Ecological Momentary Assessment of Midlife Adults’ Daily Stress: Protocol for the Stress Reports in Variable Environments (STRIVE) App Study

Background Daily stressors are associated with cognitive decline and increased risk of heart disease, depression, and other debilitating chronic illnesses in midlife adults. Daily stressors tend to occur at home or at work and are more frequent in urban versus rural settings. Conversely, spending time in natural environments such as parks or forests, or even viewing nature-themed images in a lab setting, is associated with lower levels of perceived stress and is hypothesized to be a strong stress “buffer,” reducing perceived stress even after leaving the natural setting. However, many studies of daily stress have not captured environmental contexts and relied on end-of-day recall instead of in-the-moment data capture. With new technology, these limitations can be addressed to enhance knowledge of the daily stress experience. Objective We propose to use our novel custom-built Stress Reports in Variable Environments (STRIVE) ecological momentary assessment mobile phone app to measure the experience of daily stress of midlife adults in free-living conditions. Using our app to capture data in real time will allow us to determine (1) where and when daily stress occurs for midlife adults, (2) whether midlife adults’ daily stressors are linked to certain elements of the built and natural environment, and (3) how ecological momentary assessment measurement of daily stress is similar to and different from a modified version of the popular Daily Inventory of Stressful Events measurement tool that captures end-of-day stress reports (used in the Midlife in the United States [MIDUS] survey). Methods We will enroll a total of 150 midlife adults living in greater Indianapolis, Indiana, in this study on a rolling basis for 3-week periods. As those in underrepresented minority groups and low-income areas have previously been found to experience greater levels of stress, we will use stratified sampling to ensure that half of our study sample is composed of underrepresented minorities (eg, Black, American Indian, Hispanic, or Native Pacific Islanders) and approximately one-third of our sample falls within low-, middle-, and high-income brackets. Results This project is funded by the National Institute on Aging from December 2022 to November 2024. Participant enrollment began in August 2023 and is expected to finish in July 2024. Data will be spatiotemporally analyzed to determine where and when stress occurs for midlife adults. Pictures of stressful environments will be qualitatively analyzed to determine the common elements of stressful environments. Data collected by the STRIVE app will be compared with retrospective Daily Inventory of Stressful Events data. Conclusions Completing this study will expand our understanding of midlife adults’ experience of stress in free-living conditions and pave the way for data-driven individual and community-based intervention designs to promote health and well-being in midlife adults. International Registered Report Identifier (IRRID) DERR1-10.2196/51845

incorporate environmental stress triggers, and community-based interventions designed to eliminate environmental stressors that are commonly experienced by mid-life adults (e.g., congested areas).

PUBLIC HEALTH RELEVANCE:
The experience of daily stressors can accelerate cognitive decline and increase the risk of heart disease, depression, and other debilitating chronic illnesses -especially for those who are in underrepresented minority groups or live in low-income areas.In this project, we measure the daily stressors of mid-life (aged 50-64) adults using mobile phones, which allows us to better understand where and how stressors happen as people go about their daily lives.This knowledge can be used to develop community or psychological interventions to address environmental stressors and promote healthy aging.

CRITIQUE 1
Significance: 2 Investigator(s): 1 Innovation: 1 Approach: 2 Environment: 3 Overall Impact: This resubmission seeks to determine where and when daily stress occurs for mid-life adults in the built and natural environment, which environmental factors play a role in stress, and how certain groups (e.g., minorities, low income) are disparately impacted by the environments in which they live among 300 mid-life (age 50-64) adults from the greater Indianapolis area of Indiana.The longterm goal of proposed work is advancing the understanding of the environmental features that encourage or interfere with healthy aging to inform potential interventions aimed at removing environmental stressors and promoting activities in healthy environments.The significance of the topic and innovative combination of measurement tools are distinct strengths of the application.The research team is well-qualified, and appropriate analytical methodology has been proposed to achieve the aims of the study.However, reviewers noted weaknesses that lowered enthusiasm for the proposal, including a weak physical activity measure; lack of measurement for substance use; lack of generalizability; data collection at work; lack of data about validity and reliability of stress measures; potential safety issues related to taking photos; absence of documented community-based support; lack of income based sampling; and no clear plan for ensuring that most salient indicators of stress would lead to intervention.While investigators responded to a number of concerns, there are weaknesses that have not been addressed, so even with the significant and timely nature of the proposal, its potential to generate robust and responsive evidence that adds substantially to the field is not completely clear.

