Center for Clinical and Translational Science

Introduction
The study of health and illness in populations often begins by observing differences in patterns across person, place, and time.  These differences may provide clues to sources of variation that may reflect not only biological processes, but also underlying inequities in access to resources that some groups experience relative to others. The recent focus on enhancing diversity, equity and inclusion in medical and educational institutions attempts to address these issues of biological diversity, inequities in access to healthcare and the social determinants of health (e.g., safe and attractive housing, recreational facilities,  healthful food, economic stability, and access to education), and inequities in access to diverse medical professionals who provide care.

Clinical research provides a excellent lens with which to examine diversity, equity, and inclusion in access to research, which includes both the composition of the research team, and the “external validity” or generalizability of research findings across the broad range of those at risk of a particular disorder.  This leads to the questions: (1) are the researchers, themselves, representative of the diverse populations they study care for, and (2) are the eligibility criteria and the design of the study optimal to encourage participation by a diverse population of individuals reflecting those who are most affected by the disorder? Thus, the research study itself can become a vehicle for enhancing equity.

Community Engaged Research at The Rockefeller University Center for Clinical and Translational Science
The Community Engaged Research (CEnR) Core at The Rockefeller University Center for Clinical and Translational Science (CCTS), which has been funded by an NIH Clinical and Translational Science Award (CTSA) since 2006, routinely addresses these issues by engaging a broad range of stakeholders in the design, conduct, analysis and dissemination of research conducted by teams formed at the CCTS.  This approach to developing community partnerships has led to a number of interesting and important research and training collaborations, where Rockefeller, in partnership with different types of community organizations, has been able to reach populations that are systematically excluded from research, both as investigators and as research participants.

The CCTS is committed to developing community-academic research partnerships that engage under-represented and marginalized populations into the clinical and translational research enterprise, broadening the scope of questions that are studied by these research collaborations, enhancing the diversity of the participants and the audiences where the results are disseminated, and setting in motion the opportunity to observe the implementation, scale-up, sustainability and public health impact of these research collaborations, while simultaneously discovering the basic mechanisms underlying these sources of variability, a hallmark of Rockefeller research.

In 2006, CCTS partnered with Clinical Directors Network (CDN), a primary care practice-based research network (PBRN), clinician training organization, and an AHRQ-designated Center of Excellence (P30) for practice-based research and learning.  CDN works with Federally Qualified Health Centers (FQHCs) and other primary care safety-net practices across the USA, in partnership with its “Network of Networks,” the CDN N2-PBRN, which includes twelve PBRNs and several other clinical data networks.  These clinical service organizations are often led by practitioners who are master clinicians but may lack the methodologic training to turn their unanswered clinical questions into robust and testable hypotheses. While PBRNs such as CDN are highly successful in addressing epidemiologic and health services-related questions that fall along the community-based and public health (T3/T4) side of the translational research spectrum, they often lack the expertise to ask basic science/mechanistic questions, which are considered the T0/T1/T2side of the translational research spectrum. Herein lies a great opportunity of partnering T0/T1/T2investigators through team science with T3/T4 investigators, thus obtaining the synergy that can come from a full spectrum approach.

Studies of Antibiotic-Resistant Skin Infections
Rockefeller and CDN, in collaboration with several CDN member FQHCs in NYC, Westchester NY and Austin TX, have enrolled patients in several research studies who are receiving care for skin and soft tissue infections (SSTIs) produced by antibiotic-resistant bacteria (MRSA). These infections are challenging for clinicians to manage and very distressing and potentially very serious for patients, especially when they lead to blood-stream infections. These comprised the Community-Associated MRSA Project (CAMP) and included laboratory investigators from Dr. Alex Tomasz’s basic science lab at Rockefeller, CCTS clinical research facilitators, epidemiologists and health services researchers from CDN, practicing clinicians from CDN member FQHCs, and a range of community advisors including a barber (who routinely sees SSTIs on the scalp and neck of customers), a community pharmacist, as well as patients and caregivers who had the lived experience of having infections caused by MRSA.   Together, the research team, which involved two clinical scholar alumnae, Teresa Evering MD MSc (Markowtitz Lab/Aaron Diamond Institute) and Mina Pastagia MD MS (Fischetti Lab), identified and reported on infection-related disparities between study participants who were USA-born, who were more likely to have an SSTI caused by MRSA and those who were born outside of the USA, who were more likely to have an SSTI caused by a similar bacterium that was not resistant to antibiotics. Initial results suggested that participants born in the USA may have had greater lifetime exposures to antibiotics as one potential explanation for the observed difference.

Patients with MRSA infections often have recurrences even after effective treatment and so the group decided collectively to seek funding for a clinical trial to study which factors predict SSTI recurrence, and what interventions can prevent SSTI recurrence and household transmission. The grant proposal was successful and funding for the study came from the Patient Centered Outcomes Research Institute (www.PCORI.org) These questions, spanning basic science through global public health and environmental science, emerged organically as the team explored the implications of the data collected in the initial study.  Ongoing CAMP studies are now examining the clonal diversity of the pathogens, the microbiomes of both the skin and homes where patients live, as well as whether geography and social networks can explain the geospatial distribution of the disease in the communities at risk.

