Operationalizing Equity, Inclusion, and Access in Research Practice at a Large Academic Institution.

INTRODUCTION: Healthcare advances are hindered by underrepresentation in prospective research; sociodemographic, data, and measurement infidelity in retrospective research; and a paucity of guidelines surrounding equitable research practices. OBJECTIVE: The Joint Research Practices Working Group was created in 2021 to develop and disseminate guidelines for the conduct of inclusive and equitable research. METHODS: Volunteer faculty and staff from two research centers at the University of Pennsylvania initiated a multi-pronged approach to guideline development, including literature searches, center-level feedback, and mutual learning with local experts. RESULTS: We developed guidelines for (1) participant payment and incentives; (2) language interpretation and translation; (3) plain language in research communications; (4) readability of study materials; and (5) inclusive language for scientific communications. Key recommendations include (1) offer cash payments and multiple payment options to participants when required actions are completed; (2) identify top languages of your target population, map points of contact, and determine available interpretation and translation resources; (3) assess reading levels of materials and simplify language, targeting 6th- to 8th-grade reading levels; (4) improve readability through text formatting and style, symbols, and visuals; and (5) use specific, humanizing terms as adjectives rather than nouns. CONCLUSIONS: Diversity, inclusion, and access are critical values for research conduct that promotes justice and equity. These values can be operationalized through organizational commitment that combines bottom-up and top-down approaches and through partnerships across organizations that promote mutual learning and synergy. While our guidelines represent best practices at one time, we recognize that practices evolve and need to be evaluated continuously for accuracy and relevance. Our intention is to bring awareness to these critical topics and form a foundation for important conversations surrounding equitable and inclusive research practices.

Quantifying Risk Tolerance Among Potential Living Kidney Donors With the Donor-Specific Risk Questionnaire.

RATIONALE & OBJECTIVE: Enhanced informed consent tools improve patient engagement. A novel visual aid measured potential donors' risk tolerance to postdonation kidney failure and assessed if the closeness of the relationship to the intended recipient altered willingness to accept risk. STUDY DESIGN: Cross-sectional analysis of donor evaluations at the time of enrollment into a longitudinal mixed-methods study between November 2014 and February 2016. SETTING & PARTICIPANTS: Three US kidney transplant centers. English-speaking adults presenting for in-person living kidney donor evaluation. EXPOSURE: Closeness of the relationship between the potential living donor and intended recipient. OUTCOME: Willingness to accept postdonation kidney failure. ANALYTICAL APPROACH: The Donor-Specific Risk Questionnaire, a dot matrix visual diagram, was used to measure willingness to accept kidney failure risk. Multivariable logistic regression assessed associations between risk acceptance and data from social science instruments, which measured donors' perceived closeness with the recipient. Qualitative data were analyzed thematically per grounded theory. RESULTS: 307 participants (response rate: 86%) completed testing. 96% indicated a willingness to accept a risk of kidney failure of 0.9% or greater. Those who were older (OR, 0.98 [95% CI, 0.96-0.99]), women (OR, 0.54 [95% CI, 0.31-0.93]), and Black (OR, 0.25 [95% CI, 0.08-0.76]) were less likely to be in the medium versus low willingness to accept risk group. Closeness of the relationship to the recipient was independently associated with greater risk acceptance (for every 1-point greater closeness score, odds ratios for being in the medium and high willingness to accept risk groups were 1.21 [95% CI, 1.03-1.41] and 2.42 [95% CI, 1.53-3.82] compared with being in the low willingness to accept risk group). With the exception of parental relationships, biological linkages were not associated with accepting higher kidney failure risk. LIMITATIONS: First demonstration of visual aid that used one risk estimate of kidney failure provided to all participants. Risk estimates were not customized to different demographic groups. CONCLUSIONS: Relationship closeness was independently associated with a greater willingness to accept postdonation kidney failure. Visual aids can provide transplant teams with individualized donor perspectives on risk thresholds and can potentially facilitate greater patient-centered care for living donors.

Transplant candidates' perceptions of informed consent for accepting deceased donor organs subjected to intervention research and for participating in posttransplant research.