Strengths
• In the United States, mid-life adults are staying in the workforce longer and are engaging in higher levels of physical activity than previous generations, potentially extending their interactions with elements of the built and natural environments that influence their experience of daily stress.
• The experience of daily stress can be detrimental to the health of mid-life adults, and research has shown that stress can accelerate cognitive decline and increase the risk of heart disease, depression, and other debilitating chronic illnesses.
• Stress has been particularly associated with places like home, work, and urban environments.
• Natural environments such as parks or the woods are associated with reduced perceived stress, and spending time in natural environments can create a stress 'buffer', reducing overall stress arousal even after leaving.
• Neighborhoods with high poverty rates and higher proportions of racial or ethnic minorities have less access to green space and higher exposure to stressful environmental elements like abandoned buildings and crime.
• Knowledge about where and when daily stress occurs can be used by community planners to address areas in the built and natural environment where stress happens most often, community organizations to provide support during high stress time periods within those locations, healthcare providers to make recommendations for healthy behaviors, and mid-life adults to make decisions about their movements in the built and natural environment to reduce daily stress.
• Little is known about the real life experience of daily stress, as past research has collected data primarily using end-of-day recall, which is subject to recall error and bias.
• Lack of naturalistic, real-world stress data from mid-life adults, which limits the ability to use stress research to inform health recommendations, treatments, or interventions.
• This project is expected to yield a more comprehensive understanding of (1) where and when daily stress happens for mid-life adults and (2) whether daily stressors are attributable to certain elements of the built and natural environment.
• Preliminary analysis of data collected in two pilot studies indicate that real time method of measuring daily stress results in greater capture of daily stressors.

Weaknesses
• Indiana sample is not representative of the adult US population.

Strengths
• PI has experience implementing ecological momentary assessment of stress using mobile and wearable technology in the context of tourism.
• PI has overseen two preliminary studies, one in a tourism context, and one that identically matches currently proposed methods.
• Study team has complementary expertise in physical activity and quality-of-life outcomes; sociotechnical systems and mechanisms to support health and wellbeing and reduce health disparity of marginalized and underserved populations; a range of methodologies, including labbased experimental studies, daily diary studies, longitudinal observational studies, and controlled intervention trials to examine how stress in a variety of forms influences emotion, cognition, and cellular functioning; epidemiologic, statistical, and geospatial modeling techniques; and extensive experience in designing and conducting clinical and public health studies focusing on various adverse outcomes as a function of where individuals live, specifically aspects of neighborhood-based research using advanced epidemiological methods (e.g., bias correction, propensity scores), a geographic information system (GIS), and spatial statistics.
• Blossoming funding and publication records.
• None noted by reviewer.

Strengths
• Innovative combination of measurement tools, including a smartphone based ecological momentary assessment app, ambulatory ECG monitor, and mixed methods analysis including spatiotemporal models and qualitative thematic analysis.
• Advances in mobile and wearable technology now allows for capturing in the moment accounts of stress, heart rate variability, and geospatial location simultaneously.
• Capturing these data in real time can help reduce recall bias and allow for a better understanding of where stress occurs in the built and natural environment.In the moment measurements of daily stress in free-living conditions also allows examination of intraday stress, which is unable to be captured by popular daily recall methods of measuring daily stress.
Capturing in the moment stress data will also allow investigators to attribute stressors directly to elements of the environment in which they occur, rather than other variables such as participant activities.

