National Center for Complementary and Alternative Medicine (NCCAM) staff are presenting in the following workshops at the International Research Congress on Integrative Medicine and Health. The congress is convened by the Consortium of Academic Health Centers for Integrative Medicine.
NCCAM staff names are in bold below.
Tuesday, May 13 (Pre-Congress Workshops)
Writing a Grant: Challenges in Clinical Trial Design and Important Statistical Considerations
Cynthia Long, Ph.D., Statisticians Working on Complementary and Alternative Medicine and Integrative Medicine Studies; Laura Lee Johnson, Ph.D., NCCAM
9 a.m.–12 noon
This workshop is intended to help participants in their grant writing efforts, with an emphasis on addressing important issues pertaining to clinical trial design, statistical considerations, and how to present a study proposal to grant, protocol, and manuscript reviewers. The introduction will discuss how CAM and integrative medicine trials are and are not different from other medical trials and the obstacles that these trials face. Though alternative study designs will be discussed, the focus will be on randomized, controlled clinical trials and the elements in designing such studies. We will identify those elements of the study design that grant reviewers focus on and expect to be in a grant proposal. We will also discuss statistical considerations such as sample size and identifying an appropriate statistical consultant for grant proposals. A practicum conducted in small groups will focus on refining clinical trial designs submitted by former participants and/or proposed by workshop teachers. This workshop will help researchers, in particular research trainees, fellows, and junior faculty, in their grant writing efforts—with an emphasis on important issues pertaining to a statistician’s role on collaborating in grant writing, how to find and effectively collaborate with a statistician and data manager, critical issues that need to be addressed, and what reviewers look for in the research strategy section.
From Idea to Project: Career Development Strategies
Alberto Rivera-Rentas, Ph.D., Emmeline Edwards, Ph.D., Catherine Bushnell, Ph.D., Wendy Weber, N.D., Ph.D., M.P.H., Peter Kozel, Ph.D., NCCAM
9 a.m.–5 p.m.
The proposed workshop reaffirms NCCAM’s long-standing commitment to research training and the development of a well-prepared diverse biomedical workforce and its alignment with its strategic objective four: Improve the Capacity of the Field To Carry Out Rigorous Research. The workshop theme is the development of an independent investigator and the presentations will focus on successful career development strategies. Activities will provide an overview of the process of conceptualizing a project that: (1) meets NCCAM guidelines, (2) fits the Center’s research priorities, (3) is aligned with NCCAM’s strategic plan, and (4) supports the Center’s mission. Speakers at different career stages will share their experiences and paths to become independent research investigators. This day-long workshop will also include a working lunch session for participants to meet with NCCAM’s staff and program officials representing different scientific areas, which will allow time for exchange of ideas and onsite guidance.
Wednesday, May 14
NCCAM’s Strategic Priorities for Funding Clinical Trials
Wendy Weber, N.D., Ph.D., M.P.H., Emmeline Edwards, Ph.D., Kristen Huntley, Ph.D., Dale Birkle Dreer, Ph.D., Robyn Bent, R.N., B.S.N., NCCAM
A significant proportion of NCCAM’s extramural research portfolio includes clinical research projects and, specifically, clinical trials. Similar to other National Institutes of Health (NIH) institutes and centers, NCCAM wants our clinical research portfolio to reflect the Center’s current strategic priorities in allocating funding resources where they can be most impactful with rigorous clinical designs. In the last year, NCCAM has critically examined the clinical research portfolio and developed a strategy to encourage clinical trials that align with NCCAM’s priorities. This symposium will provide an overview of the challenges NIH and NCCAM have encountered with funded clinical trials, including participant recruitment and retention, costs, inadequate timeframe, and failure to publish. Presenters will describe the range of clinical trials that investigators can pursue from intervention refinement, to efficacy studies, to dissemination and implementation of effective treatments. NCCAM’s priorities for clinical trials will be highlighted. NCCAM program officials will describe the available funding opportunities for clinical trials and the process for submitting large clinical trials. The NCCAM review officer will provide an overview of the review criteria that are applied to clinical trials. The presentation will help the audience determine which funding opportunity is the best fit for the stage of research (and the level of evidence) they are proposing. A representative from the Office of Clinical and Regulatory Affairs will discuss available resources for planning and implementing clinical trials, including NCCAM’s Clinical Research Toolbox and the NCCAM onsite clinical monitoring program. Ample time will be reserved for a panel discussion to answer questions about the overall NCCAM strategy for clinical trials.
