Patient and clinician perspectives on clinical trials in transplant failure: a qualitative interview study

BACKGROUND: Transplant failure is associated with increased morbidity, mortality and poor quality of life. There is limited evidence to inform treatment decision-making when and after kidney transplants fail: randomised controlled trials are needed. We investigated the feasibility and acceptability of clinical trials into the management of kidney transplant failure, and explored research facilitators and barriers. METHODS: We undertook in-depth interviews with adults (aged ≥ 18 years) who had failing kidney transplants or had experienced kidney transplant failure, their relatives/friends, and healthcare professionals (HCPs). Participants were recruited from three UK NHS hospitals. Iterative purposive sampling of patient participants was undertaken, aiming for diversity with respect to personal characteristics, the type of transplant received (living/deceased-donor), whether the transplant was failing or had failed, and current kidney disease treatment. Purposive sampling of HCPs ensured diversity in sex, age, ethnicity, and role. Family and friends were recruited via posters and snowball sampling. Interviews investigated perspectives on clinical trials at the time of transplant failure. Sample size was determined by reaching theoretical saturation. We undertook inductive analysis according to constructivist grounded theory. RESULTS: Forty-one participants (17 HCPs/15 patients/9 relatives or friends) were interviewed. We identified the following categories: Facilitators to clinical trials: analytical thinking i.Recognition of the lack of evidence-individual and community equipoiseii.Motivation to advance stratified and personalised medicine Challenges to clinical trials: cognitive biases and heuristics iii.Status quo bias-preference for existing treatment regimensiv.Loss and risk aversion-fear of harm from researchv.Experiential learning and the availability heuristic-decisions based on recent or memorable cases These 5 categories were considered within the core category of 'Personal reasoning and clinical gatekeeping'. There was strong support for immunosuppression reduction trials, with stratification of people according to clinical and immunological subtypes. HCPs and patients supported trials after transplant failure but were reticent to engage in trials as a transplant was failing. CONCLUSIONS: Acknowledged individual and community equipoise appear to support trial delivery and recruitment. Umbrella trials may be needed to evaluate therapies in multiple patient subgroups.