RESEARCH ON INTEGRATIVE HEALTHCARE: CONTEXT AND PRIORITIES
Gary Deng, MD, PhD,1,#Wendy Weber, ND, PhD, MPH,2Amit Sood, MD, MSc,3and
Kathi J. Kemper, MD, MPH4
It is important that integrative healthcare research be con-
comprehensive, and holistic healthcare that focuses on well-
being as well as disease management, and that the research itself
be well understood. The scope of this research extends beyond
evaluation of specific therapies, to include evaluations of multi-
modality whole system intervention, practitioner-patient rela-
tionships, patient goals and priorities, promoting self-care and
resilience, personalized diagnostic and therapeutic measures,
practitioner well-being, the comparative effectiveness of differ-
ent educational and outreach strategies in improving health and
healthcare, and the environmental/social causes and conse-
quence of health and healthcare. In this paper, we describe the
needs, and opportunities offered by cutting-edge research tools.
We propose a framework for setting priorities in integrative
health research, list areas for discussion, and pose a few ques-
tions on a future research agenda.
Key words: Integrative health, integrative medicine, comple-
mentary and alternative medicine, holistic, whole system, re-
search, research priorities
(Explore 2010; 6:143-158. © 2010 Elsevier Inc. All rights reserved.)
based, patient-centered, comprehensive, and holistic healthcare
that focuses on patients’ priorities for well-being, as well as
preventing, managing, rehabilitating, and palliating diseases
and injuries. The scope of research for integrative healthcare
as discussed in this paper is not only the evaluation of specific
complementary and alternative medical (CAM) therapies for
safety and effectiveness in treating specific medical problems
(the Institute of Medicine published its report Complementary
and Alternative Medicine in the United States in 20051), it also
includes multidisciplinary whole system intervention, partic-
ipant-centered evaluations of therapies and health practices,
clinician-patient interaction, patient goals and priorities,
health values and meaning, self-care, the comparative effec-
tiveness of different educational and outreach strategies in
promoting optimal health and healthcare, environmental fac-
tors and social policies affecting health, and system factors
affecting availability of resources that promote health, health
behaviors, or healthcare. Research must also address patient-
centered care in the context of family, culture, and commu-
nity. The research agenda for integrative medicine is by na-
ture broad and comprehensive, rather than being focused
solely on the effects and mechanism of selected therapies. In
this paper, we describe the state of science of integrative
medicine research, research needs, and the opportunities of-
fered by cutting-edge research tools. We propose a framework
for setting priorities in integrative medicine research, list areas
for discussion, and suggest a few questions for the research
CONTEXT: STATE OF THE SCIENCE, RESEARCH
NEEDS, AND INTEGRATION WITH CUTTING-EDGE
Study design. Integrative health researchers embrace the random-
method helps reduce multiple sources of bias. Although RCTs are
often viewed as the gold standard, it is not possible to conduct
RCTs for every research question due to logistic, economic, or
ethical concerns. Because many health practices and complemen-
with strong preferences for a particular therapy or practice may be
unwilling to consent to randomization. Furthermore, although
pharmacologic therapies are typically developed for one specific
indication (eg, antihypertensive effects), many integrative therapies
have multiple effects (eg, meditation may decrease blood pressure,
vary even among patients within a single diagnostic group. Al-
though the strongest conclusions and inferences can be reached
when there is concordance between research using different meth-
ods (eg, RCT, quasi-experimental, and prospective cohort), such
concordance is not always found (eg, the different conclusions
antioxidant supplements to prevent cancer,4or decreased risk of
dementia/cancer in patients using statins5). Observational studies
have provided important insights, such as the role of smoking,
1 Memorial Sloan-Kettering Cancer Center, New York, NY
2 Bastyr University, Kenmore, WA; currently at National Center for
Complementary and Alternative Medicine, Bethesda, MD
3 Mayo Clinic, Rochester, MN
4 Wake Forest University School of Medicine, Winston-Salem, NC
# Corresponding Author. Address:
1429 First Avenue, New York, NY 10021
© 2010 Elsevier Inc. All rights reserved.
EXPLORE May/June 2010, Vol. 6, No. 3
of different kinds of cancer, lipids and coronary disease, hyperten-
sion and stroke, and sleeping position and sudden infant death
syndrom.6Researchers need to recognize that different kinds of research
Integrative healthcare provides opportunities for innovative re-
search designs. Patient-centered care implies active patient partici-
pation in prioritizing outcomes and selecting therapies. Similarly,
community-based participatory research involves community
members in identifying research priorities and developing meth-
ods. Likewise, research in integrative healthcare optimally involves
its participants in identifying the most important outcomes and
empowers them to choose whether to be randomized (or not) to a
particular therapy. Research employingconcurrentRCTsandquasi-
experimental designs to evaluate therapies for low back pain has
enriched our understanding of the impact of patient preferences
for innovative research paradigms such as participant-centered research;
Outcome assessment tools. Optimal health in integrative medi-
cine refers to a state of well-being of the whole person: physical,
specific symptom or reversal of a specific disease process.12,13For
emotional, spiritual, and social outcomes,14such as instruments
used in rheumatology,15neurology,16,17geriatrics,18,19rehabilita-
tion,20,21pain, and palliative care.22,23Research in integrative
healthcare would also rely on broad functional measures such as
those developed through the NIH PROMIS project,24as well as
disease-specific measures. These measures form a broader, more
comprehensive and meaningful foundation for building personal-
ized yet global outcome measurement systems.
