Cancer, NCDs & Global Health: Perspectives from the US NCI

1. Cancer, NCDs & Global Health:Perspectives from the US NCI Edward L Trimble, MD, MPH Rutgers International Research Conference July 2016

2. Outline of talk • Global burden of cancer & NCDs • Global response to global burden of NCDs • USA government support for global health and biomedical research • US NCI global health research

3. NCDs and Injury in LMICs More than 70% of premature deaths in LMICs are caused by NCDs and injury Data Source: WHO Data Health Statistics And information system, 2012

4. DALYs for Communicable Diseases vs. NCDs Cardiovascular Disease 11.8% Communicable Diseases (46%) Injuries 11.2% Non-Communicable Diseases (54%) 46% Cancer 7.6% 7.4% Mental Health and Behavioral Disorders 6.8% 4.7% 4.5% Musculoskeletal Disorders Chronic Respiratory Other NCDs Data Source: Institute for Health Metrics and Evaluation, Global Burden of Disease Study, 2013

5. NCDs Have Common Risk Factors • Tobacco use • Physical inactivity • Unhealthy diet • Harmful use of alcohol • Environmental factors • Outdoor air pollution • Indoor air pollution

6. % Increase 2012-2030 • Where will the burden fall – development? 0 10 20 30 40 50 60 70 80 90 100% million new cases Assuming no change in underlying incidence Bray F et al. Global cancer transitions according to the Human Development Index (2008-2030): a population based study. Lancet Oncol 2012; 13:790-801

7. Global health priorities • United Nations 2011 High-Level Meeting on NCDs • WHO 2013 Action Plan for Prevention and Control of NCDs • World Bank Disease Control Priorities • http://www.dcp-3.org/ • Global Burden of Disease, Institute for Health Metrics and Evaluation, University of Washington • United Nations Sustainable Development Goals, 2015

8. WHO global NCD targets

9. WHO Global NCD Monitoring Framework

10. Global NCD Monitoring • Mortality and Morbidity • Cancer registries; death registries • Risk Factors • Alcohol; tobacco; overweight & obesity; inactivity • National Systems Response • HBV & HPV vaccines; access to essential meds & technologies; palliative care

11. SDG Goal 3: Targets • By 2030, reduce the global maternal mortality ratio to less than 70 per 100,000 live births • By 2030, end preventable deaths of newborns and children under 5 years of age, with all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births

12. SDG Goal 3: Targets • By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases • By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being

13. SDG Goal 3: Targets • Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol [decrease risk of hepatitis transmission & cancers linked to alcohol) • By 2020, halve the number of global deaths and injuries from road traffic accidents 3.7 By 2030, ensure universal access to sexual and reproductive health-care services, including for family planning, information and education, and the integration of reproductive health into national strategies and programmes[need to improve access to surgery, anesthesia, & clinical laboratory services; can build HPV screening and breast health into reproductive health services]

14. SDG Goal 3: Targets • Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all • By 2030, substantially reduce the number of deaths and illnesses from hazardous chemicals and air, water and soil pollution and contamination

15. SDG Goal 3: Targets • Strengthen the implementation of the World Health Organization Framework Convention on Tobacco Control in all countries, as appropriate

16. SDG Goal 3: Targets • Support the research and development of vaccines and medicines for the communicable and noncommunicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS Agreement and Public Health, which affirms the right of developing countries to use to the full the provisions in the Agreement on Trade Related Aspects of Intellectual Property Rights regarding flexibilities to protect public health, and, in particular, provide access to medicines for all

17. SDG Goal 3: Targets • Substantially increase health financing and the recruitment, development, training and retention of the health workforce in developing countries, especially in least developed countries and small island developing States • Strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks

18. Development assistance for NCDs • US Council on Foreign Relations: • Task Force Report: The Emerging Global Health Crisis: NCDs in Low- and Middle-Income Countries, 2014 • 2010 international aid $ per DALY: $69/HIV-AIDS, $16/malaria, $5/MCH, $0.09/NCDs

