The NCI Office of Cancer Centers Learning Series Complementary and Alternative Medicine Cancer Research and the National

1. The NCI Office of Cancer Centers Learning SeriesComplementary and Alternative Medicine Cancer Research and the National Cancer Institute Dial In: 888-324-6921 Passcode: Cancer CentersFor Technical Support, call 800-857-8777 and choose option 3.

2. The NCI Office of Cancer Centers Learning Series Complementary and Alternative Medicine Cancer Research and the National Cancer Institute Tuesday, September 11, 2012 2:00 to 3:00 pm EDT Moderator Shannon Silkensen, Ph.D. Program Director Office of Cancer Centers National Cancer Institute National Institutes of Health Bethesda, MD Featured Presenters Jeffrey D. White, M.D.Director, Office of Cancer Complementary and Alternative Medicine (OCCAM) Division of Cancer Treatment and Diagnosis, NCI Dan Xi, Ph.D. Program Director, Office of Cancer Complementary and Alternative Medicine (OCCAM) Division of Cancer Treatment and Diagnosis, NCI Lorenzo Cohen, Ph.D. Professor and Director of the Integrative Medicine Program MD Anderson Cancer Center, Houston, TX

3. A Quick Guide to Your Screen • Please submit your question via the Q & A box on the right hand side of your screen. If you do not see the Q&A box, you can expand it by clicking the Q&A on the top navigation panel and dragging the box that opens to the right side of your screen.

4. NCI’s Complementary and Alternative Medicine Activities: A Brief Overview Cancer Centers WebinarSeptember 11, 2012Jeffrey D. White, M.D.Director, Office of Cancer Complementary and Alternative Medicine, NCI

5. Terminology and Definitions Complementary and Alternative Medicine (CAM) • “Medical and health care practices that are not an integral part of conventional (Western) medicine.” (National Center for Complementary and Alternative Medicine) • “…a broad set of health care practices that are not part of that country’s own tradition and are not integrated in the dominant health care system.” (World Health Organization)

6. Terminology and Definitions Complementary and Alternative Medicine (CAM) • Complementary – Used in combination with conventional treatment • Alternative – Used instead of conventional treatment Integrative Medicine • Combination of conventional (Western) medicine and components of other medical traditions or other unconventional modalities with sufficient evidence-based support.

7. Major Domains of Complementary and Alternative Medicine Research (NCI, OCCAM) • Alternative Medical Systems and some of their components (e.g. Traditional Chinese Medicine, Homeopathy, acupuncture) • Energy Therapy • Electromagnetic (e.g. electrochemotherapy) • Theoretical (e.g. Reiki, Qi gong) • Exercise • Western forms (e.g. aerobic, isometric) • Other (e.g. T’ai Chi, yoga) • Manipulative and Body-Based Therapies (Therapeutic massage, Osteopathy, Chiropractice)

8. Major Domains of Complementary and Alternative Medicine Research (NCI, OCCAM) • Mind-Body Interventions (e.g. hypnosis, imagery, relaxation therapy) • Nutritional Therapeutics (e.g. diet modification, specific foods, nutrients, bioactive food components) • Pharmacological and Biologically-based Therapies • Complex natural products (e.g. botanicals, extracts from marine animals [e.g. shark cartilage]) • Off-label use of certain drugs not traditionally used as cancer therapies (e.g. naltrexone) • Spirituality and Spiritual Healing • Miscellaneous • Chronobiology and Chronotherapy

9. Comparative analysis of CAM use by the U.S. Cancer and Non-Cancer populations* • Secondary analysis of the 2002 NHIS Survey • 31,044 respondents • 28,734 individuals without prior CA diagnosis • 2,262 cancer survivors • 461 diagnosed within the last 12 months • 1786 diagnosed > 12 months prior • Results: • Cancer survivors use CAM more frequently than individuals without a cancer diagnosis (39.2% vs. 34.9%, p<0.001 *Fouladbakhsh JM, Strommel M. Journal of Complementary and Integrative Medicine 2008;5(1): Art. 19 (Epub)

10. NCI’s Annual Report on Complementary and Alternative Medicine 2010 PDF version is available on the OCCAM website (http://cancer.gov/cam)

11. NCI’s CAM Expenditures Fiscal Years 2003-2010 From: NCI’s Annual Report on Complementary and Alternative Medicine: Fiscal Year 2010, NIH Publication No. 11-7768, Feb. 2012