Another important aspect in outcome measurement is the
role of the patient or study participant. In patient-centered care,
what patients perceive is equally, or perhaps more, important
than what physiological parameters tell us. Participant-centered
integrative health research incorporates individual participant
preferences in considering appropriate study outcomes.25The
value of patient-reported outcome measures is recognized in-
creasingly by the medical community.26,27Integrative health
researchers can incorporate previous knowledge into their own
studies and develop new methods, as needed, tailored to their
own practice models.28-30
Application of information technology. The impact of infor-
mation technology on integrative medicine is enormous. Easy
on the Internet via search engines such as Google and Wikis
plays a large role in patients’ senses of empowerment. This de-
centralization of information makes practitioners not the sole
and frustrates patients. On the other hand, information technol-
capacity as a communication tool in many ways.
1. E-mails and text messages improve communications be-
tween providers and patients.31,32Do e-mail communica-
tions encourage patient’s stake in self-care, facilitate timely
management of emerging medical problems, or reduce un-
necessary utilization of healthcare resources? Do e-mail/text
message communications help monitor patient responses
and adverse events, improve adherence, and refine patient-
centered outcome evaluation in clinical studies?
2. Online support groups, bulletin boards, chat rooms, blogs,
and social network sites are frequented by patients to ex-
change notes on their diseases and healthcare providers.
These media can be used to learn patients’ perspectives and
evaluate, advise, monitor, and support them in optimizing
health outcomes. They also serve as a venue to recruit a large
number of patients to research studies.
3. The raw computing power available to researchers has made
certain previously impossible research feasible now. This is
most obvious in bioinformatics and personalized medicine.
Information technology enables the processing of the astro-
nomical amount of information generated from genomic
studies and the establishing of links between genomic varia-
tions and clinical outcomes.
4. Image processing technologies can be used to standardize
and quantify some of the diagnostic techniques in tradi-
5. Web 2.0 technology36provides a social, collective and col-
sharing, and reuse.37When expanded beyond the research
community, it also presents a platform in education to other
healthcare providers and the public.38,39
6. Finally, artificial intelligence has potentials in contributing
to whole system research.40,41Many traditional medical sys-
tems rely on pattern recognition for diagnosis. Application
of artificial intelligence in the recognition of those patterns
may represent empirical knowledge on clinical manifesta-
tions of some yet nondelineated pathophysiological links.42
A large number of epidemiological studies have assessed the use
tinued collection of this data is essential to further understand-
ing of the field.45,50-53Research describing integrative medicine
training and clinical programs (including how they were estab-
lished, the services offered, and the training and research
projects they are conducting) is emerging.53-55
It would be beneficial to the field if a standardized survey
could be created to gather data about CAM and integrative
medicine use, including benchmarks such as the use of conven-
tional therapies or care. This may be the most efficient way to
collect descriptive data about integrative medicine’s utilization,
cost effectiveness, and the characteristics and satisfaction of the
individuals who use it. Continuation of the alternative medicine
144 EXPLORE May/June 2010, Vol. 6, No. 3Integrative Medicine Research
supplement to the National Health Interview Survey56is a min-
imal requirement to maintain an understanding of the utiliza-
tion of CAM in the United States. Efforts should be made to review
and trends in the field, such as including questions specifically about
integrative medicine, CAM treatments, and conventional care recom-
mended by licensed clinicians, lay providers, and family/community
Basic Science Research
Mechanistic studies of specific CAM modalities. Mechanistic
studies have begun to elucidate biomedical mechanisms to ex-
plain clinical effects of CAM therapies. For biologically based
therapies such as botanicals, the research generally identifies the
iological pathways through which those constituents affect
physical systems.57-59However, the complex composition of
greater total activity than individual constituents.60-63Studying
such as standardization and quality control, unknown active
constituents, multiple potential biological targets, and complex
interactions among the constituents.64,65Newer experimental par-
adigms are needed to assess the differential effects of complex mixtures
versus simple compounds. Similar to conventional pharmacotherapy,
this research needs to also take into account the effects of secondary me-
tabolites of botanicals on biological materials.