19. US government support for global health programs • Department of State • USAID: maternal-child health, infectious diseases • President’s Emergency Fund for AIDS Relief (PEPFAR) • Global Fund to Fight AIDS, TB & Malaria • Department of Defense • Department of Health and Human Services • Centers for Disease Control & Prevention

20. US government support of biomedical research • Department of Health and Human Services • Centers for Disease Control & Prevention • National Institutes of Health • Department of Defence • Primarily tropical diseases and injury; some smaller Congressionally-mandated research programs • NASA • Space medicine

21. US National Institutes of Health • Annual budget $30 billion (US) • 27 institutes and centers • $1.2 billion focused on global health research • National Cancer Institute • $5 billion annual budget • 15% intramural (epidemiology, basic/translational/clinical research) • 85% extramural research

22. US NCI and CDC collaborations • Cancer registration • Cancer education and communications • Cancer control planning • Tobacco control research • Also with US FDA • Cancer Screening • Also with US FDA • Quality of cancer care • Also with CMS and FDA

23. NCI Priorities in Global Health • Strengthening global cancer research • Building a global cancer research community • Translating research results into practice

24. NCI Priorities in Global Health • Strengthening global cancer research • Affordable Cancer Technology • Building a global cancer research community • Cancer & NCD Research Centers of Excellence • Translating research results into practice • Metrics: improving diagnosis; surveillance • Tobacco control; HPV vaccines and screening

25. Technology Development Pipeline Global Health Deployment Discovery Prototype Multi-Site Validation in GH Commercialization Academia/Small business Ministries of Health NGOs Pharma & device industry IMAT SBIR BRG BRP

26. Need for multidisciplinary teams Oncology Engineering Global Health Business Universities Community Groups NGO Charities Industry Hospitals Local Low Resource Area

27. Affordable Cancer Technologies Result of collaboration by Program Directors across NCI Divisions, Offices, and Centers to identify priority areas and manage grants. Critical Elements • Two-phase cooperative agreement. • Three Rounds: Awards run until 2022. • Phase I (UH2) - two years: • Demonstrate initial clinical potential of device/assay for application in a global health setting. • Adaptations/engineering to device/assay for use in LMIC setting. • Phase II (UH3) - three years: • Validate device in global health setting • Progression from UH2 to UH3: • Grantee must meet specified milestones • Milestones reviewed by NCI program staff.

28. Affordable Cancer Technologies Program: Funded Projects (Round 1) High Resolution Micro-endoscopy (HRME) for RT Imaging of Cervical Neoplasia GeneXpert HPV DNA Assay Photodynamic Therapy for Oral Cancer Cryopop CryoPen Portable US Imaging of Palpable Breast Masses Point-of-care viral load test for HCV

29. Affordable Cancer Technologies Program: Funded Projects (Round 2) • The Radiation Planning Assistant for Radiation Planning in Low- and Middle-Income Countries • Smartphone for Molecular Cancer Diagnostic In Africa • Cytology-Free POC Cervical Cancer Diagnostics for Global Health • Low-cost Mobile Oral Cancer Screening for Low Resource Setting • Development, field testing and evaluation of the efficacy of a hand-held, portable and affordable thermo-coagulator to prevent cervical cancer in low- and middle- income countries • Development and clinical validation of a multi-type HPV E6/E7 oncoprotein test for cervical cancer screening and triage in low- and middle-income countries • Early Stage Diagnosis of Kaposi’s Sarcoma in Limited Resource Settings Using KS-Detect

30. NCI & CGH’s Priorities in Global Health • Cancer and NCDs Centers of Research Excellence • Strengthening global cancer research • Building a global cancer research community • Translating research results into practice

31. Ghana University of Michigan Intervention study with traditional healers Johns Hopkins University Cervical Cancer Prevention Program Thomas Jefferson University Prostate cancer study Stanford University Prostate cancer screening study Vanderbilt University Colorectal cancer study University of Chicago Breast cancer treatment study