Studies of Cardio-metabolic Risk Among Adolescent Women in NYC
 With funding provided by CCTS pilot studies, the Center for Biomedicine and Nutrition at Rockefeller and the New York Academy of Sciences, CDN and Rockefeller brought together the clinical leaders from a prior NIH-funded cluster randomized clinical trial conducted by CDN to reduce the incidence of low birthweight babies delivered by African American and Latina teenagers in NYC. The clinicians, who were drawn from CDN-member FQHCs and community hospitals, wanted to learn more about their patients’ risk factors. Using data that is generated during routine patient care (“real world data”) to generate a better understanding of disease (“real world evidence”) is an important component in building a “learning healthcare systems.”  The study focused on examining the associations between obesity and cardiometabolic risk factors, including blood pressure, blood lipids and blood glucose, and pregnancy outcomes.  The Rockefeller-CDN-Health Care Team carefully extracted information from the six participating health systems and these data were then analyzed by experts in metabolism, informatics, biostatistics and epidemiology. Together with the practicing clinicians, they demonstrated that obesity correlated with less healthy cardiometabolic parameters, including blood pressure, cholesterol levels, and blood glucose.  A follow-up study extracted data from electronic health records for care provided to similar young women at academic health centers in New York City through the INSIGHT Clinical Research Network.  Analyses conducted by Dana Bielopolski MD PhD, a Clinical Scholar and Carolyn Jiang MS, a biostatistician, demonstrated identical statistically significant trends, but with one strikingly troublesome difference: the impact of obesity on unfavorable cardiometabolic determinants of health was greater for young women receiving health care at FQHCs as compared to those receiving care at academic health centers in NYC.  The difference between these effects is an important measure of health disparities, as the women seen in FQHCs are more likely to be low income and either African American or Latina as compared to women seen in the academic health centers.  Both studies emphasize the importance of “bending the cardiometabolic curve” as the babies born to overweight and obese mothers had higher birthweights, which other studies indicate will make the babies more likely to experience greater cardiometabolic risk as they age. This multigenerational effect probably contributes to the disparities in cardiovascular incidence and mortality rates between blacks and whites reported in national and state data systems.  

Studies of Cardiovascular Risk Factors Among Older Adults
 In a different type of community-academic partnership, CCTS and CDN partnered with the Carter Burden Network (CBN), a community-based provider of senior services, including meals for food-insecure older adults aging in place in NYC.  CBN was interested in partnering with Rockefeller-CDN to design an evaluation study to assess the impact of CBN’s nutritional programs on their participants. After CCTS and CDN staff developed a relationship with the CBN staff and attendees, a CCTS-supported pilot study found high rates of uncontrolled hypertension among the predominately low-income minority food-insecure older adults who come regularly to CBN for congregate meals, food pantry access, health education, and other community services. Uncontrolled hypertension is a major contributor to the disparities in cardiovascular disease and mortality among older adults in communities at risk.  

 

To address this challenging problem the Rockefeller-CDN-CBN team created  novel nutritional programs for community-residing seniors to test two evidence-based interventions to achieve better blood pressure  control: (1) implementing the Dietary Approaches to Stop Hypertension (DASH) diet, which is designed to decrease sodium and saturated fat intake and increase potassium, dietary fiber and mono-unsaturated fat intake, and (2) providing home blood pressure monitors (HBPMs) and training in how to use and record blood pressures taken at home.  Participants had the opportunity to try new foods and new preparations and were invited to provide feedback as the meals were adjusted. COVID-19-related closures of communal meal sites required creativity and so the study changed to providing “grab-and-go” DASH meals.  Preliminary analyses demonstrate a signal of systolic blood pressure reductions that encourage us to think that when optimally employed it will be both effective and sustainable.  

Unique aspects of this partnership included bringing together the scientific and clinical expertise of Rockefeller bionutritionists with the chefs, food preparers and servers at CBN, along with the oversight and approval of city governmental agencies (NYC Department for the Aging and NYC Department of Health and Mental Hygiene).  A parallel mechanistic study funded by a CCTS pilot grant and the National Kidney Foundation, also led by Clinical Scholar Dr. Dana Bielopolski,  involves African American participants with elevated blood pressure who are admitted to the Rockefeller University Hospital, where they are fed the DASH diet, and their blood pressure, kidney-related hormones (renin and aldosterone), electrolytes (sodium, potassium), and urinary exosomes are closely monitored to understand the underlying mechanisms that contribute to the clinical effectiveness of the DASH diet. Thus, this project truly is full spectrum in including basic research and a clinical trial with profound potential implications for public health policy.

Conclusion
These examples of full-spectrum translational research suggest the importance of designing studies that examine health disparities and test implementation strategies from the perspectives of differences across populations (epidemiologic associations) and the underlying basic science which explains these differences (biological mechanisms).  These novel community-academic partnerships bring together Rockefeller, a Clinical and Translational Science Award grantee institution with expertise in basic science, with CDN, a PBRN with expertise in designing and conducting pragmatic clinical trials and observational studies in real-world, community practice-based settings.  These partnerships provide collaborative research and learning opportunities that can enhance diversity, equity, and inclusion by engaging a broader group of stakeholders such as practicing clinicians, other service delivery providers, and patients in the research team, and by conducting studies in settings that reach underserved populations, such as FQHCs and senior centers. The studies profiled above, engage populations across the lifespan, ranging from adolescent women and their babies to seniors aging in place. In this way, we can generate new knowledge that is more broadly representative and inclusive, and implement that new knowledge in diverse settings reaching those most in need.  A great hope for implementation science is the promise of enhancing health equity by designing and testing interventions to reduce and eliminate health disparities in the widest range of possible settings.  We are always looking forward to building new basic science-to-practice research collaborations with those who share our vision and so welcome your suggestions.