Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.

Introduction: Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of "informativeness," highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Methods and Results: Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. Conclusions: We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Embracing Advanced Methodology to Improve Population Health

In 2004, we asked David Murray1,2 and Allan Donner,3 two pioneers in the development and application of group or cluster randomized trials, to provide extensive primers on their design, application, and analysis, and invited them to help keep these tools in our analytic toolbox by providing methodological updates in 2017.4,5 In 2018, we embraced the notion of returning "cause" to our public health vocabulary, and employing causal inference methods to our data when appropriate. METHODOLOGICAL ADVANCES First, Wang and Chakraborty (p. 49) present an outstanding review of a method that overcomes some of the downsides oftraditional randomized controlled trials, which often tend to compare one novel treatment to standard or usual care, where participants remain in their assigned treatment groups over the life of the trial. [...]it can help, in real time, predict the number of tests that will be needed to better inform the supply chain needs and can incorporate the often-dynamic parameters of a pandemic rather than relying on fixed and perhaps outdated inputs.

Implementing DASH-Aligned Meals and Self-Measured Blood Pressure to Reduce Hypertension at Senior Centers: A RE-AIM Analysis.

Low-income, minority seniors face high rates of hypertension that increase cardiovascular risk. Senior centers offer services, including congregate meals, that can be a valuable platform to reach older adults in underserved communities. We implemented two evidence-based interventions not previously tested in this setting: DASH-aligned congregate meals and Self-Measured Blood Pressure (SMBP), to lower blood pressure (BP) at two senior centers serving low-income, racially diverse communities. The study enrolled congregate meal program participants, provided training and support for SMPB, and nutrition and BP education. DASH-aligned meals delivered 40% (lunch) or 70% (breakfast and lunch) of DASH requirements/day. Primary outcomes were change in BP, and BP control, at Month 1. Implementation data collected included client characteristics, menu fidelity, meal attendance, SMBP adherence, meal satisfaction, input from partner organizations and stakeholders, effort, and food costs. We used the RE-AIM framework to analyze implementation. Study Reach included 94 older, racially diverse participants reflecting neighborhood characteristics. Effectiveness: change in systolic BP at Month 1 trended towards significance (-4 mmHg, p = 0.07); change in SMBP reached significance at Month 6 (-6.9 mmHg, p = 0.004). We leveraged existing community-academic partnerships, leading to Adoption at both target sites. The COVID pandemic interrupted Implementation and Maintenance and may have attenuated BP effectiveness. DASH meals served were largely aligned with planned menus. Meal attendance remained consistent; meal satisfaction was high. Food costs increased by 10%. This RE-AIM analysis highlights the acceptability, feasibility, and fidelity of this DASH/SMBP health intervention to lower BP at senior centers. It encourages future research and offers important lessons for organizations delivering services to older adults and addressing cardiovascular risk among vulnerable populations.

Implementing DASH-aligned Congregate Meals and Self-Measured Blood Pressure in two senior centers: An open label study.

BACKGROUND AND AIMS: Cardiovascular Disease (CVD) poses significant health risks for seniors, especially among low-income and minority communities. Senior centers offer multiple services. We tested whether implementing two evidence-based interventions- DASH-aligned meals provided through an existing congregate meal program, and support for home Self-Measured Blood Pressure (SMBP) monitoring-lowers blood pressure among participants at two senior centers serving low-income, racially diverse communities. METHODS AND RESULTS: Open-label study, enrolling clients aged ≥60, eating ≥4 meals/week at two NYC senior centers. Participants received DASH-aligned congregate meals, and training in nutrition, BP management education, and personal SMBP device. Co-Primary outcomes: a) change in systolic BP measured by independent health professionals, and b) change in percent with "controlled BP" (Eighth Joint National Committee (JNC-8) Guidelines), at Month 1 compared to Baseline. SECONDARY OUTCOMES: Changes in BP at Months 3 and 5/6 (last measure). We enrolled 94 participants; COVID closures interrupted implementation mid-study. Mean systolic BP at Month-1 changed by -4.41 mmHg (n = 61 p = 0.07) compared to Baseline. Participants with controlled BP increased (15.7%) at Month 1. Change in mean BP at Month 1 was significantly correlated with BMI (p = 0.02), age (p = 0.04), and baseline BP (p < 0.001). Mean systolic SMBP changed by -6.9 mmHg (p = 0.004) at Months 5/6. CONCLUSIONS: Implementing an evidence-based multi-component BP-lowering intervention within existing congregate meal programs at senior centers serving minority and low-income communities is feasible, and early findings show promising evidence of effectiveness. This approach to cardiovascular risk reduction should be further tested for widespread adoption and impact. Registered on ClinicalTrials.gov NCT03993808 (June 21st, 2019).

