Martin Howell

Important Outcomes for Kidney Transplant Recipients: A Nominal Group and Qualitative Study

BACKGROUND Immunosuppression is associated with a number of adverse outcomes, but typically it is the physician, not the patient, who decides on the drug regimen. The perspective of the patient in clinical decision making is increasingly recognized in other settings, but the perspectives of kidney transplant recipients are largely unknown. The aim of this study was to elicit patient perspectives and priorities for outcomes after transplant and the reasons underpinning these priorities. METHODS Outcome identification and ranking were undertaken using a focus/nominal group technique. Adult kidney transplant recipients, purposively sampled from 3 transplant centers, participated in 1 of 8 nominal groups. Each group (6-10 participants) listed and ranked outcomes relevant to immunosuppressant medications. RESULTS 57 participants identified 47 outcomes relevant to immunosuppression after transplant surgery. Transplant survival consistently was ranked more highly than any other outcome, followed by damage to other organs, survival, and cancer. Only 12% of participants ranked their own survival as more important than transplant survival. In contrast, the relative importance of side effects differed among participants. Themes underpinning priorities were concern for fatal and serious events; relevance to life circumstance; acceptance, trivialization, and tolerance; and future outlook. Participants described a willingness to tolerate side effects, dependent on personal relevance and ability to manage the side effect. CONCLUSIONS Transplant survival appears to be more important than life itself to kidney transplant recipients, suggesting that they may be willing to tolerate a higher level of immunosuppression than is assumed by clinicians and researchers.

Consumer involvement in topic and outcome selection in the development of clinical practice guidelines.

Background  Consumer involvement in guideline development is advocated, but minimal participation, such as a nominated consumer representative on a guideline working group, can inhibit their decision‐making power and contribution. Little is known about how to involve consumers more effectively in guideline development.

Assessment of kidney function in type 2 diabetes

Date written: April 2009

Time on dialysis and cancer risk after kidney transplantation.

Background Increasing time on dialysis is an established risk factor for certain cancer types for patients on dialysis, but the relationship between the time on dialysis and cancer risk after transplantation is unclear. We aimed to determine if the length of time on maintenance dialysis before the first kidney transplantation was associated with the risk of site-specific and overall incident cancers after transplantation. Methods Using the Australia and New Zealand Dialysis and Transplant Registry, we assessed the association between both all cancers (except for nonmelanocytic skin cancers) and site-specific cancer incidence and the duration on dialysis before the first transplantation using adjusted Cox proportional hazards and competing risk models. Results Over a median follow-up of 4.4 years (interquartile range, 1.7–7.7 years), the total cumulative incidence of all cancers after the first kidney transplantation was 15.0 per 1000 patient-years. There was a linear relationship between the duration of dialysis and the risk of cancer after transplantation (Ptrend=0.02). The excess risks for lung and urinary tract cancers were highest among recipients who had been on dialysis for the longest duration before transplantation (adjusted hazard ratio [95% confidence interval], 3.32 [1.00–11.4]; P=0.05 and 2.57 [1.33–4.95]; P=0.005, respectively). Conclusion Increasing time on dialysis is a significant risk factor for common solid organ cancers, such as lung cancer, and urinary tract cancers in kidney transplant recipients, irrespective of age. Strategies to improve cancer surveillance among recipients who had been on dialysis for a longer time may be warranted.

Donor renal function

Date written: August 2009

Eliciting patient preferences, priorities and trade-offs for outcomes following kidney transplantation: a pilot best–worst scaling survey

Objectives Eliciting preferences and trade-offs that patients may make to achieve important outcomes, can assist in developing patient-centred research and care. The pilot study aimed to test the feasibility of a case 2 best–worst scaling survey (BWS) to elicit recipient with kidney transplantation preferences after transplantation. Design Preferences for graft survival and dying, cancer, cardiovascular disease, diabetes, infection and side effects (gastrointestinal, weight-gain and appearance) were assessed in recipients with transplantation using a BWS (20 scenarios of nine outcomes). Participants chose ‘best’ and ‘worst’ outcomes. Responses were analysed using a multinomial logit model. Selected participants were interviewed. Outcomes Attribute coefficients and survey completion error rates. Results 81 recipients with transplantation were approached, and 39 (48%), mean age 50.5 years, completed the BWS. 4 (10%) surveys were invalid with major errors and of 35 remaining, 7 of 1400 (0.5%) choices were missing. –23 (59%) took >20 min to complete the survey. 1 was unable to finish, and 1 did not understand the survey. 2 (5%) found it very hard and 14 (35%) moderately hard. Most attribute coefficients were significant (p<0.05) and showed face validity. Graft survival was most important with normalised coefficients from 1 (95% CI 0.89 to 1.11) to 0.06 (95% CI −0.03 to 0.16) for 30 and 1 year duration, respectively. Attribute level coefficients decreased with increasing risk of adverse outcomes. Error rates of 20% and 2% were estimated for dominant attributes ‘100% risk of dying’ and ‘30 years graft survival’, respectively. 7 participants were interviewed regarding counterintuitive selection of ‘100% risk of dying’ as a ‘best’ outcome. Misunderstanding, not linking dying to graft survival and aversion to dialysis were reasons given. Conclusions Recipients with transplant recipients successfully completed a complex case 2 BWS with attribute coefficients having face validity with respect to duration of graft survival and risk of adverse outcomes. Areas for refinement to reduce complexity in design have been identified.

