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
We examined PrEP use, condomless anal sex (CAS), and PrEP adherence among men who have sex with men (MSM) attending sexual health clinics in Wales, UK. In addition, we explored the association between the introduction of measures to control transmission of SARS-CoV-2 on these outcomes. We conducted an ecological momentary assessment study of individuals in receipt of PrEP in Wales. Participants used an electronic medication cap to record PrEP use and completed weekly sexual behaviour surveys. We defined adherence to daily PrEP as the percentage of CAS episodes covered by daily PrEP (preceded by ≥ 3 days of PrEP and followed by ≥ 2 days). Sixty participants were recruited between September 2019 and January 2020. PrEP use data prior to the introduction of control measures were available over 5785 person-days (88%) and following their introduction 7537 person-days (80%). Data on CAS episodes were available for 5559 (85%) and 7354 (78%) person-days prior to and following control measures respectively. Prior to the introduction of control measures, PrEP was taken on 3791/5785 (66%) days, there were CAS episodes on 506/5559 (9%) days, and 207/406 (51%) of CAS episodes were covered by an adequate amount of daily PrEP. The introduction of pandemic-related control measures was associated with a reduction in PrEP use (OR 0.44, 95%CI 0.20-0.95), CAS (OR 0.35, 95%CI 0.17-0.69), and PrEP adherence (RR = 0.55, 95%CI 0.34-0.89) and this may have implications for the health and wellbeing of PrEP users and, in addition to disruption across sexual health services, may contribute to wider threats across the HIV prevention cascade.