Weaknesses
• None noted by reviewer.

Strengths
• Multi-method, transdisciplinary approach to measuring the psychological (in the moment selfreports) and physiological (heart rate variability (HRV)) experience of stress in free-living conditions for mid-life adults.
• Use of a custom-built smartphone-based ecological momentary assessment (EMA) app and ambulatory electrocardiogram (ECG) recorder.
• EMA app passively collects global positioning system (GPS) coordinates of research participants several times per minute in addition to participant self-reports of daily stressors, including subjective severity.
• Ambulatory ECG monitor records heart rate 24-hours per day at 1ms resolution.
• Spatiotemporal analysis of reported stressful events and HRV data will allow investigators to determine where research participants are (and aren't) when they experience stress in the built and natural environment.
• Participant reports of daily stressors via EMA app will include a short description of the stressful experience and a picture of the stressful environment for context, allowing for qualitative thematic analysis of text-and image-based stressor data and providing rich detail in understanding of stressors and the role the environment played in stressful experiences.
• 300 mid-life adults will be recruited to participate in the study for one week on a rolling basis.
• Purposive sampling to ensure a minimum of half of research participants are members of minority groups. Weaknesses • No conceptual model presented that is matched with the selection of variables to guide assessment and evaluation in the study.

Strengths
• Appear to have necessary resources at respective institutions to carry out proposed work • Leverages lab that designs, prototypes, and deploys novel personal health informatics devices, interfaces, and platforms to support people with physical, developmental, and mental conditions. •

Biohazards:
Not Applicable (No Biohazards) Resubmission: • Investigators have substituted a chest worn ambulatory electrocardiogram (ECG) monitor for a Polar Unite smartwatch in the proposal.The Polar watch is a much less invasive and more practical tool for measuring ambulatory heart rate (via photoplethysmography (PPG)) and activity level (via accelerometer).The HR and activity level measurements collected via the Polar smartwatch will be incorporated into the spatiotemporal model as covariates.
• Added Aim 3, which compares number of stressors, stressor type, and subjective severity of stressors between STRIVE and the DISE.This analysis will show how stressor data collected by these two tools are similar and different.
• Secured a letter of support from the Indiana Clinical and Translational Sciences Institute (CTSI) committing their recruitment concierge services team will aid in the recruitment of study participants via the All IN for Health volunteer registry and community partnerships.
• Added a table (Table 2) that summarizes all study variables that will be collected in the pre-test survey, real time, and end of day recall.
• Added the details of IRB approved protocol with instructions for reporting stressors in potentially dangerous situations and instructions for taking pictures of stressful environments.
• Now include pretest measures of childhood stress (ACES) as well as other common stressors (e.g., financial strain) to account for these stressors.
• Expanded the data collection period to three-weeks (2 weeks for each measurement tool with 1 week of overlap) to obtain a more robust sample of stressors.
• Pre-test survey now includes some measures of interpersonal stress (e.g., social provisions scale).

Resource Sharing Plans:
Acceptable Budget and Period of Support:

CRITIQUE 2
Significance: 3 Investigator(s): 2 Innovation: 2 Approach: 3 Environment: 2 Overall Impact: This resubmission R21 application is from a strong interdisciplinary group of investigators that seeks to measure stress in real time and space, and to tie these measures to the places in the built and natural environment in which they occur.The methods to be used are innovative.
The team has provided data to support the methods.The topic is important because daily stress contributes to physical and mental health outcomes.There is potential to develop targeted interventions and/or treatments because the data provides information in real time and space.The investigative team addressed many (if not all) of the minor to moderate weaknesses noted in the first submission, including a new measure of objective physical activity, survey data on substance use and abuse, and inclusion of a NIA recommended tool for measuring daily stressors.Overall, the proposed research will provide important data on novel methods for measuring stress in real time and space, and such data can lead to actionable ways of handling stress encountered in daily life in the future.