Mechanistic studies of energy medicine, manipulative prac-
tices, and mind-body therapies involve delineation of the phys-
iological pathways modulated by them (eg, the interactions
among behaviors, the conscious mind, the autonomic nervous
system, hormones, and immune functions).66,67Through such
research, the relationships between stress and disease, especially
stress and immune function, are being explored.68-72The neu-
roendocrine stress response and immune systems have a bi-
directional relationship that can affect susceptibility to in-
flammatory diseases. Individual variability in neuroendocrine
responsiveness may contribute toward the efficacy of mind-
The brain plays a central role as a target of stress and stress
therapy. Neuroplasticity, a dynamic process that constantly al-
ters the neurochemical, structural, and functional components
of the nervous system related to experience, would be a worth-
while target to study with mind-body interventions. Some of the
examples of the effect of mind-body approaches on brain struc-
ture include the increase in prefrontal cortex volume following
cognitive behavioral therapy in patients with chronic fatigue syn-
drome74and increase in prefrontal cortex and right insula volume
with meditation.75The role of neurotrophins, particularly brain
derived neurotrophic factor as a mediator for neuroplasticity, is
beginning to emerge and needs to be further characterized with
respect to mind-body intervention.76The brain is a malleable or-
gan, and the lack of resilience may be a key aspect of anxiety and
mood disorders as well as other systemic problems.
Like psychotherapy, many behavioral and mind-body interven-
tions require active patient participation, which cannot be repro-
duced in animal studies. Advances in functional neuroimaging
technology, such as functional magnetic resonance imaging or
positron emission tomography, can demonstrate changes in activ-
ity in regions of the brain in real time and enable us to study the
complex neuronal matrix involved in real-world emotional and
social experience.77The technology has been used to study mind-
body therapies or energy-medicine modalities in recent years.78-83
The specific neurobiological changes that might mediate the
placebo effect could offer innovative therapeutic insights.84The
efficacy of placebo effect on enhancing frontal modulation of
nociceptive sensory and/or affect processing and individual
variability in placebo responsiveness as a predictor of efficacy
of mind-body interventions is an interesting area for future
Because physiological pathways are increasingly understood
to be nonlinear and multidimensional, traditional laboratory
approaches tend to be too simplistic to capture the complexity
of real clinical situations. Advanced mathematical and statistical
modeling techniques will be important to advance research in
the complex systems of integrative medicine. Sensitive and non-
invasive methods that can measure multiple biomarkers are
likely to help identify pathways that may be selectively affected
by different interventions.87,88
Application of genomic science to personalized healthcare. Some
technologies developed in genomic sciences can be harnessed to
enhance integrative medicine research, in particular toward per-
sonalized healthcare. Genomics refers to the study of all the
genes of a cell, or tissue, at the DNA (genome), mRNA (transcrip-
tome), or protein (proteome) levels. It is well known that individ-
uals respond differently to risk exposure and interventions.
More knowledge of the DNA sequence of the human genome
and the function of individual genes and their variants makes it
possible to identify individuals at risk for a particular medical
condition or responsive to a particular intervention.
Variations at nearly 100 regions of the genome have been
associated with an increased risk for diseases with a complex
genetic background, such as diabetes, inflammatory bowel dis-
ease, cancer, and heart disease.89Genetic variants in nicotinic
receptor genes were found to be linked to nicotine dependence
and smoking behavior, which may explain why some patients
are particularly resistant to smoking cessation measures.90,91
Individuals respond differently to nutrients, and nutrients affect
gene expression (nutrigenomics).92Individuals with one genetic vari-
ant of an intestinal fatty acid–binding protein gene have signifi-
cholesterol and apolipoprotein B when consuming a diet rich in
soluble fiber.93Better understanding of nutrigenomics would help
us in understanding the “individuality” of one’s response to bioac-
shop to review the state of nutritional genomics research and to
provide guidance for further development and translation of this
knowledge into nutrition practice and policy.95
The ever expanding database in pharmacogenetics helps us un-
derstand why individuals respond quite differently to the same
biological intervention. Differences in response to drugs or di-
etary supplements may also come from varied metabolism from
polymorphism in drug-metabolizing cytochrome P450 en-
Integrative Medicine ResearchEXPLORE May/June 2010, Vol. 6, No. 3
sive metabolizers may have markedly increased risk of side ef-
fects, whereas poor metabolizers would experience poor efficacy
of the drug.97
Epigenetics refers to the study of heritable changes in gene
function that occur without a change in DNA sequence.98Such
changes can occur via mechanisms such as DNA methylation,
to provide high-resolution reference epigenome maps and speed
progress in epigenetic research (the Alliance for the Human
Epigenome and Disease).102Epigenetics takes into consider-
ation the effects of the environment on gene expression patterns
that can be passed along to daughter cells, setting the stage for
disease preventive interventions to have a lasting effect. These
findings may lead to novel cancer prevention strategy that acts
early in the cancer pathogenesis process,103including use of
botanical agents or nutritional approaches.104
Although these technologies are exciting and promising, they
are expensive and require additional development before their
results can be translated into effective clinical care. At this point,
at a level of confidence only for a handful of diseases.Much work
based on genomic technologies.