A community-academic partnership to implement DASH diet and social/behavioral interventions in congregate meal settings to reduce hypertension among seniors aging in place

IMPACT: Our implementation model translates two evidence-based nutritional and behavioral interventions to lower blood pressure, into a community-based intervention program for seniors receiving congregate meals. OBJECTIVES/GOALS: The Rockefeller University, Clinical Directors Network, and Carter Burden Network received an Administration for Community Living Nutrition Innovation grant to test whether implementation of DASH-concordant meals and health education programs together lower blood pressure among seniors aging in place. METHODS/STUDY POPULATION: n=200, >60 yr, >4 meals/week at CBN;engagement of seniors/stakeholders in planning and conduct;Advisory Committee to facilitate dissemination;menus aligned with Dietary Approaches to Stop Hypertension (DASH) and NYC Department for the Aging nutritional guidelines;interactive sessions for education in nutrition, BP management, medication adherence. Training in use of automated daily home BP monitors (Omron 20). Validated surveys at M0, M1, M3, M6. Taste preference and cost assessed through Meal Satisfaction (Likert scale) and Plate Waste measures. Primary Outcome: Change in Systolic BP (SBP) at Month 1;change in %BP controlled. Secondary: validated cognitive, behavioral, nutritional measures (SF-12, PQH-2), economics;staff/client satisfaction, trends and significant associations. RESULTS/ANTICIPATED RESULTS: n=94, x2 age =73 +/- 8 years, 65% female, 50% White, 32% Black/African American, 4% Asian, 1% American Indian, Alaskan Native, 13% Other, 32% Latino/a, 43% with income <$20,000. Mean SBP at Baseline was 137.87 +18.8 mmHg (range 98-191). Menus were adapted to provide 20% daily DASH requirements at breakfast, 50% at lunch. Participants attended classes in nutrition and medication management and were provided with and trained to use an automated home BP monitor. Meal satisfaction scores dipped briefly then met or exceed pre-DASH levels. Home BP data was downloaded every 2-4 weeks with social/behavioral support. The COVID-19 closures interfered with BP outcome data collection and meal service ceased. Primary outcome: x2 change in SBP at Month 1 = -4.41 mmHg + 18 (n=61) (p=0.713). Significant associations will be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our community-academic research partnership implemented the DASH diet in congregate-meal settings to address uncontrolled hypertension in seniors. COVID-19 interrupted the study, but encouraging trends were observed that may inform refinement to this community-based health intervention for seniors.

Accounting for the Full Scope of Health Consequences of Policy Decisions Across the Life Course

The sheer scope ofthe consequences of suboptimal diets this study suggests is staggering, even more so when noting that many of the cancers studied were attributable to high consumption of sugar-sweetened beverages and low consumption of whole grains. Efforts to mitigate the spread of COVID-19 have included a wholesale limitation of population mobility, limiting employment for many, and limiting access to routine health care services for many more. An analysis by Brenner (p. 1950) shows how the economic consequences brought about by mobility restrictions related to slowing the spread of COVID-19 in the United States are associated with nearly 200 000 combined deaths in the long term as a result of unemployment and bankruptcies.

The Role of Natural Experiments in Advancing Public Health Science and Practice

From the preamble to the World Health Organization's constitution, which defines health as a "state of complete physical, mental and social well-being and not merely the absence of disease or infirmity,"1 to recent discussions about the aspirations of public health that grapple with the social and economic forces that shape health,2,3 public health aspires to create a world that generates health and the opportunity for all to flourish and reach their potential. There is good evidence that children exposed to air pollution have worse respiratory systems.7 However, that evidence, borne out through a range of observational studies, has limited potential to influence policy that is specifically about coal-fired power plants related to health improvement. Using wind data, population data, particulate matter 2.5 definitions, and zip code-level rates of emergency department asthma visits for children younger than four years between 2009 and 2017, and applying difference-in-difference methods-a useful analytic approach for such studies-the authors showed that asthma hospitalizations decreased by 12% in zip codes close to the plants that were closed compared with zip codes that were farther away.

The Public Health Penalty of Attending to the Proximal

Clearly, a distal approach to this challenge would be to dismantle a system of incarceration that also doubles as a system of housing people with mental illness and to replace that with a compassionate approach that considers how we tackle the influences that might drive mental illness and how we create systems that can provide support and care for persons with mental illness rather than consign them to a carceral system that, at best, does not tend to their core mental health problems and, at worst, exacerbates them.5 The challenge for public health is that we have a large, and seemingly intractable, system of incarceration as a clear and present reality, and thinking only about undoing such a system exposes us to reasonable charges of unhelpful idealism. Hedden et al. study such systems with the aim of finding whether race/ethnicity is associated with access to jail- and community-based mental health treatment. Given the simple observation that those with more power, privilege, and access are more likely to obtain benefit from any intervention,6 even in, for example, a jail system, it stands to reason that an intervention that targets only the more proximal mechanisms of action will result in exposing underlying inequities, potentially widening health gaps.

Embedding Prevention at the Heart of the US Health Conversation

[...]the pandemic quickly made clear that despite our overwhelming global and national investment in health care and medicine, when the world faces an unprecedented surge in a novel disease, health care systems are simply not up to the challenge and our only viable approach to protect health is preventing the health problem to begin with. LEVERS FOR PREVENTION It is, of course, odd that it took a global pandemic to remind us that prevention of disease is a far preferable approach to promoting the public's health than is treatment once we are already sick. [...]perhaps underlyingthe first and second reasons, is that prevention simply is not at the heart of the US health conversation. Decades of investment in curative care, resulting in the most expensive health care system in the world, has resulted in a US system that privileges treatment, and, perhaps more importantly, treatment is seen as the fundamental purpose of the health system.