proxy decision making for research involving adults who lack capacity to consent

Research involving adults who lack capacity to consent relies on proxy (or surrogate) decision making. Proxy decisions about participation are ethically complex, with a disparity between normative accounts and empirical evidence. Concerns about the accuracy of proxies’ decisions arise, in part, from the lack of an ethical framework which takes account of the complex and morally pluralistic world in which proxy decisions are situated. This qualitative study explored the experiences of family members who have acted as a research proxy in order to develop an understanding of the ethical concepts involved, and the interactions between those concepts. Proxies described a complex process of respecting the wishes and preferences of the person they represented, whist integrating preferences with what they viewed as being in the interests of the person. They aimed to make a decision that was ‘best’ for the person and protected them from harm; they also aimed to make the ‘right’ decision, viewed as being authentic to the person’s values and life. Decisions were underpinned by the relationship between the person and their proxy, in which both trust and trustworthiness were key. Proxies’ decisions, based both on respect for the person and the need to protect their interests, arose out of their dual role as both proxy and carer. The findings raise questions about accounts which rely on existing normative assumptions with a focus on accuracy and discrepancy, and which fail to take account of the requirement for proxies to make authentic decisions that arise out of their caring obligations

Partial anomalous pulmonary venous return mimics arterial positioning after central line placement for plasmapheresis

Case: A 61-year-old male who was status post right single lung transplant complicated by grade three primary graft dysfunction was admitted and mechanically ventilated for hypoxic respiratory failure. Donor specific antibody testing to human leukocyte antigens was positive. The protocol for antibody-mediated transplant rejection was initiated. One aspect of the protocol was a series of plasmapheresis procedures. In advance of the first plasmapheresis, central line placement was attempted via the left internal jugular vein. A chest x-ray showed a line that terminated to the left of the midline and raised concern for arterial placement (Figure 1). Blood gases from the line were: pH 7.72, pCO2 21 mmHg, pO2 369 mmHg, bicarbonate 28.4 mmol/L.Alex J. Griffith (Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital), Victoria Ray (MD, Department of Anesthesiology, University of Wisconsin Hospital), William N. Rose (MD, Department of Emergency Medicine, University of Wisconsin Hospital)Includes bibliographical reference

The positive impact of legal advice and services on the mental wellbeing of UK veterans

Law has been recognised as a significant social determinant of health, however, micro-level legal advice interventions are underexplored. The dearth of research concerning the experience of British veterans highlights the need for uniquely tailored support services. This need is emphasised by the pervasiveness of mental health issues amongst this population. We investigate the feasibility of remotely delivered legal advice as a social intervention for supporting the mental wellbeing of UK veterans. This is based on the Warwick-Edinburgh Mental Wellbeing Scale results from 67 participants, who completed a pre and post legal intervention survey. Average WEMWBS results were higher post-intervention, particularly in participants with pre-identified mental health issues. The difference in overall scores pre and post intervention is statistically significant (p = 0.034). A correlation matrix identifies two variables, with one contributing to 59% variance (LV2). These are identified as “Affective” (LV2), and “Cognitive” (LV1). The difference between LV2 results pre and post intervention was significant (p = 0.016). Findings highlight the importance of individualised interventions for veterans. Free, remotely delivered, tailored legal advice and support shows feasibility as a social intervention due to its ability to encourage emotional disclosure, something which the veteran population can struggle with

Yeast mitochondrial HMG proteins: DNA-binding properties of the most evolutionarily divergent component of mitochondrial nucleoids

Comparative biochemical analysis of mtHMG proteins from distantly related yeast species revealed that they exhibit a preference for recombination/replication intermediates. We discuss how these biochemical characteristics relate to the role of mtHMG proteins in mtDNA compaction and evolution.Yeast mtDNA is compacted into nucleoprotein structures called mitochondrial nucleoids (mt-nucleoids). The principal mediators of nucleoid formation are mitochondrial high-mobility group (HMG)-box containing (mtHMG) proteins. Although these proteins are some of the fastest evolving components of mt-nucleoids, it is not known whether the divergence of mtHMG proteins on the level of their amino acid sequences is accompanied by diversification of their biochemical properties. In the present study we performed a comparative biochemical analysis of yeast mtHMG proteins from Saccharomyces cerevisiae (ScAbf2p), Yarrowia lipolytica (YlMhb1p) and Candida parapsilosis (CpGcf1p). We found that all three proteins exhibit relatively weak binding to intact dsDNA. In fact, ScAbf2p and YlMhb1p bind quantitatively to this substrate only at very high protein to DNA ratios and CpGcf1p shows only negligible binding to dsDNA. In contrast, the proteins exhibit much higher preference for recombination intermediates such as Holliday junctions (HJ) and replication forks (RF). Therefore, we hypothesize that the roles of the yeast mtHMG proteins in maintenance and compaction of mtDNA invivo are in large part mediated by their binding to recombination/replication intermediates. We also speculate that the distinct biochemical properties of CpGcf1p may represent one of the prerequisites for frequent evolutionary tinkering with the form of the mitochondrial genome in the CTG-clade of hemiascomycetous yeast species