The Consistency and Reporting of Quality-of-Life Outcomes in Trials of Immunosuppressive Agents in Kidney Transplantation: A Systematic Review and Meta-analysis

BACKGROUND Shared decision making regarding immunosuppression in kidney transplantation requires an understanding of effects on quality of life (QoL). Our aim was to review the frequency and reliability of QoL measures reported in randomized controlled trials of maintenance immunosuppression following kidney transplantation. STUDY DESIGN Systematic literature review. SETTING & POPULATION Kidney transplant recipients enrolled in randomized trials of maintenance immunosuppression. SELECTION CRITERIA FOR STUDIES Systematic search of the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases to January 2014 identifying maintenance immunosuppression trials. An EQUATOR Network-endorsed checklist was used to assess QoL reporting and effect sizes estimated. INTERVENTION Maintenance immunosuppression (comparative studies, dose adjustment, and agent withdrawal). OUTCOMES Any quantitative patient-reported measure of physical, emotional, or social well-being. RESULTS Of 2,272 reports, 41 (2%; involving 4,549 participants from 23 trials) included QoL outcomes using 22 instruments (8 generic, 2 disease specific, and 12 symptom specific). Reporting was incomplete for the majority with 1 (4%) addressing all 11 items of the checklist, 4 (17%) addressing clinical significance, and 15 (65%) reporting outcomes selectively. Almost all (n = 96 [95%]) effect size estimates for 101 QoL outcomes (18 trials; 3,919 participants) favored the interventions, with 37 (37%) statistically significant. In comparison, 30 (73%) clinical outcomes favored the intervention and 13 (31%) were significant. LIMITATIONS QoL outcomes are commonly secondary outcomes and may not be indexed or found using text word searches. Effect sizes were estimated from different QoL measures, populations, and interventions. The small number of trials limits the ability to identify statistically significant associations between effect size and study-/patient-related factors. CONCLUSIONS QoL is infrequently reported in immunosuppression trials in kidney transplantation, appears subject to major biases, and thus may be unreliable for decision making.

Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

Background Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. Methods This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. Conclusions Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes.

Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops

Background Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. Methods We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. Results Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders—inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. Conclusions Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.

Healthcare and Research Priorities of Adolescents and Young Adults with Systemic Lupus Erythematosus: A Mixed-methods Study

Objective. Managing juvenile-onset systemic lupus erythematosus (SLE) is particularly challenging. The disease may be severe, adolescent patients have complex medical and psychosocial needs, and patients must navigate the transition to adult services. To inform patient-centered care, we aimed to identify the healthcare and research priorities of young patients with SLE and describe the reasons underpinning their priorities. Methods. Face-to-face, semistructured interviews and focus groups were conducted with patients with SLE, aged from 14 to 26 years, from 5 centers in Australia. For each of the 5 allocation exercises, participants allocated 10 votes to (1) research topics; research questions on (2) medical management, (3) prevention and diagnosis, (4) lifestyle and psychosocial; and (5) healthcare specialties, and discussed the reasons for their choices. Descriptive statistics were calculated for votes and qualitative data were analyzed thematically. Results. The 26 participants prioritized research that alleviated the psychological burden of SLE. They allocated their votes toward medical and mental health specialties in the management of SLE, while fewer votes were given to physiotherapy/occupational therapy and dietetics. The following 7 themes underpinned the participants’ priorities: improving service shortfalls, strengthening well-being, ensuring cost efficiency, minimizing family/community burden, severity of comorbidity or complications, reducing lifestyle disruption, and fulfilling future goals. Conclusion. Young patients with SLE value comprehensive care with greater coordination among specialties. They prioritized research focused on alleviating poor psychological outcomes. The healthcare and research agenda for patients with SLE should include everyone involved, to ensure that the agenda aligns with patient priorities, needs, and values.