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Objective 2: Advance Research on the Whole Person and on the Integration of Complementary and Conventional Care

NCCIH 2021 Strategic Plan Objective 2

Central to the definition of whole person research are studies of integrated multicomponent therapies and interconnected systems. These address multiple aspects of a person and may involve diagnostic and therapeutic frameworks different from those of conventional medicine. Whole person research includes three components: exploring the fundamental science of interconnected systems, investigating multicomponent interventions or therapeutic systems, and examining the impact of these interventions on multisystem or multiorgan outcomes.

The current NCCIH portfolio includes research on natural products as well as mind and body approaches (both psychological and physical). Currently, much of the mind and body portfolio studies single systems (e.g., nervous system) while the natural products portfolio focuses more on outcomes involving multiple systems (e.g., digestive, metabolic, immune).

With this objective, NCCIH plans to support the development of methodologies to better understand how to study interconnected systems, how to investigate multicomponent interventions or therapeutic systems and their integration, and how to examine the impact of these interventions on multisystem or multiorgan outcomes.


Strategy 1: Promote basic and translational research to study how physiological systems interact with each other.

Over the years, much of the NCCIH research portfolio has evolved to become somewhat homogeneous⁠–⁠for example, research on meditation, mindfulness, and yoga, all of which remain important. However, exciting opportunities are emerging to carefully explore new paths toward whole person research. This will require both fundamental science and methods development using a range of approaches to address multiple aspects of a person or animal model. Mechanistic research may, as appropriate, study the impact of single or multicomponent interventions (experimental input or independent variables) on single or multisystem outcomes (output or dependent variables). Rigorous methods (e.g., factorial designs, principal component analyses) will be needed to support these variably complex study designs. The use of artificial intelligence to analyze multidimensional datasets offers exciting new opportunities that can be applied to whole person research, including identifying temporal changes in multisystem physiological patterns and defining the phenotypes of individuals more or less likely to respond to a treatment.

A comprehensive program in whole person research can collectively support a balance of analytical and synthetic approaches to elucidate individual mechanisms and understand how these mechanisms interact.

Strategy 2: Conduct clinical and translational research on multicomponent interventions, and study the impact of these interventions on multiple physiological systems (e.g., nervous, gastrointestinal, and immune systems) and domains (e.g., biological, behavioral, social, environmental).

NCCIH hopes to expand research on integrated multicomponent therapies. One challenge in clinical research on complex interventions is that researchers may want to tailor the interventions to specific populations, study individual components, or change the intervention to make it more convenient, but these modifications may make replication difficult and reduce the effect size of the intervention. It is important to have a reproducible intervention or algorithm of care that can be consistently delivered by different clinicians at different sites to conduct multisite trials to assess efficacy or effectiveness of the multicomponent intervention. Another challenge is how to power a study for multiple primary outcomes. NCCIH is also interested in the development of innovative strategies to evaluate multiple outcomes in a single trial.

Strategy 3: Foster multicomponent intervention research that focuses on improving health outcomes.

NCCIH-supported research has demonstrated that mind and body therapies are effective at improving symptoms in conditions such as pain and anxiety. While these therapies have shown promise, the efficacy of any single-modality treatment is typically modest, and finding a way to enhance the effect size of clinical outcomes is a crucially important goal. Multicomponent strategies may enhance the benefit to individuals by simultaneously targeting multiple pathways and may be more effective than a treatment used in isolation. It is also important to study multicomponent interventions that combine conventional and complementary approaches.

There is a fundamental lack of translational research on the mechanisms of resilience and health restoration in humans. In particular, the mechanisms of nutritional, psychological, and physical interventions in restoring health after an acute illness or recovery from a chronic condition are an understudied area that needs a multisystem approach to identify mechanisms and predictive biomarkers that could be used to optimize their effects. NCCIH seeks to support research that could expand the mechanistic and evidence base on complementary health approaches for preventing mental, emotional, and behavioral disorders and for promoting psychological and physical health, resilience, and health restoration.

Strategy 4: Conduct studies in real world settings, where interventions are routinely delivered, to test the integration of complementary approaches into health care.

NCCIH is particularly interested in studies on the efficacy and effectiveness of complementary and integrative health approaches aimed at managing pain, anxiety, and depression. The Center has invested in pragmatic research to study pain management.

Many research organizations, including NIH, support learning health care systems in which research is embedded into the delivery of care. In this type of system, data are collected every time a patient receives care, and over time, the system “learns” whether and how well the care worked. Whenever something is learned with this approach, it can be quickly applied and adopted.

Embedded pragmatic trials within a health care system are often challenging. Research and patient care have long been conceptualized as separate activities that take place in different locations under different types of oversight, and the types of recordkeeping used in clinical care, including electronic health records, may not always meet research needs. However, these challenges are beginning to be overcome, and innovative approaches continue to be developed allowing for informative research to be conducted in the actual settings where integrative health care is practiced. These approaches include pragmatic trials that employ rigorous experimental designs.