Deceased donor organ intervention research holds promise for increasing the quantity and quality of organs for transplantation by minimizing organ injury and optimizing function. Such research will not progress until ethical, regulatory, and legal issues are resolved regarding whether and how to obtain informed consent from transplant candidates offered intervention organs given time constraints intrinsic to distribution. This multi-center, mixed-methods study involved semi-structured interviews using open- and closed-ended questions to assess waitlisted candidates' preferences for informed consent processes if offered an organ after undergoing intervention. Data were analyzed thematically. Sixty-one candidates participated (47% participation rate). Most were male (57%), white (61%), with a mean age of 56 years. Most candidates (79%) desired being informed that the organ offered was an intervention organ before accepting it, and were likely to accept an intervention organ if organ quality was good (defined as donor age 30) (81%), but fewer candidates would accept an intervention organ if quality was moderate (ie, donor age 50) (26%). Most perceived informed consent important for decision-making, while others considered it unnecessary given medical necessity to accept an organ and trust in their physician. Our findings suggest that most candidates desire an informed consent process before accepting an intervention organ and posttransplant data collection.

Outcomes for individuals turned down for living kidney donation.

BACKGROUND: A better understanding of the consequences of being turned down for living kidney donation could help transplant professionals to counsel individuals considering donation. METHODS: In this exploratory study, we used survey instruments and qualitative interviews to characterize nonmedical outcomes among individuals turned down for living kidney donation between July 1, 2010 and December 31, 2013. We assembled a comparator group of kidney donors. RESULTS: Among 83 turned-down donors with contact information at a single center, 43 (52%) participated in the study (median age 53 years; 53% female; 19% black). Quality of life, depression, financial stress, and provider empathy scores were similar between individuals turned down for donation (n = 43) and donors (n = 128). Participants selected a discrete choice response to a statement about the overall quality of their lives; 32% of turned-down donors versus 7% of donors (P < 0.01) assessed that their lives were worse after the center's decision about whether they could donate a kidney. Among turned-down donors who reported that life had worsened, 77% had an intended recipient who was never transplanted, versus 36% among individuals who assessed life as the same or better (P = 0.02). In interviews, the majority of turned-down donors reported emotional impact, including empathy, stress, and other challenges, related to having someone in their lives with end-stage kidney disease. CONCLUSIONS: Generic instruments measuring quality of life, depression, financial stress, and provider empathy revealed no significant differences between kidney donors and turned-down donors. However, qualitative interviews revealed preliminary evidence that some turned-down donors experienced emotional consequences. These findings warrant confirmation in larger studies.

Automated Reminders and Physician Notification to Promote Immunosuppression Adherence Among Kidney Transplant Recipients: A Randomized Trial.

BACKGROUND: Immunosuppression nonadherence increases the risk for kidney transplant loss after transplantation. Wireless-enabled pill bottles have created the opportunity to monitor medication adherence in real time. Reminders may help patients with poor memory or organization. Provision of adherence data to providers may motivate patients to improve adherence and help providers identify adherence barriers. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Kidney transplant recipients (n=120) at a single center. INTERVENTION: Participants were provided wireless pill bottles to store tacrolimus and record bottle openings. Participants were randomly assigned 1:1:1 to adherence monitoring with customized reminders (including alarms, texts, telephone calls, and/or e-mails), monitoring with customized reminders plus provider notification (every 2 weeks, providers received notification if adherence decreased to <90% during that period), or wireless pill bottle use alone (control). OUTCOMES: The main outcome was bottle-measured tacrolimus adherence during the last 90 days of the 180-day trial. A secondary outcome was tacrolimus whole-blood concentrations at routine clinical visits. MEASUREMENTS: Adherence for the primary outcome was assessed via wireless pill bottle openings. RESULTS: Mean participant age was 50 years; 60% were men, and 40% were black. Mean adherence was 78%, 88%, and 55% in the reminders, reminders-plus-notification, and control arms (P<0.001 for comparison of each intervention to control). Mean tacrolimus levels were not significantly different between groups. LIMITATIONS: The study did not assess clinical end points. Participants and study coordinators were not blinded to intervention arm. CONCLUSIONS: Provider notification and customized reminders appear promising in helping patients achieve better medication adherence, but these strategies require evaluation in trials powered to detect differences in clinical outcomes.

Two Randomized Controlled Pilot Trials of Social Forces to Improve Statin Adherence among Patients with Diabetes.