Strengths
• Spatiotemporal data collection that can lead to actionable recommendations, treatments, or interventions.
• Plans to enhance recruitment of populations particularly exposed to stress.

Weaknesses
• The previous lack of perceived and/or actual stress measures in early life has largely been addressed, although the measures included are imperfect and reflect primarily adverse childhood events and current financial strain.(minor weakness)

Strengths
• PI is an ESI with experience specific to the application's focus (stress in the built and natural environment) as documented through a few publications and 3 grants.
• Co-Is provide additional expertise.

Weaknesses
• None noted by reviewer.

Strengths
• Subjective and objective measures of stress where and when they occur in daily life.
• Use of tools to capture and analyze data within a spatiotemporal framework.

Weaknesses
• The DISE tool is an imperfect "gold (alloy) standard" of daily stress, but it is replicable.(minor weakness).

Strengths
• Comprehensive list of confounding variables that will be measured and included in statistical models.

Weaknesses
• The need for participants to use their smartphones to report daily stressors in the moment is itself a stressor -this could lead to "fatigue" in that participants may not wish to report all stressors they encounter to reduce burden on themselves.(minor weakness) • Still not clear what land cover use data ISDP provides and what variables will be created from such data -will this be used for a measure of green space akin to NDVI? -noted on page 51 that this data "will permit us to determine characteristics of the built/natural environment such as tree canopy cover, parks, residential green spaces and designated land uses ……. for each timestamp location."(minor weakness) JORDAN, E

Strengths
• More than adequate for the proposed research.

Weaknesses
• None noted by reviewer.

Protections for Human Subjects:
Unacceptable Risks and/or Adequate Protections • Participants should be made aware that knowledge of their geolocation is a potential risk (i.e., confidentiality) and should be provided the opportunity to turn off instrumentation when they are in a place they perceive as sensitive (this is similar to items describing guidelines about when it is and is not ok to take a picture of stressful environments).

Biohazards:
Not Applicable (No Biohazards) Resubmission: • The investigators provide a detailed explanation of changes to the A1 proposal.Importantly, they have decided to do away with an HRV measure and instead include a tool to measure HR and activity levels continuously.Other major changes include inclusion of a reliable tool for measuring stress (an "alloy" standard) and improved sampling and recruitment strategies.

Resource Sharing Plans:
Acceptable Budget and Period of Support: Recommend as Requested Overall Impact: This proposal addresses a very significant issue in the measurement of daily stressors with a focus on spatial-temporal correlates.Overall impact is moderately high because the research is likely to provide evidence of the validity and feasibility of a measurement tool for improved understanding of contextual mechanisms linked to stress and stress-related health outcomes in mid-life adults.The project is innovative, because it provides evidence for an improved measurement technique that be applied to interventions in this population.The investigative team has appropriate and complementary skills and the environment is excellent.The approach has some very strong aspects such as stratified sampling and excellent plan for recruiting.Most of the weaknesses were minor.However, one weakness created some concern.The weakness was lack of evidence for the team's plan and support for triangulating physiological stress with psychological stress.The problem with this is that they do not provide hypotheses or analyses related to this and the investigator identified with this expertise is not included in project (e.g., no biosketch).Additionally, the unprecedented plan for longterm monitoring of participants and management of large quantities of data not credibly addressed.In conclusion, despite the weakness in the approach, the potential overall impact of this project remains high because it will advance understanding of the mechanisms underlying the relationship between neighborhood context and stress-related health issues and test new methods that will be useful in both epidemiological and translational research areas.

