Notice of Special Interest (NOSI): U.S. Health in the International Perspective
Notice Number:

Key Dates

Release Date:

March 6, 2024

First Available Due Date:
June 05, 2024
Expiration Date:
May 08, 2027

Related Announcements

  • April 3, 2024 - Notice of Pre-Application Webinar for NOT-AG-24-004, "Notice of Special Interest (NOSI): U.S. Health in the International Perspective". See Notice NOT-AG-24-015
  • May 7, 2020 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed). See NOFO PA-20-200.
  • May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183.
  • May 5, 2020 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See NOFO PA-20-184.
  • May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Institute on Aging (NIA)


This NOSI expresses NIA’s interest in research that examines mechanisms and causes behind the increasing U.S. health disadvantage, which refers to worsening life expectancies and health outcomes in the U.S. compared to other countries. Of particular interest are projects that examine cross-national and U.S. cross-regional or cross-state differences in policy context that may drive poor health outcomes. 


Despite large increases in life expectancy throughout the twentieth century, U.S. life expectancy has fallen behind other comparable countries in the twenty-first century. During the past decade, U.S. life expectancy has even decreased compared to earlier generations. While U.S. populations have been differentially affected, this trend is affecting nearly all U.S. citizens and residents regardless of age, race/ethnicity, geographies, and regions. 

A 2013 National Academies of Science, Engineering and Medicine (NASEM) report, U.S. Health in the International Perspective: Shorter Lives, Poorer Health explored whether this observed lowered life expectancy among Americans was due to deaths earlier in the life course. The report found that the trend was driven, in part, by stark increases in middle-age and younger adult (25-64 years) mortality. A 2021 report led by the NASEM, High and Rising Mortality Rates Among Working-Age Adults, further investigated this finding. It identified three proximate causes of death that are higher in the U.S. compared to other countries including: substance use, increasing rates of suicide, and poorer cardiovascular health among Americans compared to their peers in other countries. Substance use as a cause of death encompasses drug poisoning, alcohol-related causes, and the sharp increase in opioid use that did not occur to nearly the same extent in other countries. Cardiovascular health declines occur along several dimensions including both increases in and slowing of improvements of endocrine, nutritional, and metabolic diseases; hypertensive heart disease; and ischemic heart disease and other diseases of the circulatory system. The relative U.S. disadvantage may be due to the obesity epidemic; social, economic, and cultural changes; or less dramatic decreases in cardiometabolic risk from medical intervention. While liver cancer, nervous system diseases, homicide, and transport injury are identified as other potential drivers of falling US life expectancy, substance use, cardiovascular health declines, and obesity constituted the top three drivers of deaths among middle-aged and older adults in recent decades. These causes of death are not comprehensive; for example, the analysis presented in these reports took place prior to the COVID-19 pandemic. The complex, multifactorial pathways across the life course leading to these proximate causes of death warrant further investigation.

To build off the work described above, this NOSI seeks research that investigates the upstream factors leading to the top causes of death, disease, and disability uncovered by the 2021 NASEM report, including multimorbidity. In particular, this NOSI encourages research that leverages differences between macro- and meso-level social and environmental factors at the country, region, and/or state-level to elucidate. Examples of macro-level social factors include social safety net policy, economic conditions, and employment. Meso-level social factor examples include the role of institutions, neighborhood, community organizations, and social networks. These comparisons could be between the U.S. and other comparable high-income countries or low- and middle-income countries (LMICs). The comparisons could also be between U.S. regions, states, or other geographies. Macrosocial environments are not static; thus, examining health outcomes related to variations in macrosocial factors within a context may prove informative.

In addition to mortality, the outcomes this NOSI seeks proposals for are health (broadly defined) across the life course and aging. Applications proposing analysis of existing data collected in LMICs are welcomed, as LMICs often have greater variation and speed of change in their policy contexts compared to high-income countries. Similarly, U.S. states and regions have contextual differences that may produce (dis)advantage, and proposals leveraging such natural experiments to identify causal drivers are welcome.

Relevant data resources could include the U.S. Health and Retirement Study (HRS) (can be accessed through the Gateway to Global Aging), International Family of HRS studies, and the Harmonized Cognitive Assessment Protocol (HCAP). There are likely other data resources that are appropriate for projects proposed as part of this NOSI.

Areas of interest include but are not limited to:

  • Research comparing cross-national health disadvantage by leveraging cohort comparisons with cross-sectional and longitudinal data that considers multiple contextual factors and their interactions to identify causes over the life course.
  • Research exploring differences in protective factors between the U.S. and other countries that may ameliorate the effects of certain social determinants of health, such as poverty, particularly among older adults.
  • Research that identifies and explores drivers of life expectancy increases in high-income countries other than the U.S., and how various national indicators of income, education, health, and health care, and within country inequalities in these indicators, labor market conditions, social welfare, and other regulations are linked to differences in life expectancies.
  • Research examining the effects of policy shifts within major institutions or systems that foster society-level change, such as educational, economic, political, environmental, and health systems. The effects on individuals throughout their life span and communities should be considered.
  • Research on social protection policies, such as pensions, cash transfers, and other economic support provisions that examine not only individual receipt but also impact of such policies on social determinants of health and outcomes at the population level with attention to subgroups, and causal inference. Designs could include research that uses randomized controlled trial and/or natural experiment designs to examine the effects of social protection policies.
  • Research that focuses on whether and to what extent Americans with a high health and social status—as defined by race and ethnicity (e.g., non-Hispanic Whites), education, income, insurance status, and risk factors (e.g., nonsmokers, nonobese)—are in worse health than populations and subpopulations in comparable countries at various points in their lives, identifying any specific health conditions (and including multimorbidity) where outcomes may differ, and examining drivers.
  • Research that examines how the causes of changes in life expectancy over the last century in the U.S. vary by subgroups, such as race/ethnicity, sex and gender, socioeconomic position, and age distributions. 
  • Studies that use multilevel designs, such as combining individual and country-level data, to examine the causes of increasing suicide rates over the life course among groups most affected.
  • Research that examines contextual factors that may drive higher and increasing suicide rates—and its causes, such as increasing substance use, declining mental health, or multimorbidity—among communities adversely affected by suicide, particularly studies that compare drivers by racial and ethnic subgroups. These studies could further explore how economic and social factors associated with suicide differ between subgroups (e.g., sex and gender, sexual orientation and gender identity, age, race and ethnicity, geography, etc.).
  • Research that explores contextual factors over the life course (e.g., early life trauma or adversities, access to and availability of lethal means) that may affect means of suicide and variation by subgroups (e.g., age, sex).

Application and Submission Information

This notice applies to due dates on or after June 5, 2024 and subsequent receipt dates through May 8, 2027. 

Submit applications for this initiative using one of the following notices of funding opportunities (NOFOs) or any reissues of these announcements through the expiration date of this notice.

All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-AG-24-004” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Kriti M. Jain, Ph.D.
National Institute on Aging (NIA) 
Telephone: 202-740-6701