BACKGROUND: Medication nonadherence is an important obstacle to cardiovascular disease management. OBJECTIVE: To improve adherence through real-time feedback based on theories of how social forces influence behavior. DESIGN: Two randomized controlled pilot trials called PROMOTE and SUPPORT. Participants stored statin medication in wireless-enabled pill bottles that transmitted adherence data to researchers. PARTICIPANTS: Adults with diabetes and a history of low statin adherence based on pharmacy refills (i.e., Medication Possession Ratio [MPR] <80% in the pre-randomization screening period). INTERVENTION: In PROMOTE, each participant was randomized to 1) weekly messages in which that participant's statin adherence was compared to that of other participants (comparison), 2) weekly summaries of that participant's statin adherence (summary), or 3) control. In SUPPORT, each participant identified another person (the Medication Adherence Partner [MAP]) to receive reports about that participant's adherence, and was randomized to 1) daily reports to MAP, 2) weekly reports to MAP, 3) reports to MAP only if dose was missed, or 4) control. MAIN OUTCOMES MEASURE: Adherence measured by pill bottle. KEY RESULTS: Among 45,000 health plan members contacted by mail, <1% joined the trial. Participants had low baseline MPRs (median = 60%, IQR 41-72%) but high pill-bottle adherence (90% in PROMOTE, 92% in SUPPORT) during the trial. In PROMOTE (n = 201) and SUPPORT (n = 200), no intervention demonstrated significantly better adherence vs. CONTROL: In a subgroup of PROMOTE participants with the lowest pre-study MPR, pill-bottle-measured adherence in the comparison arm (89%) was higher than the control (86%) and summary (76%) arms, but differences were non-significant (p = 0.10). CONCLUSIONS: Interventions based on social forces did not improve medication adherence vs. control over a 3-month period. Given the low percentage of invited individuals who enrolled, the studies may have attracted participants who required little encouragement to improve adherence other than study participation.

Functional status, time to transplantation, and survival benefit of kidney transplantation among wait-listed candidates.

BACKGROUND: In the context of an aging end-stage renal disease population with multiple comorbid conditions, transplantation professionals face challenges in evaluating the global health of patients awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis. STUDY DESIGN: Retrospective cohort study of wait-listed patients using data for functional status from a national dialysis provider linked to United Network for Organ Sharing registry data. SETTING & PARTICIPANTS: Adult kidney transplantation candidates added to the waiting list between 2000 and 2006. PREDICTOR: Physical Functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey, analyzed as a time-varying covariate. OUTCOMES: Kidney transplantation; survival benefit of transplantation versus remaining wait-listed. MEASUREMENTS: We used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplantation status was modeled as a time-varying covariate. RESULTS: The cohort comprised 19,242 kidney transplantation candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline Physical Functioning score quartile were more likely to be inactivated (adjusted HR vs highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse Physical Functioning score was associated with shorter 3-year survival (84% vs 92% for the lowest vs highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile. LIMITATIONS: Functional status is self-reported. CONCLUSIONS: Even patients with low function appear to live longer with kidney transplantation versus dialysis. For wait-listed patients, global health measures such as functional status may be more useful in counseling patients about the probability of transplantation than in identifying who will derive a survival benefit from it.

A Pilot Randomized Trial of Financial Incentives or Coaching to Lower Serum Phosphorus in Dialysis Patients.

OBJECTIVE: Among chronic hemodialysis patients, hyperphosphatemia is common and associated with mortality. Behavioral economics and complementary behavior-change theories may offer valuable approaches to achieving phosphorus (PO4) control. The aim was to determine feasibility of implementing financial incentives and structured coaching to improve PO4 in the hemodialysis setting. DESIGN AND METHODS: This pilot randomized controlled trial was conducted in 3 urban dialysis units for 10 weeks among 36 adults with elevated serum PO4 (median >5.5 mg/dL over 3 months). INTERVENTIONS: Twelve participants each were randomized to: (1) financial incentives for lowering PO4, (2) coaching about dietary and medication adherence, or (3) usual care. PO4 was measured during routine clinic operations. Each incentives arm participant received the equivalent of $1.50/day if the PO4 was ≤5.5 mg/dL or >5.5 mg/dL but decreased ≥0.5 mg/dL since the prior measurement. The coach was instructed to contact coaching arm participants at least 3 times per week. MAIN OUTCOME MEASURES: The outcome measures included: (1) enrollment rate, (2) dropout rate, and (3) change in PO4 from beginning to end of 10-week intervention period. RESULTS: Of 66 eligible patients, 36 (55%) enrolled. Median age was 53 years, 83% were black race, and 78% were male. Median baseline PO4 was 6.0 (interquartile range 5.6, 7.5). Using stratified generalized estimation equation analyses, the monthly decline in PO4 was -0.32 mg/dL (95% CI -0.60, -0.04) in the incentives arm, -0.40 mg/dL (-0.60, -0.20) in the coaching arm, and -0.24 mg/dL (-0.60, 0.08) in the usual care arm. No patients dropped out. All intervention arm participants expressed interest in receiving similar support in the future. CONCLUSIONS: This pilot trial demonstrated good feasibility in enrollment and implementation of novel behavioral health strategies to reduce PO4 in dialysis patients.