Given the widespread use of complementary health approaches, opportunities exist to employ clinical outcomes and effectiveness research methodologies to collect real-world evidence about the use of specific complementary approaches for health care, health promotion, resilience, and health restoration. This can include identifying the basic elements of health care systems that optimally support the implementation of a patient-centered, multicomponent approach to health care delivery. Pursuing this type of research requires creative collaboration with those who provide care in settings where integration of complementary health approaches could be studied. The real-world settings for such research could be quite varied, and may include schools, nursing homes, hospices, safety net clinics, Federally Qualified Health Centers, cancer treatment facilities, and settings that provide care for military personnel and veterans. NCCIH is continuing to build on initiatives such as the NIH Health Care Systems Research Collaboratory and the NIH–U.S. Department of Defense (DoD)–U.S. Department of Veterans Affairs (VA) Pain Management Collaboratory (PMC).

Story: Pain Research Supported by NCCIH Through Pragmatic Trials

Pain is the most common medical condition requiring treatment among military personnel. Studies report nearly 45 percent of active-duty military personnel and 50 percent of veterans experience pain on a regular basis, and there is significant overlap among chronic pain, post-traumatic stress disorder (PTSD), and persistent post-concussive symptoms. Data from the 2010–2014 National Health Interview Survey show that American veterans experience a higher prevalence of pain and more severe pain than nonveterans1. Although opioids are often prescribed to treat chronic pain, there is no evidence to suggest they are effective, and they are often associated with severe adverse effects and may lead to drug addiction, overdose, and death. Therefore, there is a need for nondrug approaches to complement current strategies for pain management and to reduce the need for, and hazards of, excessive reliance on opioids.

In 2017, NCCIH partnered with the DoD, the VA, and seven other Institutes and Centers at NIH to launch the NIH-DoD-VA PMC ( The PMC seeks to support the development, implementation, and testing of cost-effective, large-scale, real-world research on nonpharmacologic approaches for pain management and related conditions in military and veteran health care delivery organizations. The PMC is currently supporting 11 pragmatic, large-scale clinical trials. Of these trials, NIH is supporting six, the DoD is supporting four, and the VA is supporting one. Examples of interventions being investigated for their effectiveness in pain management include cognitive behavioral therapy delivered by phone, stepped-care management, behavioral health consultation in primary care, manual therapy such as chiropractic care, and percutaneous peripheral nerve stimulation. NIH is also supporting a coordinating center that provides technical, design, and other support to the research teams during this demonstration phase and will disseminate collaboratory-endorsed policies, best practices, and lessons learned from the demonstration projects.

All the studies supported by the PMC will not only assess if specific nonpharmacologic approaches are effective for pain management but also how they can be integrated into a health care system. For example, researchers at Yale University are investigating the effect of early resource education on pain management. The investigators in this study are enrolling veterans when they are seeking a disability classification for a pain condition and educating them on the different types of pain medications. In addition, they inform the veterans of the importance of treating both physical and psychological aspects of pain and connect the veterans with the services available to them. The researchers also assess their risk for substance use disorders and depression and refer the veterans to the appropriate treatment. If this intervention is successful, it can be quickly scaled up and made available nationwide to veterans seeking a disability classification. This early education and referral paradigm could also be adapted to other health care systems.

NCCIH is leading the NIH HEAL (Helping to End Addiction Long-termSM ) Initiative’s Pragmatic and Implementation Studies for the Management of Pain To Reduce Opioid Prescribing (PRISM) program, which seeks to take interventions and treatment guidelines that have already been shown to work for specific pain conditions and integrate them into health care delivery systems. Recent decades have seen an overreliance on the prescription of opioids for chronic pain, which has contributed to an epidemic of opioid overdose deaths and addiction. Research has shown that nonopioid pain management interventions can be effective for treating acute and chronic pain. More support is needed to assess the impact of evidence-based health care strategies and clinical practices and procedures when they are included in health care systems. Pragmatic and implementation trials could identify strategies to effectively implement evidence-based interventions and pain management guidelines.

As part of the NIH HEAL InitiativeSM, NCCIH is also leading the Behavioral Research to Improve Medication-Based Treatment (BRIM) program, which supports research that assesses whether behavioral interventions can improve outcomes of medication-based treatment. Specifically, the BRIM program seeks to test the effectiveness of combining medications with a wide range of evidence-based behavioral interventions in diverse groups of patients, including veterans, young adults, low-income individuals, and Latina and Native American women. The behavioral interventions include yoga and mindfulness, cognitive behavioral therapy, multidisciplinary rehabilitation, and mobile health technology. This study will determine whether using these interventions in combination with medication improves adherence to medication, improves treatment outcomes, and reduces relapse in individuals seeking treatment for opioid use disorder.

1Nahin RL. Severe pain in veterans: the effect of age and sex, and comparisons with the general population. Journal of Pain. 2017;18(3):247-254.