12. NCI’s Cancer CAM Portfolio FY2010 • Overview • > 400 projects, approx. $114.4 million • Extramural - Grants, cooperative agreements and contracts • Diffusely represented throughout portfolios of the four grant making extramural divisions (DCB, DCCPS, DCP, DCTD) – Over 50 different PDs • Intramural (CCR and DCEG) – Projects and contracts CCR = Center for Cancer Research; DCB = Div. of Cancer Biology; DCEG = Div. of Cancer Epidemiology and Genetics; DCP = Div. of Cancer Prevention; DCCPS = Div. of Cancer Control and Pop. Sciences; DCTD = Div. of Cancer Treatment and Diagnosis

13. NCI CAM Research Projects by CAM Category From: NCI’s Annual Report on Complementary and Alternative Medicine: Fiscal Year 2010, NIH Publication No. 11-7768, Feb. 2012

14. Office of Cancer Complementary and Alternative Medicine, NCI OCCAM established in October 1998 • Director: Jeffrey D. White, M.D. • Organizational Location: Division of Cancer Treatment and Diagnosis (Formerly in the Office of the Director) • Physical Location: 6116 Executive Blvd., Suite 609, Bethesda, MD 20892 • Program Areas: • Grant Portfolio • Communications and Outreach • Practice Assessment

15. Mission of OCCAM • To improve the quality of care of cancer patients, as well as those at risk for cancer and those recovering from cancer treatment, by contributing to the advancement of evidence-based CAM practice, the sciences that support it and to the availability of high-quality information for the healthcare community, researchers and the general public.

16. OCCAM’s International Research Collaborations

17. OCCAM supported NCI – Beijing Guang’anmen Hospital Traditional Chinese Medicine Study Project The collaborative study of TCM Shen Qi Formula (SQF) - an extract from two herbs: Astragalus mongholicus Bge, and Panax notoginseng) - has found: • SQF has direct inhibitory effect on the proliferation of mouse 4T1 mammary tumor cells. • The inhibitory effect of whole SQF extracts on mouse 4T1 tumor cell is greater than its individual major ingredients or the combination of major ingredients. • SQF treatment up-regulated pro-apoptosis genes (Bad and Apaf1), and down-regulated anti-apoptosis gene Bcl2.

18. OCCAM supported NCI – Kunming Institute of Botany (KIB) Anti-cancer Agents Screening Project • Established collaboration in October 2008, an MOU was signed between NCI and KIB. • Compounds from KIB were sent to NCI to start the anti-cancer activity screening on NCI 60 human cancer cell lines in 2009. • Total of 58 compounds have been screened on NCI 60. • 36 single concentration screening • 11 compounds had 5 conc. Screening • None to animal testing • Molecular Targets Development Program has also investigated these compounds assays examining effects on specific cellular signaling pathways, such as TRAIL, AP-1, HIF-2

19. OCCAM supported NCI – Key Laboratory of Chemistry for Natural Products of GuizhouAnti-cancer Agents Screening Project • Established collaboration on anti-cancer agents screening in December 2009. • An MOU was singed between NCI and Key Lab of Chemistry for Natural Products (KLCNP) of Guizhou in March 2010. • More than 200 compounds from KLCNP of Guizhou were sent to NCI to start the anti-cancer activity screening on NCI 60 human cancer cell lines in 2010. • 38 so far in one conc. testing and 3 on to 5 conc. • KLCNP of Guizhou also sent 150 regional-specific herbal extracts to NCI in 2011 for potential anti-cancer activity screening.

20. Communications and Outreach Program

21. Communications and Outreach Program Promotes NCI CAM research activities, events, and initiatives • Develops print and online information products on cancer CAM for healthcare professionals and the general public, including the website: http://www.cancer.gov/cam. • NCI Annual Report on Complementary and Alternative Medicine • CAM PDQ support • Research/practitioner listserv for NCI CAM related events and news • Invited lecturers • NCI CAM News, our twice-yearly newsletter • Patient Education resources

23. The NCI Office of Cancer Centers Learning Series Complementary and Alternative Medicine Cancer Research and the National Cancer Institute Questions? Please submit your question via the Q & A box on the right hand side of your screen. If you do not see the Q&A box, you can expand it by clicking the Q&A on the top navigation panel and dragging the box that appears it to the right side of your screen. Jeffrey D. White, M.D.Director, Office of Cancer Complementary and Alternative Medicine (OCCAM) Division of Cancer Treatment and Diagnosis, NCI

24. NCI Cancer CAM Funding Opportunities and Grant writing Dan Xi, Ph.D. Program Director (xida@mail.nih.gov) Office of Cancer Complementary and Alternative Medicine (OCCAM) National Cancer Institute (NCI) National Institutes of Health (NIH) (http://www.cancer.gov/cam/index.html)

