1. Tony Punturieri, M.D., Ph.D. Telephone: 301-435-0230 Email: punturieria@nhlbi.nih.govpunturieria@nhlbi.nih.gov FOA RFA-HL-16-012: Health Outcomes Trial (UM1) Household Air Pollution (HAP) Trial

2. Household Air Pollution in Low- and Middle-Income Countries: Health Risks and Research Priorities William J. Martin, II 1 *, Roger I. Glass 2, Houmam Araj 3, John Balbus 4, Francis S. Collins 5, Siaˆ n Curtis 6, Gregory B. Diette 7, William N. Elwood 8, Henry Falk 9, Patricia L. Hibberd 10, Susan E. J. Keown 11, Sumi Mehta 12, Erin Patrick 13, Julia Rosenbaum 14, Amir Sapkota 15, H. Eser Tolunay 16, Nigel G. Bruce 17 1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America, 2 John E. Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America, 3 National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 4 National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America, 5 National Institutes of Health, Bethesda, Maryland, United States of America, 6 MEASURE Evaluation Project at the Carolina Population Center and the Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 7 School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 8 Office of Behavioral and Social Sciences Research, National Institutes of Health, Bethesda, Maryland, United States of America, 9 Office of Noncommunicable Diseases, Injury and Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 10 Division of Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 11 Palladian Partners, Silver Spring, Maryland, United States of America, 12 Global Alliance for Clean Cookstoves, Washington, District of Columbia, United States of America, 13 Women’s Refugee Commission, New York, New York, United States of America, 14 FHI 360, Washington, District of Columbia, United States of America, 15 School of Public Health, University of Maryland, College Park, Maryland, United States of America, 16 Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 17 Department of Public Health and Policy at the University of Liverpool, Liverpool, United Kingdom and the Department of Public Health and Environment at the World Health Organization, Geneva, Switzerland Policy Forum 2011 NIH Conference on Household Air Pollution and Cookstoves

3.  Will conduct a clinical trial across three or more Low and Middle Income Country (LMIC) settings  Will test improved stove and fuel interventions on health outcomes in exposed populations.  Will be a cooperative agreement research grant (UM1) Published HAP FOA

4. MAIN COMPONENT WILL HAVE MULTIPLE FUNCTIONS Coordinating Center:  Manage and conduct operations related to the ideation and implementation of a clinical trial.  Follow-up and report to NHLBI recruitment and implementation of the trial at the sites.  Organize Steering Committee, Investigators in person meetings, phone calls, provide payments related to protocol implementation.  Organize the DSMB in person meetings, report to DSMB and NHLBI AEs.  Provide reports of activities to the B&MGF HAP FOA: component 1

5. MAIN COMPONENT WILL HAVE MULTIPLE FUNCTIONS Propose and Supervise the implementation of the trial. The trial will:  Test the impact of improved stove and fuel interventions and, when applicable, second-hand cigarette smoke reduction on health outcomes in exposed populations.  Assess short-term (4-5 years) health outcomes: with a particular focus on women and children. Indicators of potential long-term health outcomes in this population should also be assessed.  Low birth weight and higher infant mortality, increased respiratory infections, wheezing in children, and increased rates of stroke, cardiovascular disease, lung cancer, eye disorders, burn and other injuries in adults.  Develop and implement an environmental monitoring strategy for the selected stove/fuel used in the intervention trial. HAP FOA: component 1

6. Second component (with specific budget, may not be funded):  Will include a biomarker center for the development and validation of clinical, physiological, chemical and biochemical markers of exposure and pathophysiological responses.  The biomarker development and validation will be led by a PD/PI other than the one of the clinical study.  The PD(s)/PI(s) of both projects will collaborate closely to create a seamless research process and integrated data set that analyzes and connects the outcomes of the clinical trial with the biomarker data.  In some circumstances the PD/PI of the biomarker project may need to perform biomarker analyses within the LMIC where the samples have been collected. HAP FOA: component 2

7. A Public/Private partnership: NIEHS, NICHD, NCI, FIC, NHLBI NIH-CF BMGF (GACC) Budget 31+ (5) mill. Award FY 2016 Application Due Date: January 19, 2016, by 5:00 PM local time of applicant organization. HAP FOA

8. Total funds available for the five year grant: $5,000,000 TC /year for trial and overall management $1,200,000 TC /year for biomarker center Direct Costs $5,075,000/year, subdivided as such:  Core and recruitment system funds (to a US Institution) may be requested at up to $1,297,000 direct costs per year.  Protocol (capitation) funds may be requested at up to $3,000,000 per year.  (These will be to a foreign Institution in a LMIC given by the US Core Management Institution and are inclusive of 8 percent F&A costs for foreign grantees as stated in the information on allowable and unallowable costs for foreign grantees, in the NIH Grants Policy Statement Section 16.6).NIH Grants Policy Statement  The biomarker development and validation study (led by a US Institution) may not exceed $778,000 direct costs per year. Budget HAP FOA