jority of CAM clinical trials have evaluated single components
depression, a specific set of acupuncture points for headaches, a
protocol of chiropractic adjustments for low back pain, or mel-
atonin for insomnia). It is beyond the scope of this paper to
provide a summary of all the clinical trials conducted in the
field. In some cases, there have been enough studies on a partic-
ular treatment and condition to result in a systematic review or
more than 600 articles related to complementary therapies as of
November 2008. Readers are referred to those reviews for a
summary of findings in clinical trials.105-112
(including conventional therapies such as surgery and psycho-
therapy) are difficulty with blinding and providing a credible
control intervention. Some of the approaches that used surgery
and psychology that might be applicable include blinding par-
ticipants to the study hypothesis, use of sham training ap-
proaches, sham procedures, similar attention-control interven-
tions, and blinding of outcome assessors.113
Incorporating elements of the CONSORT statement for the
nonpharmacologic treatments in designing trials may be help-
well as outcomes related to participant priorities, safety, and social/
economic outcomes will increase the strength of the evidence even if the
study can only be designed as a single-blind (investigator) trial. Inves-
tigator neutrality may be particularly challenging for studies of
nonpharmacologic interventions because part of the treatment ef-
fect may be related to the context and process of care, such as that
ent study designs (RCT, single-blind trials, quasi-experimental de-
sign, retrospective cohorts) can strengthen conclusions and en-
hance generalizability of results while providing rich information
about the impact of patient and provider expectations and beliefs
Identification and inclusion of generalizable molecular mark-
ers that have been correlated with functional measures (such as
inflammation and stress) and are responsive to treatment (such
as telomerase activity and telomere maintenance capacity in
human immune system cells improving with stress manage-
ment) increase the credibility of study findings and provide ob-
jective surrogate outcome measures.116,117
A challenging issue in studying biologically based therapies,
such as dietary supplements, is securing a consistent study agent
with multiple and sometimes unknown active constituents.118
Careful selection of the study population, endpoints, and sam-
ple sizes are also crucial for success. Structured, well-thought-out
approaches need to be developed so that limited resources are optimally
used to test interventions with a high potential for efficacy,119particu-
larly in light of several recent expensive negative trials with dietary
Attention needs to be paid to the scope and overall design of
the study with the intent to balance internal validity with exter-
nal generalizability. For dietary supplements, phase I/II trials are
helpful for establishing optimal formulations, dosages, and safety before
embarking on expensive phase III trials.125,126For mind-body, energy-
based, and manual interventions, initial focus on creating a structured
and reproducible intervention consistent with how they are practiced in
real life along with an appropriate control group would be worthwhile.
Combining data for a meta-analysis can be particularly chal-
lenging in the field of integrative healthcare. For example, there
are hundreds of forms of Qi gong, and each is used traditionally
for different reasons; there are several traditions of acupuncture
and many different needling techniques; herbal preparations
can vary greatly depending on the growing conditions and ex-
is subject to debate.
Whole system research and multimodality studies. A new
trend in integrative health research is the push for whole systems
research, which strives to examine the effect of a multimodality
healthcare approach to provide individualized treatment, since
this will more accurately evaluate the healthcare that is currently
being provided to patients. There are several commentaries in
the literature urging integrative medicine researchers to consider
research methods beyond the RCT.127-130For example, Riten-
baugh et al131examined the effect of whole system Traditional
Chinese Medicine versus naturopathic medicine versus usual
care for treating temporomandibular disorders.
Several investigators have discussed the need to use more
complex methods of analysis so that these systems of healthcare
can be examined, rather than the efficacy of each part of the
system.130,132,133Some suggest using network and complex sys-
tem analysis as methods for assessing whole systems research.
However, it is critical for researchers interested in these methods
146 EXPLORE May/June 2010, Vol. 6, No. 3Integrative Medicine Research
to work with skilled biostatisticians experienced with these more
complex statistical methods.132Verhoef et al133encourage re-
searchers to add qualitative measures to studies because they can
provide a source of data for unexpected outcomes and a way to
measure the broader effects of a whole system, such as integrative
Beyond Therapeutic Clinical Trials
Individual resilience and hardiness. Of the three variables in
the triangle of disease causation (agent, host, and environment),
host factors remain suboptimally addressed. Alternative medical
systems consider strengthening the host as a primary focus. Re-
silience and hardiness refer to positive abilities and skills of an
individual in response to stress and adversity.134Exposure to
stress and traumatic events is common, but, not all of those
exposed develop posttraumatic stress disorder or other negative
health outcomes. Hardiness is correlated with positive health
outcomes.135-137Individual aspects of resilience are also associ-
ated with positive outcomes.138,139For example, greater pre-
event internal locus of control prevents posttraumatic stress dis-
order in women giving birth140and maintains treatment gains
for patients with posttraumatic stress disorder. Resilience is thus
an important concept in the fields of physical, mental, and spir-
physical and emotional illness in the face of stress, to identify optimal
strategies in developing resilience within integrative medicine, and to
identify social factors that can be modified to support hardiness to pro-
mote public health.