Effect of Financial Incentives for Process, Outcomes, or Both on Cholesterol Level Change: A Randomized Clinical Trial.

Importance: Financial incentives may improve health behaviors. It is unknown whether incentives are more effective if they target a key process (eg, medication adherence), an outcome (eg, low-density lipoprotein cholesterol [LDL-C] levels), or both. Objective: To determine whether financial incentives awarded daily for process (adherence to statins), awarded quarterly for outcomes (personalized LDL-C level targets), or awarded for process plus outcomes induce reductions in LDL-C levels compared with control. Design, Setting, and Participants: A randomized clinical trial was conducted from February 12, 2015, to October 3, 2018; data analysis was performed from October 4, 2018, to May 27, 2021, at the University of Pennsylvania Health System, Philadelphia. Participants included 764 adults with an active statin prescription, elevated risk of atherosclerotic cardiovascular disease, suboptimal LDL-C level, and evidence of imperfect adherence to statin medication. Interventions: Interventions lasted 12 months. All participants received a smart pill bottle to measure adherence and underwent LDL-C measurement every 3 months. In the process group, daily financial incentives were awarded for statin adherence. In the outcomes group, participants received incentives for achieving or sustaining at least a quarterly 10-mg/dL LDL-C level reduction. The process plus outcomes group participants were eligible for incentives split between statin adherence and quarterly LDL-C level targets. Main Outcomes and Measures: Change in LDL-C level from baseline to 12 months, determined using intention-to-treat analysis. Results: Of the 764 participants, 390 were women (51.2%); mean (SD) age was 62.4 (10.0) years, 310 (40.6%) had diabetes, 298 (39.0%) had hypertension, and mean (SD) baseline LDL-C level was 138.8 (37.6) mg/dL. Mean LDL-C level reductions from baseline to 12 months were -36.9 mg/dL (95% CI, -42.0 to -31.9 mg/dL) among control participants, -40.0 mg/dL (95% CI, -44.7 to -35.4 mg/dL) among process participants, -41.6 mg/dL (95% CI, -46.3 to -37.0 mg/dL) among outcomes participants, and -42.8 mg/dL (95% CI, -47.4 to -38.1 mg/dL) among process plus outcomes participants. In exploratory analysis among participants with diabetes and hypertension, no spillover effects of incentives were detected compared with the control group on hemoglobin A1c level and blood pressure over 12 months. Conclusions and Relevance: In this randomized clinical trial, process-, outcomes-, or process plus outcomes-based financial incentives did not improve LDL-C levels vs control. Trial Registration: ClinicalTrials.gov Identifier: NCT02246959.

A Randomized Trial of Theory-Informed Appeals for Organ Donor Registration Using Internet Advertisements.

INTRODUCTION: Many people do not register as organ donors. We developed 5 different brief appeals for organ donation that were disseminated online. The content was informed by theories of behavior change and studies of the specific cognitive barriers to organ donor registration. METHODS: One message was a persuasive narrative about a transplant recipient. Another message promoted the idea that organ donor registration is a social norm. The knowledge-based message communicated that 1 donor could improve the lives of 50 people. The message on reciprocity offered a free organ donation wristband, whether or not the participant registered as a donor. The message on control simply encouraged organ donation. Using Google AdWords, the messages were deployed randomly as banners of different sizes on diverse online sites and carried a link to an organ donor registration site. We measured clicks, page visits, and organ donor registrations. RESULTS: There were 5,156,048 impressions and 25,001 total clicks, a click-through rate of 0.49%. The messages on control and reciprocity both had the highest click-through rates of 0.51%. A total of 152 unique individuals requested wristbands and there were 52 total organ donor registration events. The message on reciprocity had the highest number of organ donor registrations (n = 18). CONCLUSION: Online organ donation messages rapidly generated substantial attention through clicks, but no message led to a meaningful number of organ donor registrations. Future research may focus on effectively capturing the attention of viewers through social networks or other convenient online venues with less competition for attention than Internet banners.

Race, Risk, and Willingness of End-Stage Renal Disease Patients Without Hepatitis C Virus to Accept an HCV-Infected Kidney Transplant.