NIH Pain Consortium—Standards for Research on Chronic Low-Back Pain
Partap Khalsa, D.C., Ph.D., NCCAM; Anthony Delitto, Ph.D., P.T., FAPTA, University of Pittsburgh
A critical issue for advancing research on chronic low-back pain (cLBP) is the challenge of comparing results from the many classes of interventions. NIH Pain Consortium workshops on cLBP noted that prior clinical studies have often used variable criteria for determining inclusion/exclusion, varying case definitions for low-back pain, and inconsistent baseline assessments, stratification criteria, and outcome measures. Hence, it has been challenging to compare studies of similar or competing interventions, replicate findings, pool data from multiple studies, resolve conflicting conclusions, develop multidisciplinary consensus, or even achieve consensus within a single discipline regarding interpretation of findings. A key recommendation from the NIH workshops on how to advance cLBP research was to establish research standards on cLBP. The NIH Pain Consortium convened a Research Task Force that, through a series of meetings, has crafted a set of research standards that includes the following: 1) definition of cLBP; 2) classification of cLBP by level of impact; 3) minimum dataset for NIH-supported cLBP research comprising assessment of: medical history, physical examination, diagnostic testing, self-report of functional status, psychosocial factors, and mood disturbance; 4) supplemental data for specific situations; 5) outcome recommendations; and 6) recommendations for research on the proposed standards. These research standards will be required by NIH for future research grant applications submitted on cLBP.
Thursday, May 15
Conducting Pragmatic Trials With Complementary and Integrative Interventions: Lessons Learned
Wendy Weber, N.D., Ph.D., M.P.H., Partap Khalsa, D.C., Ph.D., Laura Lee Johnson, Ph.D., NCCAM; Jeffery Dusek, Ph.D., Penny George Institute for Health and Healing, Allina Health; Lynn DeBar, Ph.D., Kaiser Permanente Center for Health Research; Jason Gerson, Ph.D., Patient-Centered Outcomes Research Institute (PCORI)
10:30 a.m.–12 noon
In the last few years there has been a growing interest by the public and the scientific community in clinical trials that will test research hypotheses, which will directly inform the health care system. This interest has been driven by a number of factors including the high cost of traditional efficacy studies and the exclusion of many individuals from efficacy trials, resulting in results that do not generalize to many patients. This symposium includes presentations that will provide definitions of pragmatic and comparative effectiveness research (CER) studies, and describe circumstances when these study designs are appropriate. NCCAM and PCORI representatives will highlight an overview of funding opportunities and priorities for pragmatic and CER studies. Two investigators will present an overview of ongoing pragmatic research studies. One is designed as a prospective observational study design conducted within a hospital care system utilizing electronic health records to gather outcome data. The second study is a cluster randomized pragmatic trial examining treatments for chronic pain in multiple health care systems. Presenters will discuss an overview of the challenges encountered in conducting these studies and how they have overcome these challenges. The final presenter will be a statistician who will provide a summary of the statistical and data quality concerns that need to be addressed in pragmatic studies including: sites needed for cluster randomization, data quality in electronic health records, and confounding and bias in observational designs. The session will close with a panel discussion with all presenters to answer questions from the audience.
Peer Review, or How To Prepare Competitive Applications
Peter Kozel, Ph.D., Dale Birkle Dreer, Ph.D., Martina Schmidt, Ph.D., Hungyi Shau, Ph.D., NCCAM
The peer review process is an essential step in the path NIH and other funding sources follow to identify and select grant applications for funding. The evaluative meetings at which the scientific merit of applications is assessed are usually closed to the public. However, understanding the peer review process, its outcomes, and how to respond to those outcomes are key skills for investigators to master if they wish to become successful applicants. This workshop will use the NIH peer review process as a model to provide participants with an inside perspective on the review process and guidance on preparing competitive grant applications to NIH and other funding sources in a highly challenging funding climate. Aspects addressed include: a description of the review process; differences in review criteria between different mechanisms; timelines for preparing and submitting applications; common applicant mistakes and how to avoid them; and guidance on how respond to previous reviewers’ comments in your revised application. Recent changes and updates to the NIH application and review processes will also be discussed. Participants will leave this workshop being better prepared to develop and submit competitive grant applications to NIH and other funding sources. This workshop is relevant to scientists and clinicians at all career stages, from graduate students submitting individual fellowship applications, to full professors and deans submitting multicomponent center grants.
Friday, May 16
Practical Considerations in Planning and Implementing Individual and Group Intervention Studies: Strategies That Can Help (or Hurt) Scientific Rigor
Qian Li, Sc.D., Laura Lee Johnson, Ph.D., Robyn Bent, R.N., B.S.N., Wendy Weber, N.D., Ph.D., M.P.H., Christine Wishnoff, NCCAM
10:30 a.m.–12 noon
Study teams strive for rigorous study designs to address research questions despite numerous challenges. While it may appear simple to plan a randomized, controlled, double-blind study, implementation can be challenging. Based on implementation challenges commonly noted in trials of yoga, tai chi, meditation, and whole systems studies, this workshop will guide attendees through the study design and implementation process, and assist in the recognition of common pitfalls. It starts by proposing a series of research questions and discussing several study design options such as group, cluster, or individual level randomization; interactions between the study team, participants, and intervention delivery; and basic statistical considerations including intent-to-treat or per protocol analysis populations and missing data. Attendees will work in groups to define a study question, hypotheses to test, and study design strategies. Choices made by the groups will determine the potential study planning and implementation problems that the groups will encounter on their path to successful study completion. The small groups will then be challenged with an implementation hurdle such as difficulties recruiting, retaining, blinding, or randomizing participants; differential participant retention and followup; or other issues with study conduct. These challenges will be shared with all the workshop attendees to get feedback and additional perspectives through guided discussion. At the end of the workshop, choices for final study design and determination of which questions can be answered based on that design will be shared with workshop attendees. This will be a highly interactive and engaging session sharing creative and best practices in addition to lessons learned across communities. Upon completion of the workshop, participants and presenters should have an expanded perspective on potential study implementation and interpretation issues and potential solutions that can be used in designing their own studies, reviewing study proposals, evaluating the literature, and developing new research recommendations.