32. UK Universities Working in Ghana • Barts Cancer Institute • Institute for Cancer Research, London • Kings College, London • Leeds • NICE • Queens University, Belfast • Royal Marsden Hospital • University College, London • University of Warwick • University of Bristol • University of Cambridge • University of London, Imperial College • University of Glasgow • University of Manchester • University of Reading • University of Oxford • University of Southampton • University of Surrey

33. AMPATH Model Founders: • Goal: To create a sustainable research program including Research Program Office; Research and Sponsored Programs; Institutional Review Board; and ISO certified laboratory • Overarching Principle: Each Research Project must have both a North American and a Kenyan principal investigator • Established: In 1998; based in El Doret, Kenya www.ampathkenya.org Indiana University, Moi University SOM MoiTeaching & Referral Hospital

34. AMPATH Model • Current Leadership: Dr. Rachel Vreeman, Indiana University and Dr. WinstoneNyandiko, MoiUniversity • Kenya Partners: Moi University School of Medicine and Moi Teaching and Referral Hospital • USG Partner: USAID-PEPFAR and five NCI-designated Cancer Centers • North American Partners: Indiana Univ., Brown Univ., Duke Univ., Lehigh Valley Hospital, Provident Portland Medical Center, Purdue Univ., Univ. of Massachusetts, Univ. of Toronto, and Univ. of Utah www.ampathkenya.org

35. AMPATH Program Structure • 5 Co-Field Directors for Research 3 are full-time in Kenya • 9 Research Working Groups Adult medicine, Basic science, Behavioral & social science, Cardiovascular and pulmonary disease, Oncology, Pediatrics, Public health & primary care, Reproductive health, and Tuberculosis • 7 Core Facilities Operations, Data management, Biostatistics, Clinical informatics, Pharmacy, Laboratory, and Bioethics

36. AMPATH Outcomes, 17 Years Later • Over 90 active research projects • More than $83.4M in research funding • Collaborators from > 19 universities and academic institutions in Africa, Europe, and North America • More than 275 publications

37. Regional Centers of Excellence NCD Research • Non-communicable diseases in low- and middle-income countries • Broad definition of NCDs, includes mental health, trauma, surgery, hematology, palliative care, etc • Planning grants (P20), $200,000 per year for 2 years • Consortia of HIC and LMIC institutions working in selected region or country

38. Regional Centers of NCD Research Excellence • NCI developed FOA with input from other NIH institutes; we will ask them to consider co-sponsoring • NCI plans follow-up FOA to build the Centers of Research Excellence • NCI will ask other countries to fund the participation of their universities in relevant consortia • Australia, China, Denmark, France, Germany, Ireland, Japan, Korea, NZ, Netherlands, Norway, Sweden, etc

39. RCRE in Cancer and Other NCDs Disease Epidemiology and Prevention in VietnamP20 CA210300 Priority Score: 14co-PI: Dr. Xiao-Ou Shu Vanderbilt Universityco-PI: Dr. Thuan Van Tran National Inst. for Cancer Control Vietnam Description of Project: To build a RCRE in Vietnam to establish a large population-based cohort study to examine the influence of westernization on NCDs in Vietnam Anticipated Outcomes from the Pilot Studies: • Case-control study for breast cancer • Cross-sectional community-based survey of type 2 diabetes Shared Resources: • Survey Research Support Core • Biospecimen Processing and Biorepository Core • Bioinformatics and Informatics Core

40. RCRE in South Africa and BotswanaP20 CA210283 Priority Score: 17co-PI: Dr. Neo Tapela Botswana Harvard AIDS Instituteco-PI: Dr. Bruce Chabner Massachusetts General Hospitalco-PI: Dr. ShahinLockman Harvard Medical Schoolco-PI: Dr. Doreen Ramogola-Masire Botswana UPenn Partnership Description of Project: To strengthen data for breast cancer, hypertension, and road-traffic accident trauma research in Botswana and South Africa Anticipated Outcomes from the Pilot Studies: • To develop eHIS in South Africa to generate quality data elements for breast cancer studies • To expand the Integrated Patient Management System in Botswana to include HTN and trauma Shared Resources: • Data acquisition • Data aggregation and management • Biostatistics