Social factors and practitioner-patient relationship. Social
support enhances resilience and improves many diverse health
improved survival in the elderly.145,146The effect of social sup-
port on physical health and longevity may be mediated through
life, better access to resources, improved use of resources, posi-
tive effects on the immune system, a sense of engagement, and a
greater feeling of purpose.147-150Practitioners can offer mean-
ingful social support that enhances health outcomes.151,152
When individuals become a caregiver of a family member with a
chronic disease, it is important to assess the strain and burden of
tain wellness of the caregiver.153-155
Integrative medicine emphasizes the importance of the rela-
tionship between practitioner and patient to achieve optimal
doctor-patient relationship and the process of care (eg, access,
length, practice patterns, cost). There has also been substantial
research in related areas such as social support,158,159communi-
clinical encounters (eg, individual vs group; in person vs tele-
phone or internet),170-172patient satisfaction,173-175trust,176,177
and team building and shared governance.178,179To date, little of
this research on the processes of relationship-based care has been synthe-
research on acupuncture now often includes placebo needles,
but has not examined closely the process of building the rela-
tionship between therapist and patient or compared the pro-
cesses of care provided by acupuncturists with that provided by
practitioners; nor have comparisons been made about the rela-
tionships among team members on traditional medical multi-
disciplinary teams (eg, clinician, nurse, social worker, physical
therapist, occupational therapist) with integrative teams (eg, na-
turopathic practitioners, nutritionists, acupuncturists, massage
Self-care, behavior change, adherence. One of the most im-
portant issues in healthcare is how to best inspire, motivate,
empower, and facilitate self-care. Self-care includes both pro-
cesses and action capabilities.180The processes include life ex-
perience, learning processes, and ecological processes. Action
capabilities include power and performance capabilities.
The primary aim of inspiring, motivating, and empowering
patients is toward a single goal—improving health through pos-
itive behavior change. Several models have been developed to
address behavior change. These include models based on attach-
ment theory,181the chronic care model,182,183the extended par-
allel process model,184the health belief mode1,185,186the prob-
lem-solving model,187,188the self-management model,189,190
social cognitive theory,191,192the transtheoretical model,193,194
and the theory of reasoned action.195,196Ideally, clinical coun-
seling incorporates several essential components for successful
behavior change. Most of these models were developed to ad-
dress a single specific medical condition. Behavior change models
need to be tested within the context of multiple, concurrent, common,
complex medical conditions.
Comprehensive, integrative treatment recommendations,
even for patients with a single diagnosis, involve lifestyle modi-
fications as well as medications, resulting in complex, multifac-
eted treatment plans.197Although most research on adherence
has focused on medications, little is known about the impact of
combining advice about medications with advice about other
practices or therapies on adherence to the pharmaceutical regi-
men. Lifestyle counseling appears to increase patient satisfac-
tion, but its overall impact on cost of care and adherence is
largely unknown.198,199Furthermore, adherence to specific rec-
ommendations may vary according to patients’ explanatory mod-
els.200For example, patients who believe their hypertension is
related to stress may be more adherent to recommendations
about stress management, whereas patients who believe their
blood pressure is purely a genetic or biochemical problem may
be more adherent to pharmaceutical regimens.201Different ex-
planatory systems could have dramatically different impact on
patients’ willingness to embark on or adhere to different treat-
ment regimens. Research is needed on how to best match patients’
mismatching on adherence, clinical outcomes, satisfaction with care,
and cost of care.
Integrative Medicine Research EXPLORE May/June 2010, Vol. 6, No. 3
The global village–social determinants and consequences of
health. Integrative healthcare looks beyond individual health
affecting health. Research has begun to establish the critical role
of the environment on human health.202-205Research will play
an important role in determining the most effective, efficient,
and equitable strategies for translating new knowledge about
environment into integrative clinical practice. Providing con-
ventional healthcare also impacts the environment (eg, pharma-
ceuticals contaminating drinking water supplies; biological and
technical waste disposal; and incineration of mercury, polyvinyl
chloride, and other products), which in turn affects human
health.206-211There is strong evidence that stress adversely af-
fects health; yet little research has addressed ways in which
healthcare institutions can effectively improve their environ-
ment, reducing stress for both clinicians and patients to achieve
optimal healing environments. Social support mitigates the per-
nicious effects of many stressors, yet there has been little system-
atic research on the most cost-effective strategies to improve
social support for patients, family members, clinicians, or staff
within healthcare institutions, or the impact of such changes on
tive healthcare providers and institutions can reduce their adverse envi-
ronmental impacts and promote positive healing environments while
providing high-quality affordable, effective, comprehensive, patient-cen-
Advances in media, communication, commerce, and trans-
portation technologies have resulted in well-documented changes
in health behaviors (eg, decreases in fruit and vegetable intake,
increases in sedentary behavior), access to health information and
ing, international travel for surgical procedures, telemedi-
cine)212-218and professional education. Integrative medicine
has been a leader in providing online courses.219-221Research is
needed to determine the most cost-effective and equitable strategies to
provide integrative medicine and health education using modern tele-
communications, including telephone, the Internet, webinars, and tele-
conferences for both individual and group models.
Social policies also profoundly affect health. Integrative
health, as a holistic discipline, must include research to better under-
stand the impact of public policies on overall health. Little research
has been conducted to evaluate the health consequences of
variations in social policies about agriculture, transportation,
education, or energy. Such studies might include regional
comparisons in the United States, or comparisons of the ef-
fects of policy variations between countries and over time, on
broad health outcomes.
