Stakeholder engagement infrastructure to support multicenter research networks: Advances from the clinical research networks participating in PCORnet.

Background: The evidence based on the inclusion of patients and other stakeholders as partners in the clinical research process has grown substantially. However, little has been reported on how stakeholders are engaged in the governance of large-scale clinical research networks and the infrastructure used by research networks to support engagement in network-affiliated activities. Objectives: The objective was to document engagement activities and practices emerging from Clinical Research Networks (CRNs) participating in PCORnet, the National Patient-Centered Clinical Research Network, specifically regarding governance and engagement infrastructure. Methods: We conducted an environmental scan of PCORnet CRN engagement structures, assets, and services, focusing on network oversight structures for policy development and strategic decision-making. The scan included assets and services for supporting patient/stakeholder engagement. Data were collected by searching web-based literature and tool repositories, review of CRN Engagement Plans, analysis of previously collected key informant interviews, and CRN-based iterative review of structured worksheets. Results: We identified 87 discrete engagement structures, assets, and services across nine CRNs. All CRNs engage patients/stakeholders in their governance, maintain workgroups and/or staff dedicated to overseeing engagement strategies, and offer one or more services to non-CRN researchers to enhance conducting engaged clinical research. Conclusions: This work provides an important resource for the research community to explore engagement across peers, reflect on progress, consider opportunities to leverage existing infrastructure, and identify new collaborators. It also serves to highlight PCORnet as a resource for non-CRN researchers seeking to efficiently conduct engaged clinical research and a venue for advancing the science of engagement.

Contextual Factors Affecting Implementation of Pediatric Quality Improvement Programs.

OBJECTIVE: Context is a critical determinant of the effectiveness of quality improvement programs. We assessed the role of contextual factors in influencing the efforts of 5 diverse quality improvement projects as part of the Pediatric Quality Measure Program (PQMP) directed by the Agency for Health Care Research and Quality. METHODS: We conducted a mixed methods study of 5 PQMP grantees involving semistructured interviews followed by structured worksheets to identify influential contextual factors. Semistructured interviews and worksheets were completed between August and October 2020. Participants were comprised of PQMP grantee teams (2-4 team members per team for a total of 15 participants). Coding and analysis was based on the Tailored Implementation for Chronic Diseases (TICD) framework. RESULTS: Despite heterogeneity in the process and outcome targets of the PQMP initiatives, professional interactions, incentives and resources, and capacity for organizational change were the domains most commonly identified as influential across the grantees. While social, political, and legal factors was not commonly referenced as an important domain, payer or funder policies (a factor within this domain) was highlighted as one of the most influential factors. Overall, the incentives and resources domain was identified as the most influential. CONCLUSIONS: We found that using a determinant framework, such as the TICD, is valuable in facilitating comparisons across heterogeneous projects, allowing us to identify key contextual factors influencing the implementation of pediatric quality measures across a diverse range of clinical topics and settings. Future quality improvement work should account for this and include resources to support infrastructure development in addition to program implementation.

Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases.

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is "Patient Centered-Research", in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases.

Has dialysis payment reform led to initial racial disparities in anemia and mineral metabolism management?

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.

Intraindividual variation in one-carbon metabolism plasma biomarkers.

Interest in the relationship between one-carbon metabolism (OCM) and carcinogenesis is intensifying, leading to increased use of related biomarkers as measures of exposure. Little is known, however, about the intraindividual variation in these markers and whether or not the use of a single measure is appropriate for assessing exposure-disease relationships in epidemiologic studies. We evaluated the intraindividual variation in plasma concentrations of 19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white participants from the Southern Community Cohort Study who donated blood samples and responded to questionnaires at two time points from 2005 to 2008. Weighted kappa coefficients (κ) were calculated to assess the agreement between quartile assignments based on the repeated measures. Adjusted intraclass correlation coefficients (ICC) were also used to assess the consistency of the two measurements. Most (16/19) OCM biomarkers showed a moderate or better agreement for quartile assignment at the two time points, with only methionine, methionine sulfoxide, and cystathionine having κ ≤ 0.40. The median-adjusted ICC across the 19 biomarkers was 0.60. Reproducibility was highest for flavin mononucleotide [ICC = 0.84, 95% confidence interval (CI), 0.79-0.87] and lowest for methionine and its oxidative product methionine sulfoxide (ICC = 0.22, 95% CI 0.09-0.34; ICC = 0.20, 95% CI 0.07-0.32, respectively). Overall, the intraindividual variation in OCM biomarkers was similar for African Americans and whites and for males and females. Our results suggest that with the exception of methionine and methionine sulfoxide, OCM biomarkers generally have good intraindividual reproducibility and can be considered as reliable exposure measures in epidemiologic studies.