41. RCRE in MalawiP20 CA210285 Priority Score: 17co-PI: Dr. Satish Gopal University of North Carolina Chapel Hillco-PI: Dr. Dirk Dittmer University of North Carolina Chapel Hillco-PI: Dr. MwapatsaMipando University of Malawi College of Medicineco-PI: Dr. NyengoMkandawire University of Malawi College of Medicine Description of Project: To build a RCRE in Malawi that will serve as regional research resource for cancer pathology and trauma surgery training Anticipated Outcomes from the Pilot Studies: To identify a molecular signature carcinogen-associated esophageal squamous cell carcinoma Shared Resources: • Clinical • Laboratory • Epidemiology

42. Mesoamerican Center for Population Health Research on NCDsMexico, Guatemala, Costa Rico, and ColombiaP20 CA210286 Priority Score: 19co-PI: Dr. Martin Lajous Instituto Nacional de SaludPublicaco-PI: Dr. Ruy Lopez-RidauraInstituto Nacional de SaludPublica Description of Project: To pool existing expertise, resources and infrastructure to build sustainable cancer and diabetes research programs Anticipated Outcomes from the Pilot Studies: To analyze prospective observational data from the MTC to provide evidence about the social and biological risk factors for NCDs Shared Resources: • Study Design, Analysis, and Dissemination Unit • Human Subjects’ Research Unit • Funding Opportunity Monitoring and Grants Management Unit

43. Bangladesh Center for Research Excellence in NCDsP20 CA210305 Priority Score: 20co-PI: Dr. Habibul Ahsan University of Chicagoco-PI: Dr. Syed Shariful Islam Bangabandu Sheikh Mujib Medical University Description of Project: To investigate the determinants of women’s cancers and CVD to lead to better informed policies and care in Bangladesh Anticipated Outcomes from the Pilot Studies: To create a pathology-based cancer registry to study the distribution of breast, uterine, & cervical cancers To evaluate how the gut microbiome contributes to subclinical markers of CVD Shared Resources: • Data Management, Statistics and Informatics Core • Biomarker Core • Population Survey and Data Collection Core • Clinical and Diagnostics Core

44. Global tobacco control • Framework Convention for Tobacco Control; adopted 2003; active 2005 • First global treaty focused on health • Signed by 168 countries; legally binding in 178 countries

45. Tobacco control research • NIH International Tobacco and Health Research and Capacity Building Program • NIH Tobacco Regulatory Science Program • Tobacco or Health global and regional conferences • Society for Research on Nicotine and Tobacco

46. NCI & CGH’s Priorities in Global Health • National case study: Kenya • Strengthening global cancer research • Building a global cancer research community • Translating research results into practice

47. Case Study: Kenya • Request from Government of Kenya for help with cancer control and cancer research • Major USG investment with CDC and USAID • Cancer Centers and US universities working in Kenya; numerous other NIH ICs • Political will in Kenya to prioritize cancer control • Regional cancer research opportunities

48. Research Opportunities in Kenya • Esophageal cancer • Burkitt Lymphoma • Diagnosis of breast cancer via FNA • Women’s cancers and stigma • Delay from diagnosis to treatment • Implementation science for HPV vaccine roll-out and cervical cancer screening/ follow-up

49. Joining Forces to Overcome Cancer: The Kenya Cancer Research and Control Stakeholder Program CGH portfolio analysis identifies significant investment in Kenya, but lack of coordination among stakeholders and the national government. 8 NCI-designated Cancer Centers investing in cancer research. NCI-Kenya establishes technical working groups as a direct result of the meeting tracks; Government of Kenya matches NCI-US investment in cancer registries and surveillance. CGH convenes National Stakeholder Meeting with more than 40 organizations and 80 individuals, across 4 key technical areas. CGH conducts evaluation showing that efforts have resulted in research capacity building, increased grant submissions, and increased collaboration. 2016 - 2017 2015 2014 2013

50. Direct Impact/Outcomes by NCI/CGH Priority Areas