25. Objectives To share information about the OCCAM/NCI cancer CAM portfolio, funding opportunities and initiatives in cancer CAM research, as well as some aspects on strategies for grant writing

26. Research Grant Funding and Portfolio at OCCAM, NCI • Major Functions: • Analyze NCI cancer CAM portfolio • Identify gaps in existing cancer CAM research • Develop evidence-based scientific foundation of the field • Create and expand funding opportunities to stimulate high quality research in cancer CAM • Provide technical assistance to applicants • Manage grants of cancer CAM interventions for treatment • Coordinate the cancer CAM grant activities at NCI • Program Philosophy: Keep CAM research integrated within the relevant NCI scientific programs (e.g. prevention, symptom management and supportive care, survivorship and behavioral medicine etc.)

27. OCCAM’s Research Priorities • Identifying novel therapeutics in the pharmacopeia of traditional medical systems as defined by the World Health Organization • Using complementary approaches to improve the therapeutic ratio of standard and investigational anti-cancer therapies • Research on lifestyle modifications (e.g. diet, exercise, mind-body approaches) for their impact on cancer outcomes (e.g. response to conventional cancer therapy, survival)

28. Types of NIH Grant Funding Programs(http://grants.nih.gov/grants/funding/funding_program.htm) The following represents some main types of grant funding programs in the cancer CAM research: R01: NIH Research Project Grant Program (R01) • Used to support a discrete, specified, circumscribed research project • NIH's most commonly used grant program • No specific dollar limit unless specified in FOA • Advance permission required for $500K or more (direct costs) in any year • Generally awarded for 3 -5 years • NCI use NIH parent FOA: PA-11-260 (http://grants.nih.gov/grants/guide/pa-files/PA-11-260.html) OCCAM Active Grant Portfolio 2011-2012 (R01)

29. Types of NIH Grant Funding Programs R21: NIH Exploratory/Developmental Research Grant Award (R21) • Encourages new, exploratory and developmental research projects by providing support for the early stages of project development. Sometimes used for pilot and feasibility studies. • Limited to up to two years of funding • Combined budget for direct costs for the two year project period usually may not exceed $275,000. • No preliminary data is generally required • See NCI specific PAR-12-145 R03 NIH Small Grant Program (R03): • Provides limited funding for a short period of time to support a variety of types of projects, including: pilot or feasibility studies, collection of preliminary data, secondary analysis of existing data, small, self-contained research projects, development of new research technology, etc. • Limited to two years of funding • Direct costs generally up to $50,000 per year • Not renewable • See NCI specific PAR-12-144

30. OCCAM Active Grant Portfolio 2011-2012 (R21)

31. Other OCCAM Active Grant Portfolio 2011-2012 (P01 and R13) P01: Research Program Project Grant • Support for integrated, multi-project research projects involving a number of independent investigators who share knowledge and common resources • Each project contributes or is directly related to the common theme of the total research effort, thus forming a system of research activities and projects directed toward a well-defined research program goal • See NCI specific FOA: PAR-12-005 (http://grants.nih.gov/grants/guide/pa-files/PAR-12-005.html) R13: NIH Support for Conferences and Scientific Meetings (R13 and U13) • Support for high quality conferences/scientific meetings that are relevant to NIH's scientific mission and to the public health • Requires advance permission from the funding IC • Foreign institutions are not eligible to apply • See NIH parent FOA: PA-12-212

32. Other OCCAM Active Grant Portfolio 2011-2012 (U01 and U19) Cooperative Agreement (U Series) A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

33. Grants Process At-a-Glance(http://grants.nih.gov/grants/grants_process.htm) Any successful project requires planning, development, implementation, and follow-through. Obtaining NIH funding for your research idea is no exception.  The Grants Process At-A-Glance Chart below provides an overview of the steps required for an application to proceed from application planning and submission through award and close out.  Look to the related resources for special guidance from NIH experts that can help maximize your understanding of the grants process and help you submit a successful grant application.

34. Grants Process At-a-Glance (continued)

35. Funding Opportunity Announcements Related to Cancer CAM(http://www.cancer.gov/cam/research_funding_apa.html) • NCI-wide Funding Opportunities *new* (R21 and R03) • OCCAM Participating Announcements • Behavioral/ Mind-Body • Diet, Nutrition & Physical Activity • Symptom Management • Survivorship *new* • Miscellaneous

36. Funding Opportunity Announcements Related to Cancer CAM Specific Research Objectives:All areas of cancer research relevant to the mission of the NCI are appropriate for projects submitted in response to this FOA [for a list of extramural research funding programs at the NCI, go to http://www.cancer.gov/researchandfunding/extramural]. Projects proposed in response to this FOA may involve basic, translational, clinical, and/or population research. Examples of relevant areas include but are not limited to studies of: cancer biology; cancer control; cancer diagnosis; cancer disparities; cancer prevention; and cancer treatment.