BACKGROUND: Despite effective antiviral treatment, hundreds of kidneys from deceased donors with hepatitis C virus (HCV) are discarded annually. Little is known about the determinants of willingness to accept HCV-infected kidneys among HCV-negative patients. METHODS: At 2 centers, 189 patients undergoing initial or reevaluation for transplant made 12 hypothetical decisions about accepting HCV-infected kidneys in which we systematically varied expected HCV cure rate, allograft quality, and wait time for an uninfected kidney. RESULTS: Only 29% of the participants would accept an HCV-infected kidney under all scenarios, whereas 53% accepted some offers and rejected others, and 18% rejected all HCV-infected kidneys. Higher cure rate (odds ratio [OR], 3.49; 95% confidence interval [CI], 2.33-5.24 for 95% vs 75% probability of HCV cure), younger donor (OR, 2.34; 95% CI, 1.91-2.88 for a 20-year-old vs a 60-year-old hypertensive donor), and longer wait for an uninfected kidney (OR, 1.43; 95% CI, 1.22-1.67 for 5 years vs 2 years) were associated with greater willingness to accept an HCV-infected kidney. Black race modified the effect of HCV cure rate, such that willingness to accept a kidney increased less for blacks versus whites as the cure rate improved. Patients older than 60 years and prior kidney recipients showed greater willingness to accept an HCV-infected organ. CONCLUSIONS: Most patients will consider an HCV-infected kidney in some situations. Future trials using HCV-infected kidneys may enhance enrollment by targeting older patients and prior transplant recipients, but centers should anticipate that black patients' acceptance of HCV-infected kidneys will be reduced compared with white patients.

Measures of Global Health Status on Dialysis Signal Early Rehospitalization Risk after Kidney Transplantation.

BACKGROUND: Early rehospitalization (<30 days) after discharge from kidney transplantation (KT) is associated with poor outcomes. We explored summary metrics of pre-transplant health status that may improve the identification of KT recipients at risk for early rehospitalization and mortality after transplant. MATERIALS AND METHODS: We performed a retrospective cohort study of 8,870 adult (≥ 18 years) patients on hemodialysis who received KT between 2000 and 2010 at United States transplant centers. We linked Medicare data to United Network for Organ Sharing data and data from a national dialysis provider to examine pre-KT (1) Elixhauser Comorbidity Index, (2) physical function (PF) measured by the Short Form 36 Health Survey, and (3) the number of hospitalizations during the 12 months before KT as potential predictors of early rehospitalization after KT. We also explored whether these metrics are confounders of the known association between early rehospitalization and post-transplant mortality. RESULTS: The median age was 52 years (interquartile range [IQR] 41, 60) and 63% were male. 29% were rehospitalized in <30 days, and 20% died during a median follow-up time of five years (IQR 3.6-6.5). In a multivariable logistic model, kidney recipients with more pre-KT Elixhauser comorbidities (adjusted odds ratio [aOR] 1.09 per comorbidity, 95% Confidence Interval [CI] 1.07-1.11), the poorest pre-KT PF (aOR 1.24, 95% CI 1.08-1.43), or >1 pre-KT hospitalizations (aOR 1.32, 95% CI 1.17-1.49) were more likely to be rehospitalized. All three health status metrics and early rehospitalization were independently associated with post-KT mortality in a multivariable Cox model (adjusted hazard ratio for rehospitalization: 1.41, 95% CI 1.28-1.56). CONCLUSIONS: Pre-transplant metrics of health status, measured by dialysis providers or administrative data, are independently associated with early rehospitalization and mortality risk after KT. Transplant providers may consider utilizing metrics of pre-KT global health status as early signals of vulnerability when transitioning care after KT.

Functional status and survival after kidney transplantation.

BACKGROUND: Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. METHODS: We linked United Network for Organ Sharing registry data about posttransplantation survival with pretransplantation functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for 3-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. RESULTS: The cohort comprised 10,875 kidney transplant recipients with a mean age of 50 years; 14% were ≥65. Differences in 3-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients ≥65 years. In multivariable Cox regression, worse PF was associated with higher mortality (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions between PF and age were nonsignificant. We estimated that 11% fewer deaths would occur if kidney transplant recipients with the lowest functional status experienced modest improvements in function. CONCLUSIONS: Across a wide age range, functional status was an independent predictor of posttransplantation survival. Functional status assessment may be a useful tool with which to counsel patients about posttransplantation outcomes.