'There's more to life than money and health': family caregivers' views on the role of Power of Attorney in proxy decisions about research participation for people living with dementia

People living with dementia may experience difficulties when making decisions for themselves in the later stages of the condition. While there are mechanisms in England and Wales for appointing an attorney to make decisions about welfare and finances on their behalf, there are no provisions for appointing an attorney to make future decisions about research participation. This is despite a growing focus on Advanced Care Planning and other processes that provide opportunities to discuss future preferences and ensure that decisions are made in line with those preferences. This qualitative study with 15 family caregivers who had acted as research proxies explored the role of Power of Attorney in their decisions about research, and their views about extending current legal arrangements to include research. Five themes were identified: the holistic nature of decision-making; the ‘power’ of attorney; making decisions by putting yourself in their shoes; support for bringing research under the umbrella of attorney arrangements and a unifying theme of trusting relationships. Legal provisions for prospectively appointing a research proxy may encourage discussion about future wishes and so enable decisions about research to be made that are in accordance with the person’s preferences and wishes. However, further consultation with the public including people living with dementia and their families, and a range of stakeholders is needed. Providing guidance to families, people living with dementia and the wider research community may provide greater clarity and improve decision-making in the meantime

Research involving adults lacking capacity to consent: a content analysis of participant information sheets for consultees and legal representatives in England and Wales

Background: Research involving adults who lack the capacity to provide informed consent can be challenging. In England and Wales there are legal provisions for consulting with others who know the person with impaired capacity. The role of the ‘proxy’ (or ‘surrogate’) is to advise researchers about the person’s wishes and feelings or to provide consent on the person’s behalf for a clinical trial of a medicine. Information about the study is usually provided to the proxy; however, little information is available to proxies about their role, or the appropriate legal and ethical basis for their decision, to help inform their decision-making. The aim of this study was to analyse the written information that is provided to consultees and legal representatives. Methods: Studies including adults lacking capacity to consent which utilised consultees or legal representatives were identified using the UK Clinical Trials Gateway database. A representative sample (n = 30) were randomly selected. Information sheets and other study documents provided to proxies were obtained, and relevant content was extracted. Content analysis was conducted through four stages: decontextualisation of the unit of analysis, recontextualisation, categorisation, and compilation. The data were summarised narratively according to each theme and category. Results Considerable variation was found in the written information sheets provided to proxies. Most directed proxies to consider the wishes and feelings of the person who lacked capacity and to consult with others during the decision-making process. However, a small number of studies extended the scope of the proxy’s role to consider the person’s suitability or eligibility for the study. Particular discrepancies were found in information provided to those acting as consultees or legal representatives in a professional, as opposed to a personal, capacity. Incorrect uses of terminology were frequently found, and a small number of studies inaccurately interpreted the law. Conclusions: Despite undergoing ethical review, study documents lacked essential information, incorrectly used terminology, and conflated professionals’ clinical and representation roles. Future recommendations include ensuring proxies are provided with adequate and accurate information which complies with the legal frameworks. Further research is needed to explore the information and decision-making needs of those acting as consultees and legal representatives

Healthcare professionals’ understanding of the legislation governing research involving adults lacking mental capacity in England and Wales: a national survey

Objective To examine health and social care professionals’ understanding of the legislation governing research involving adults lacking mental capacity in England and Wales. Methods A cross-sectional online survey was conducted using a series of vignettes. Participants were asked to select the legally authorised decision-maker in each scenario and provide supporting reasons. Responses were compared to existing legal frameworks and analysed according to their level of concordance. Results One hundred and twenty-seven professionals participated. Levels of discordance between responses and the legal frameworks was high across all five scenarios (76% – 82%). Nearly half of the participants (46%) provided responses that were discordant in all scenarios. Only 2 participants (2%) provided concordant responses across all five scenarios. Participants failed to recognise that the basis for enrolment was the person’s ‘presumed will’. ‘Best interests’ was overwhelmingly cited as the ethical basis for the decision. Discussion Participants demonstrated a lack of knowledge about the legal frameworks, the locus of authority, and the legal basis for decision–making. The findings raise concern about the accessibility of research for those who lack capacity, the ability to conduct research involving such groups, and the impact on the evidence-base for their care. Conclusion This is the first study to examine health and social care professionals’ knowledge and understanding of the dual legal frameworks in the UK. Health and social care professionals’ understanding and attitudes towards research involving adults with incapacity may warrant further in-depth exploration. The findings from this survey suggest that greater training and education is required