Public policies that affect payments for certain kinds of
osteopathy, doctors of chiropractic) and a few kinds of therapy
(prescription drugs and surgery) versus policies promoting pay-
ment for fitness club memberships, massage, nutritional supple-
on health outcomes. The current reimbursement schemes in the
not improve much and continue to return frequently for medica-
munication skills, stress reduction coaching, lifestyle coaching,
the absence of policies supporting their financial viability. Thus,
research is needed regarding the effective translation of knowledge about
the environment and behavior into effective social policies and reim-
SETTING PRIORITIES FOR THE INTEGRATIVE
HEALTHCARE RESEARCH AGENDA
Framework to Set Priorities
Given the large number of research areas that need to be ad-
dressed, and limited resources, a systematic approach to priori-
tizing projects is needed. A model has been proposed that in-
and a comprehensive view of important outcomes.222
Conditions. Priority should be given to conditions and diseases
that satisfy the criteria in Table 1, those that impose a heavy
for which integrative approaches offer a reasonable likelihood of
being helpful and are already in use. Examples include anxiety;
asthma; attention-deficit disorder; back pain; cancer; cardiovascu-
lar diseases and stroke; chronic and severe pain syndromes; depres-
sion; developmental disorders, including autism; insomnia; obesi-
and autoimmune disorders; and addictive disorders.
Therapies. Therapies requiring additional professional inter-
vention are also priorities for research because of the substantial
costs associated with professional care. Thus, research on the
effectiveness, safety, and costs of chiropractic, acupuncture, elec-
Table 1. Criteria for Conditions, Diseases, and Risky Health Behav-
iors With High Priority for Integrative Health Research
Those that impose a heavy burden of suffering on individuals,
families or the community either because of their
And for which current mainstream therapies are unacceptable or
insufficient because of
● lack of proven efficacy
● substantial side effects
● lack of availability
And for which integrative health offers a reasonable likelihood of
being helpful based on
● proven safety in animal models
● lengthy historical use or compelling results from case reports,
case series, epidemiologic studies, case-control trials or cohort
studies, or clear scientific rationale
And for which widespread use by families and/or clinicians already
148 EXPLORE May/June 2010, Vol. 6, No. 3Integrative Medicine Research
troencephalographic biofeedback, hypnosis, or other mind-body
techniques requiring licensed professional therapists should be
high priorities.223-225Research on interventions (eg, certain natural
of preliminary data and are on the verge of definitive evidence for
widespread clinical application should also be prioritized, as such
research is likely to be a high-yield investment.
Types of research: synthesis. Given the frequently conflicting
data from medical research studies, overviews and data synthe-
sizing analyses are critically important for translating research
into practice. The Cochrane Collaboration and others have
made important contributions to this field over the last 10 years,
clinicians, policy makers, and researchers is needed.226-229
Outcomes. Outcomes include not only traditional measures of
morbidity, mortality, cost of care, and patient satisfaction, but
also the impact of care on family cohesiveness, cultural identity,
spiritual beliefs, resilience, coping, and self-efficacy, as well as
clinician competence, burnout, quality of care, and impact on
outcomes (Table 2). The impact on the environment, and social
address the concept of health as optimal functioning rather than as the
absence of disease and to address patient priorities, particularly when
there are multiple coexisting outcomes of interest.
The following are specific areas of research for discussion in
Spectrum of Life Cycle
Integrative healthcare can be provided to patients across the
demographic spectrum of age, gender, and race/ethnicity. There
may be disparities in the availability and quality of services to
different populations.230Integrative care can also be provided
for prevention, and acute and chronic illness, as well as rehabil-
itation and palliation. Among the most vulnerable populations
that have been least studied are children and adolescents and
patients suffering from genetic or congenital disorders. Other
include women across the life cycle, including those who are
pregnant, breast-feeding, in different phases of the menstrual
cycle, or at menarche and through menopause; the frail elderly;
patients with complex conditions and multiple comorbidities;
patients at the end of life; those with limited access to care;
and patients from diverse cultural/ethnic backgrounds. It is also
important to study how different therapies and practices differ-
entially affect diverse individuals (age, gender, race/ethnicity,
culture, socioeconomic status).
With the development of large integrative clinics across the
United States, epidemiological methods can be used to generate
outcomes data on their patients to allow for prospective stu-
dies of integrative medicine for “The Outcomes Research
Project.”231In addition to outcomes data, it would be useful for
these clinics to create patient registries to gather data on the
specifics of the therapies and practices for each patient.
Comprehensive epidemiologic data are also important for
clinical research studies because CAM therapies and lifestyle
ies. For example, individual vitamins can impact all causes of
mortality.232-235On the other hand, some dietary supplements
can adversely interact with pharmaceuticals.236Accounting for
and minimizing possible confounding effects is not possible if
the data are not collected.