Spotlight on Rigorous Study Design, Reproducibility, and Transparent Reporting
Emmeline Edwards, Ph.D., David Shurtleff, Ph.D., Carol Pontzer, Ph.D., NCCAM
Developing effective complementary and integrative interventions for symptom management is central to the mission of NCCAM. To accomplish its mission, NCCAM relies on and supports a diverse preclinical and clinical research grant portfolio. The reproducibility of such research, however, has been questioned and, most recently, the spotlight has been on the irreproducibility of preclinical research. This session will highlight these concerns and the likely causes. It will provide possible solutions for improving the design, execution, and reporting of preclinical studies, basic human mechanistic studies, and Phase I clinical studies that serve as the foundation for translating basic research discoveries into improved clinical practice and health. Dr. David Shurtleff will summarize recent concerns and possible causes for preclinical research irreproducibility. He will describe steps NIH and other organizations, such as scientific journal publishers, are taking to address this problem. Dr. Emmeline Edwards will discuss the need for a core set of reporting standards for basic human mechanistic studies with a special emphasis on data handling. She will highlight practices related to data handling that can lead to false positives, such as interim data analysis, ad hoc exclusion of data, retrospective primary end-point selection, sample size determination, and adequacy of control conditions. Dr. Carol Pontzer will describe some negative and inconclusive NCCAM-sponsored natural products intervention trials to exemplify the importance of rigorous foundational research, evaluation of scientific premise, and analysis and interpretation of clinical trials data. She will also comment on efforts by scientific journals and reviewers to ensure quality of publications through the enhancement of review guidelines.
Probiotic Nutritional Pharmabiotic Interventions of the Brain-Gut-Microbiota Axis: A Systems Biology View
Linda Duffy, Ph.D., NCCAM; John Bienenstock C.M., M.D. (Hon), FRCP, FRCPC, FRSC, McMaster University; Kristen Tillisch, M.D., UCLA Medical Center
Gut microbiota are increasingly recognized as influencing many aspects of human health. Emerging evidence suggests that the gut microbiota also influences brain function and may have a role in anxiety, mood, and cognitive behaviors, neurophysiology, and neurochemistry. The abundance and complexity of symbiotic host-microbial interactions contributes to the fitness of human well-being under varying ecologic conditions. Whether this translates to microbial-based central nervous system nutritional and biotherapeutic interventions remains an intriguing possibility and one that is worthy of much further investigation. For example, commensal strains of bacteria in animals has been shown to reduce anxiety and change the presence and activity of receptors in certain brain regions that are associated with anxious and depressive-like behaviors. A unique view of the symposium is the emerging ecologic and systems biology perspective available with novel cellular- and molecular-based technologies. Preliminary evidence suggests that administration of selected keystone eco-stabilizers as probiotic interventions can also modulate various aspects of brain function, some of which are vagus dependent. Ingestion of lactic acid bacteria (LAB) selected strains can decrease anxiety and reduce stress-induced increases of plasma corticosterone levels in mice. LAB strains also have been shown to alter the mRNA expression of GABA and GABA receptors in several brain regions. These preliminary findings suggest that parasympathetic innervation is necessary for probiotic effects to functionally alter select microbiota-brain interactions. However, the strains with the most translational impact need to be carried out longitudinally in randomized, controlled safety studies under tight regulatory INDs to examine if there are systematic changes that correlate with anxiety, stress, and other brain behavior conditions.
Advancing the Use of Population-Based National Survey Datasets Including Data on CAM Use in Children
Christina Bethell, Ph.D., M.P.H., M.B.A., Child and Adolescent Health Measurement Initiative/Oregon Health and Science University; Barbara Stussman, NCCAM
This workshop provides resources, technical tips, and applied examples to expedite and enhance the valid and meaningful use of the Complementary and Alternative Medicine (CAM) Supplement of the National Health Interview Survey. Qualitative and quantitative approaches to the survey’s development, design, and data collection will be discussed, and the content and methodological features of the survey dataset will be described. To provide a platform to translate these data into knowledge and action, free user-friendly online tools for accessing data, datasets, and resources will be demonstrated. An interactive group activity will draw upon real world examples to show potential research uses of the dataset and online tool. The workshop will promote use of the national survey among CAM researchers and advocates by describing the depth, breadth, methods, and features of the survey, as well as the functionality of data access and technical assistance resources.