'It's a tough decision': A qualitative study of proxy decision-making for research involving adults who lack capacity to consent in England and Wales

Research into dementia and other conditions connected with cognitive impairments is essential but conducting research with populations who lack capacity to provide consent involves a number of ethical, legal and practical challenges. In England and Wales, family members can act as a consultee or legal representative on behalf of someone who lacks capacity. However, there is a paucity of research about how family members make decisions concerning research participation. OBJECTIVE: To explore family members' experiences of proxy decision-making for research. Understanding how proxy decisions are made could lead to interventions to support greater inclusion of individuals in research who have impaired decision-making capacity. METHODS: Semi-structured interviews were conducted with a purposive sample of 17 family members who had experience as a proxy for making decisions about participation in research, including those who had agreed to participation and those who declined. Thematic analysis was used to examine experiences and generate findings for research practice and to develop future supportive interventions. RESULTS: Proxy decision-making is highly contextualised. Proxies balance a number of factors when deciding about research participation, including the person's values and preferences, within the specific context of the study, and the practicalities of being involved. Proxies use these factors to construct a decision that is authentic to the person they care for. CONCLUSIONS: Proxy decision-making for research is a complex process with inter-woven layers of decision-making. Decisions can be problematic for some proxies who may benefit from decision support to make an informed decision about research participation on behalf of a family member

Development of a decision support intervention for family members of adults who lack capacity to consent to trials

Background Informed consent is required for participation in clinical trials, however trials involving adults who lack capacity to consent require different enrolment processes. A family member usually acts as a proxy to make a decision based on the patient’s ‘presumed will’, but these decisions can be challenging and families may experience an emotional and decisional burden. Decisions made on behalf of others are conceptually different from those made for ourselves. Innovations have been developed to improve informed consent processes for research, including a number of decision aids, however there are no interventions for proxies who are faced with more complex decisions. This article outlines the development of a novel decision aid to support families making decisions about research participation on behalf of an adult who lacks capacity to consent. Methods Decision support interventions should be developed using rigorous and evidence-based methods. This intervention was developed using MRC guidance for the development of complex interventions, and a conceptual framework for the development and evaluation of decision aids for people considering taking part in a clinical trial. The intervention was informed by a systematic review and analysis of existing information provision. Previous qualitative research with families who acted as proxies enabled the development of a theoretical framework to underpin the intervention. The intervention was iteratively developed with the involvement of lay advisors and relevant stakeholders. Results Previous research, theoretical frameworks, and decision aid development frameworks were used to identify and develop the intervention components. The decision aid includes information about the proxy’s role and utilises a values clarification exercise and decision support methods to enable a more informed and better-quality decision. Stakeholders, including those representing implementers and receivers of the intervention, contributed to the design and comprehensibility of the decision aid to ensure that it would be acceptable for use. Conclusions Frameworks for the development of decision aids for people considering participating in a clinical trial can be used to develop interventions for family members acting as proxy decision-makers. The decision support tool is acceptable to users. Feasibility testing and outcome measure development is required prior to any evaluation of its effectiveness

Protection by exclusion? The (lack of) inclusion of adults who lack capacity to consent to research in clinical trials in the UK

Background Around two million adults in the UK have significantly impaired decision-making capacity. However, there are concerns that this population is under-represented in research, due in part to the challenges around obtaining consent. Under-representation of populations denies those who would have wanted to participate the opportunity to make a contribution to society, but also fails to generate results that are applicable to them. Consequently, the evidence base for their care is poorer than for other populations. We recently published in this journal an analysis of Participant Information Sheets provided to consultees and legal representatives of adults who lack capacity and noted the small number of trials designed to include adults who lack capacity. In order to understand how many adults who lack capacity to consent are actually enrolled in clinical trials, we further explored how many of the participants lacked capacity, and who acted as a consultee or legal representative on their behalf. Main text The ISRCTN registry was searched for UK clinical trials in conditions commonly associated with cognitive impairment that were designed to include (or not exclude) adults who lack capacity to consent. Details about participants and capacity status were obtained from published data or directly from the trial teams. Of the 80 retrieved clinical trials that had completed in the previous 3 years, we identified 15 which included adults who lack capacity to consent. Data regarding participants’ capacity status were not available for five trials. Where capacity was reported, 5–100% participants lacked capacity to consent. Trials predominantly utilised personal consultees/legal representatives; however, 39% (634/1631) of participants required a professional to act as consultee/legal representative. Conclusions Only a small number of trials including adults who lacked capacity were identified. The majority of participants were represented by a personal consultee/legal representative; however, between 21 and 100% of participants across five trials required the involvement of a professional, suggesting it is not uncommon. Data relating to capacity status were rarely reported, potentially masking the under-representation of adults who lack capacity. The findings may help researchers and funders target resources towards studies involving under-represented populations to increase the much-needed evidence base for their care and treatment