Table 2. Outcomes of Interest in Research on Integrative Health
● Mortality rates, years of life saved
● Morbidity: physical, mental, emotional, spiritual, and social
symptoms; severity of illness
● Health behaviors: dietary, exercise patterns; smoking, drinking,
drug use; unprotected sexual relations; sleep; stress
management; positive communication and relationships
● Healthcare use and costs, including self-care, complementary
and alternative medicine care, and conventional care
● Satisfaction with care
● Developmental milestones and behavior
● Activities of daily living
● Quality of life
● Costs associated with care
● Direct and indirect financial costs; opportunity costs of missed
treatments; side effects: symptomatic and asymptomatic organ
dysfunction, injuries, infection; adverse interactions with other
therapies; x-ray and other toxic exposures
● Days of work/school missed; delinquency, incarceration
● Days of work missed, out-of-pocket costs, impact on
● Psychosocial impact on families, emotional impact on sense of
● Coping, peace, serenity, harmony in relationships, a sense of
meaning or purpose in life, self-efficacy, self-esteem
● Divorce, employment, bankruptcy
● Sense of cohesiveness, cultural identity; social capital
● Cost to society, rate of malpractice suits
● Environmental impact: cost of remedy to society, environment,
(overharvesting of herbs leading to extinction; climate change;
● Provider satisfaction with role
● Burnout, sense of effectiveness and being part of healing
Integrative Medicine ResearchEXPLORE May/June 2010, Vol. 6, No. 3
Comparative effectiveness and health services research are
also high priorities.237,238Descriptive studies are needed to de-
termine how providers practice, what patients seek care from
integrative health clinics, the benefits they receive, and the cost
effectiveness of integrative care.128,129,237,238Before studying
the efficacy of individual components of integrative care, prag-
sive integrative care in the real-world setting in which multiple
of the scope of this kind of care are urgently needed.237
Basic Science, Mechanistic Studies
Taking mechanistic research to the extreme may lose sight of the
complex, interactive nature of human diseases and behaviors.
Integrative researchers should guard against this. On the other
hand, reductionist research is essential to understand the mech-
anisms of the effects of integrative care.
Among the areas that should be considered as priorities are
1. Genomic/proteomic/pharmacogenetic studies investigating
the individuality of patients, despite sharing the same diag-
nostic label. Such knowledge can be used to develop more
2. System biology studies to identify and characterize the in-
teractions between multiple components of the biological
processes and the interactions between mind and body. This
research could improve appreciation of the interconnected-
ness of various components in human health and lead to
3. Research on how behavioral interventions can change bio-
logical processes at the molecular and cellular level. This
would create more effective tools for further behavior mod-
ifications relevant to reversing human diseases.
4. Research on the brain’s role in physiological adaptation and
the effects of stress (eg, neuroimaging studies of adaptive
An area in need of further research is a critical assessment of the
many novel laboratory assessments intended for evaluation of
biomarkers indicative of disease risk, prognosis, or treatment
options. Because of the novelty of these tests, little or no data
exist about their sensitivity and specificity, making interpreta-
tion of results difficult. In some cases, the tests offered are not
diagnostic but rather informative of the individual, with their
clinical meaningfulness unknown. Until more research docu-
considered experimental and will not be reimbursed by conven-
tional insurance, limiting their availability to certain economic
Study design. The paradigm of pragmatic (effectiveness) versus
explanatory (efficacy) studies remains relevant for integrative
with few restrictions for enrollment, is still limited because the
complex variables that go into individual decision making can-
not be controlled in a clinical trials setting.241For research to be
generalizable, it is important to define the real-world contexts in
is the selection of appropriate outcome measures. Wherever pos-
sible, participants should help select meaningful outcome variables in
pragmatic trials.242The basic elements of study design and con-
duct need to be addressed adequately, as noted above.243Even
with a good study design, a single neglected issue could seriously
impact the validity of the results.244This highlights the rele-
vance of concurrent studies with different designs to help min-
imize potential limitations from one type of trial (eg, limited
enrollment in RCTs in which potential participants have ready
access to the therapy or practice outside the trial and have strong
preferences for one type of treatment). Researchers should partner
with practitioners and patients to develop and conduct community-
designs to minimize bias and maximize meaning and translation into
improved practice and policy while being mindful of the appropriate
stage of research (pragmatic vs explanatory).
