ABSTRACT
Background: Trials involving adults who lack capacity to consent encounter a range of ethical and methodological challenges, resulting in these populations frequently being excluded from research. Excluding participants who lack capacity leads to unrepresentative trial populations which risks producing biased estimates of treatment effects, as well as denying these groups an equitable opportunity to participate in and benefit from research and limiting the ability to provide them with evidence-based care. The importance of improving the design and conduct of clinical trials to ensure the inclusion of under-served groups has received attention right across the global research community. However, currently, there is little evidence regarding the nature and extent of the challenges to including adults with impaired capacity in trials, nor strategies to improve the design and conduct of such trials. This qualitative study explored researchers' and healthcare professionals' experiences of the barriers and facilitators to conducting trials involving adults lacking capacity to consent. Method(s): Semi-structured interviews were conducted remotely with 26 researchers and healthcare professionals with experience in a range of roles, trial populations, and settings across the United Kingdom. This included trials in emergency conditions such as cardiac arrest, surgical, and trauma-related trials, as well as people with dementia and those living in care homes. Participants included trial managers, chief investigators, and research nurses. Interviews were audiorecorded and transcribed verbatim. Data were analyzed using thematic analysis. Result(s): A number of inter-related barriers and facilitators were identified and mapped against key trial processes including when making trial design decisions, navigating ethical approval, assessing capacity, identifying and involving alternative decision-makers, and when revisiting consent. Three themes were identified: (1) the perceived and actual complexity of trials involving adults lacking capacity, (2) importance of having access to appropriate support and resources, and (3) need for building greater knowledge and expertise to support future trials. Conducting trials involving adults who lack capacity was facilitated by having prior experience with these populations, effective communication between research teams, contributions from public involvement, and the availability of additional data to inform the trial. Barriers included the complexity of the legal frameworks and ethical approval processes, the role of gatekeepers, a lack of access to expertise and training, and the resource-intensive nature of these trials. Participants also identified a range of context-specific recruitment issues and highlighted the importance of ''designing in'' flexibility and use of adaptive strategies which were especially important for trials during the COVID-19 pandemic. Participants identified the need for further training and support. A number of recommendations are made for research funders and those designing and conducting trials, as well as at a policy and research governance level. Conclusion(s): Researchers encountered a number of barriers, including both generic and context or population-specific challenges, which may be reinforced by wider factors such as resource limitations and knowledge deficits. Greater access to expertise and training, and the development of supportive interventions and tailored guidance, is urgently needed in order to build research capacity in this area and facilitate the successful delivery of trials involving this under-served population.
ABSTRACT
Background: Clinical trials involving patients who are unable to provide consent rely on proxies to make a decision on the patient's behalf. The proxy's decision should be based on the patient's wishes and preferences. However, patients rarely discuss their preferences about research, and proxies find it challenging to determine what their wishes would be. While improving consent in trials has been the focus of much research in recent decades, the more conceptually complex area of proxy consent has remained largely unexplored. A global increase in conditions such as dementia has led to an urgent need for trials involving populations who require proxy consent, and the necessity to conduct trials with large numbers of critically ill patients during the COVID-19 pandemic has made this need even more pressing. However, interventions to improve and support proxy decision-making for research are hampered by a lack of understanding about what constitutes decision quality in this context. This presentation reports a concept synthesis that was conducted to develop the first conceptualization of what constitutes ''good'' proxy consent decisions. A concept synthesis enables a greater understanding of a concept through identifying the existing theoretical strands that define that concept, with the conceptual knots then re-tied to form a stronger, more coherent ''tapestry of theory.'' Methods: Literature was identified through conducting iterative searches of databases including MEDLINE and CINAHL. Literature which captured domains of both proxy decision-making (the process) and decision quality (the decision itself) were reviewed. Concepts of interest were identified and assessed according to established principle-based criteria used in concept syntheses. Data were then extracted and synthesized to generate a concept matrix. This was then used to create a concept map, with quality descriptors developed for each stage. Result(s): Elements of decision quality were identified across three stages of decision-making: (1) the preparation stage requires the proxy to have knowledge and understanding about the trial and any associated risks and benefits, as well as about their role, and involves values clarification and preference elicitation;(2) the decision-making stage includes both deliberation and determination processes, with the proxy seeking to make a decision about participation that is congruent with the patient's values;and (3) the outcome of the decision-either the proxy agreeing or declining participation-is in accordance with the patient's preferences as determined by the proxy. These stages of proxy decision-making may be influenced by affective factors experienced by the proxy such as decisional uncertainty, decisional conflict, satisfaction, and regret. Quality descriptors have been developed that map against the three stages of decision-making, such that a ''good'' proxy consent decision can be said to occur where the proxy is adequately prepared, supported, and satisfied, and when a preference-linked outcome is achieved. Conclusion(s): Proxy decisions about trial participation are ethically complex, and interventions are needed to address the challenges of providing proxy consent. This conceptualization provides an essential first step toward the future development of interventions to enhance the quality of proxy decision-making and ensuring that proxy consent represents patients' values and preferences.