Strengths
• Use of STRIVE to identify daily stressors in the moment and place they occur connected with environmental context including crime, greenspace, and landuse is an exciting opportunity to better characterize exposure and identify mechanisms for stress-related health outcomes.
• Preliminary data support the feasibility and value of using the STRIVE app; proposed project will add information about the value added compared to existing end of day survey.
• Research credibly links the anticipated study findings regarding evidence of daily stressors that are relevant for this population to the development of evidence-based individual and community interventions to address health and well-being in mid-life adults.

Weaknesses
• Proposal provides no convincing evidence that majority of daily stress related to environmental exposure.
• Although proposal identifies importance of work for mid-life adults, aims do not directly address relevant contextual work-related information (e.g., stress occurring inside workplace).

Investigator(s):
Strengths CIHB JORDAN, E • Investigators have complementary expertise needed to conduct the proposed project (measurement of stress, EMA, psychological stress, activity/heart rate, GIS.

Weaknesses
• Schootman provides expertise to integrate heart rate and activity levels into spatiotemporal analyses and interpretation for Aim 1 but no biosketch is included.
• Plan for coordination of transdisciplinary team not clear.

Strengths
• Use of EMA to more effectively link stress to environmental exposures over time is innovative.

Weaknesses
• Integration of passive data collection (of heart rate and activity) when examining the impact of stress on well-being is potentially innovative but this aspect is not well developed (not clear that project has aims, methods to fully contribute).

Strengths
• Stratified sampling approach ensures adequate representation by SES and race/ethnicity.• Well designed protocols.
• Analyses appropriate to address aims.

Weaknesses
• Minor concern regarding participant burden given the long study period and intensive requirements has not been adequately addressed and may lead to unanticipated drop-out.
• Moderate concern regarding feasibility/process of data management for unprecedented amounts of data collected in this study not adequately addressed.
• Moderate concern regarding analyses/hypotheses related to triangulation of physiological stress with psychological stress not provided thus limits the likely significance of the findings.
• Minor concern regarding Workplace identified but not directly addressed in terms of reporting/capturing information.

Strengths
• Resources, facilities, and equipment appropriate for the needs of the proposed project including management and analysis of data generated from EMA.
Weaknesses CIHB JORDAN, E • None noted by reviewer.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections

• Acceptable
Inclusion Plans: • Sex/Gender: Distribution justified scientifically • Responsive to prior comments.Specifically, changed stratified sampling plan to ensure adequate variability in participants, added third aim to compare EMA tool (STRIVE) to recommended daily measure (DISE), substituted less invasive data collection for heart rate and activity, and provided additional information regarding feasibility of recruitment.

Budget and Period of Support:
Budget Modifications Recommended (in amount/time) Recommended budget modifications or possible overlap identified: • BSC does not identify data management as a responsibility in this project.Research assistants only in Y1 (relatively limited amount of time given the large population and need for recruitment/data collection; no research assistants in Y2 to provide support for data management.Schootman not identified in budget justification.

THE FOLLOWING SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE, OR REVIEWERS' WRITTEN CRITIQUES, ON THE FOLLOWING ISSUES:
PROTECTION OF HUMAN SUBJECTS: UNACCEPTABLE.The protection of human subjects from research risks is unacceptable.See Reviewer 2 comments.This needs to be addressed.

INCLUSION OF WOMEN PLAN: ACCEPTABLE
Footnotes for 1 R21 AG077333-01A1; PI Name: Jordan, Evan + Derived from the range of percentile values calculated for the study section that reviewed this application.
NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-18-197 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-197.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.
Investigative team has developed relationships with local public health organizations focused on minority populations (e.g., Minority Health Coalition of Marion County) who have committed to aid in recruitment of those in minority groups.
Weaknesses• Investigators report that several local public health organizations have committed to share recruitment via social media, but there are NO community-based letters of support included.Protections for HumanSubjects: Acceptable Risks and/or Adequate Protections Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Acceptable Inclusion Plans: • Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • Inclusion/Exclusion Based on Age: Distribution justified scientifically Vertebrate Animals: Not Applicable (No Vertebrate Animals)