A prospective study of serum 25-hydroxyvitamin d levels and mortality among African Americans and non-African Americans.

The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality. Evidence addressing this hypothesis is limited, especially for African Americans who have a high prevalence of vitamin D insufficiency. The authors conducted a nested case-control study within the prospective Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852 participants who enrolled from 2002 to 2009 and died >12 months postenrollment. Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood collection date. The odds ratios for quartile 1 (<10.18 ng/mL) versus quartile 4 (>21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20, 2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African Americans. The effects were strongest for circulatory disease death, where quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25 (95% CI: 1.33, 7.93) for African Americans and non-African Americans, respectively. The estimated odds of total mortality were minimized in the 25(OH)D range of 35-40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans.

Obesity and all-cause mortality among black adults and white adults.

In recent pooled analyses among whites and Asians, mortality was shown to rise markedly with increasing body mass index (BMI; weight (kg)/height (m)(2)), but much less is known about this association among blacks. This study prospectively examined all-cause mortality in relation to BMI among 22,014 black males, 9,343 white males, 30,810 black females, and 14,447 white females, aged 40-79 years, from the Southern Community Cohort Study, an epidemiologic cohort of largely low-income participants in 12 southeastern US states. Participants enrolled in the cohort from 2002 to 2009 and were followed up to 8.9 years. Hazard ratios and 95% confidence intervals for mortality were obtained from sex- and race-stratified Cox proportional hazards models in association with BMI at cohort entry, adjusting for age, education, income, cigarette smoking, and alcohol consumption. Elevated BMI was associated with increased mortality among whites (hazard ratios for BMI >40 vs. 20-24.9 = 1.37 (95% confidence interval (CI): 1.02, 1.84) and 1.47 (95% CI: 1.15, 1.89) for white males and white females, respectively) but not significantly among blacks (hazard ratios = 1.13 (95% CI: 0.89, 1.43) and 0.87 (95% CI: 0.72, 1.04) for black males and black females, respectively). In this large cohort, obesity in mid-to-late adulthood among blacks was not associated with the same excess mortality risk seen among whites.

A multi-stage approach to maximizing geocoding success in a large population-based cohort study through automated and interactive processes.

To enable spatial analyses within a large, prospective cohort study of nearly 86,000 adults enrolled in a 12-state area in the southeastern United States of America from 2002-2009, a multi-stage geocoding protocol was developed to efficiently maximize the proportion of participants assigned an address level geographic coordinate. Addresses were parsed, cleaned and standardized before applying a combination of automated and interactive geocoding tools. Our full protocol increased the non-Post Office (PO) Box match rate from 74.5% to 97.6%. Overall, we geocoded 99.96% of participant addresses, with only 5.2% at the ZIP code centroid level (2.8% PO Box and 2.3% non-PO Box addresses). One key to reducing the need for interactive geocoding was the use of multiple base maps. Still, addresses in areas with population density <44 persons/km2 were much more likely to require resource-intensive interactive geocoding than those in areas with >920 persons/km2 (odds ratio (OR) = 5.24; 95% confidence interval (CI) = 4.23, 6.49), as were addresses collected from participants during in-person interviews compared with mailed questionnaires (OR = 1.83; 95% CI = 1.59, 2.11). This study demonstrates that population density and address ascertainment method can influence automated geocoding results and that high success in address level geocoding is achievable for large-scale studies covering wide geographical areas.