37. Funding Opportunity Announcements Related to Cancer CAM

38. Funding Opportunity Announcements Related to Cancer CAM

39. Funding Opportunity Announcements Related to Cancer CAM

40. Grant Application Information(http://www.cancer.gov/cam/research_applying.html) • Research Priorities: -OCCAM Research Priorities; -NCI Research Priorities • Tips for Writing a Grant: • Strategies for Success: How to Write a Cancer CAM Grant (PDF): Reviews issues unique to CAM related research areas and provides tips to writing a cancer CAM grant • Expert Opinions on Methodology: Development of Cancer CAM Symptom Research (PDF): Identifies CAM research methodology challenges and proposes potential solutions to assist grant applicants with future cancer CAM research proposals • Grant Application and Review Process: web links to NCI and NIH • Information for Grantees • Research Policies • Frequently Asked Questions about Research(http://www.cancer.gov/cam/research_faqs.html)

41. Frequently Asked Questions about Grant Applications(http://www.cancer.gov/cam/research_faqs.html) Where can I find information and guidance on preparing a grant application? Preparing to submit a grant application can feel overwhelming. Here are some suggestions to avoid some of the common pitfalls of grant applications: • Have a clear project description without complexity • Set realistic and not overly ambitious specific aims • Create a clear conceptual model • Strive for a well-defined methodology • Note the validity and replicability of the project • Cite background studies and references • Discuss statistical expertise and provide a clear data analysis plan • Have a plan for quality assurance • Note the expertise of investigator teams Additionally, please visit these NIH and NCI websites for more broad information about grant writing and submission. • NIH Office of Extramural Research Grant Writing Tips Sheets: http://grants1.nih.gov/grants/grant_tips.htm • NCI Grant Application and Review Process http://www.cancer.gov/researchandfunding/grantprocess

42. Frequently Asked Questions about Grant Applications(http://www.cancer.gov/cam/research_faqs.html) What review group would best fit the proposed application?Applicants can search for matching review groups at the following link: http://cms.csr.nih.gov/ Can an applicant propose a study review group or IRG for their application?Below are some recommendations on how to write a cover letter to propose a specific study section for your application. • Read about CSR Study Sections at: http://www.csr.nih.gov/Roster_proto/sectionI.asp • Identify an appropriate study section. • You can propose in your cover letter where your application appears to have the best fit. • You may suggest the inclusion of reviewers with specific scientific expertise. • You can indicate the name of the Program Director who has provided you with technical assistance with the Branch/Office. Does NCI or OCCAM have a CAM-specific review Special Emphasis Group (SEP)?No. Applications are evaluated for scientific and technical merit by (an) appropriate scientific review group(s) in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/) and under the section of “Application Review Information” in the Funding Opportunity Announcement (FOA). Most of applications of CAM cancer research have been reviewed by Center for Scientific Review (CSR)

43. Thank You

45. The NCI Office of Cancer Centers Learning Series Complementary and Alternative Medicine Cancer Research and the National Cancer Institute Questions? Please submit your question via the Q & A box on the right hand side of your screen. If you do not see the Q&A box, you can expand it by clicking the Q&A on the top navigation panel and dragging the box that appears it to the right side of your screen. Dan Xi, Ph.D. Program Director, Office of Cancer Complementary and Alternative Medicine (OCCAM) Division of Cancer Treatment and Diagnosis, NCI

46. Traditional Chinese Medicine and Other Research Opportunities in Integrative Oncology Lorenzo Cohen, PhD Director, Integrative Medicine Program

47. International Center of Traditional Chinese Medicine for Cancer Lorenzo Cohen, Ph.D., Principal Investigator/Co-Director Luming Liu, M.D., Co- Principal Investigator/Co-Director ZhiqiangMeng, M.D., Ph.D., Deputy Director • R21 (CA108084, NCI) • U19 (CA121530, NCI)

48. Aims • Evaluate herbal/natural product treatments that target disease outcomes and treatment- and disease-related symptoms. • Determine the effects of acupuncture on specific clinical symptoms in patients with cancer. • Quantify the biobehavioral effects of qigong and other mind/body-based interventions. • Examining the reliability and validity of TCM diagnostic techniques.

49. International Center of Integrative Oncology (ICIO) Established September 2003

50. Cooperation 7 TCM Clinical Trials Staff training • 2 Natural products • 4 Acupuncture • 1 Qigong