Personalized and holistic healthcare. In a holistic view, many
in the narratives of many traditional medical systems. Systems bi-
models to explore other such connections based on genetic and
functional variables.132,133, 248
To emphasize patient-centered care, future integrative health
research should take advantage of technological advancements
to individualize intervention and outcome assessment.249Ap-
plication of pharmacogenetics knowledge to herbal medicine
trials may result in a better selection of the study population,
reducing sample size while increasing the effect size, leading to
more efficient use of research resources and minimizing the
number of falsely negative trials.250,251Computerized patient-
centered outcomes assessment networks would produce efficacy
endpoints. These endpoints should take into consideration pa-
tients’ priorities, be clinically relevant, and be consistent with
the goal of integrative health.252
Patients’ expectations and beliefs about therapies are intri-
cately linked to their explanatory models and sense of mean-
ing.253,254New methods and tools are being devised to assess
patients’ beliefs and attitudes, but these have not been widely
implemented.255-257Different practitioners’ expectations, be-
of diagnostic evaluations, counseling, and treatments offered to
patients.258-260In addition, patients may have different values
and priorities in addressing their symptoms, and attention to
these priorities may affect satisfaction with care and adherence
to recommendations.261The complex issues inherent in providing
patient-centered integrative care in the context of multiple conditions in
patients with different priorities, values, expectations, and beliefs are
poorly understood. It is possible that new research paradigms will be
needed to address this lack of knowledge, not only for clinical outcomes,
150 EXPLORE May/June 2010, Vol. 6, No. 3Integrative Medicine Research
on practitioners (eg, burnout and fatigue) and the public’s health (eg,
overall healthcare costs, impact on work/school, activities of daily liv-
Promoting self-care and resilience. To encourage health-en-
hancing behavior and promote self-care, integrative healthcare
relies on tools from psychological sciences, such as skills of
motivational interviewing.262Resilience can be enhanced
through use of mind-body modalities such as relaxation, hypno-
sis, visual imagery, meditation, yoga, Tai Chi, Qi gong, cogni-
spirituality. In addition, resilience can be reinforced through
spiritual practices such as cultivating compassion, forgiveness,
gratitude, and finding meaning and purpose to one’s life.263,264
Optimal disease management and healthy lifestyles including
nutrition, physical exercise, restorative sleep, and an optimal
environment are also likely to foster resilience. Interventions
primarily aimed to foster resilience are beginning to be tested in
clinical trials.265-268Early studies suggest that resilience might
correlate with selective activation of the left prefrontal cortex.269
This needs to be further validated. Effective strategies to promote
optimal individual and social behaviors and policies need to be devel-
oped and tested to foster sustained health improvements. Research into
(a) designing and testing resilience interventions incorporating the wis-
dom of traditional and indigenous healing systems and (b) further un-
derstanding of the neurobiology of resilience have the potential to trans-
Practitioner-patient interaction and partnership. Integrative
care entails incorporating biopsychosocial interdisciplinary con-
tent, emphasizing compassion, communication, mindfulness,
respect, and social responsibility.270A core aspect of such care is
the relationship between practitioner and patient,157,271(ie, re-
lationship-centered care). The two key skills for practitioners to
facilitate this relationship-centered care are to cultivate profes-
is beginning to be investigated. A high priority for future research is
comparative effectiveness of different educational and training strate-
ing relationship-centered care.
In a clinical trial, patients improve for multiple reasons. These
include spontaneous remission, natural course, regression to the
mean, biased reporting, nonspecific therapeutic effects, and spe-
cific therapeutic effects. The nonspecific therapeutic effect,
which may account for improvement in up to 60% of patients
for some of the conditions,273has been considered more a nui-
sance than a useful therapeutic effect because of the need to
control within the context of placebo-controlled trials for phar-
macologic treatments. However the efficacy observed in the
placebo arm may sometimes be significantly superior to no
treatment or standard medical care.274-277The skills of profes-
sionalism and humanism within an integrative encounter are
likely to increase this nonspecific effect.
Instead of considering the placebo effect as of secondary impor-
tance, it might be more apt to consider the placebo effect as “con-
textual healing,” or nonspecific psychoneuroimmunologic stimu-
lant, an aspect of healing that has been produced, activated, or
maximize contextual healing include the environment of the clin-
for it is likely to offer expanded tools and additional insight into
patient care. In situations where it is important to separate the
specific effect from contextual healing, optimal effort needs to be
placed toward validating a placebo control prior to pursuing large
RECOMMENDATIONS FOR ACTION
The ultimate goal of integrative health research is to guide clin-
ical practice and public policy to maximize health. When for-
mulating guidelines, two factors are critical: strength of evidence
and burden/risk to the patient. Because decisions must at times
need to be taken into account. Although the highest level of
evidence is desirable for every health intervention, it is simply
not possible to achieve this goal. Limited research resources
apies with high risk or burden (economic, time, and effort) de-
mand a high standard of evidence, often in the form of multiple
RCTs, to be utilized in clinical practice. Those with low- or little
risk/burden can be incorporated into practice even when the
highest level of evidence is not available.280Such an approach
can be summarized in a simple 2 ? 2 table (Table 3) about how
to decide whether or not to use a particular therapy based on
safety and effectiveness. Implicit in this model is the notion that
the clinician and patient both understand and agree on the
problem, the goal of therapy, the evidence regarding safety and
effectiveness of the therapy being considered, the extent to
which it is accessible, affordable, and that it is of high and
consistent quality, as well as similar information about alterna-
tive treatments (or a combination of treatments) under consid-
eration for this and possibly other problems or diagnoses.
tice and the issues discussed in previous sections, we make the
following recommendations for action regarding integrative
medicine research; key stakeholders need to be identified to
make it a collaborative, multidisciplinary effort for each item—
including researchers, patients, and policy makers:
Table 3. Benefit and Risk Ratio and Selection of Therapies
Integrative Medicine Research EXPLORE May/June 2010, Vol. 6, No. 3
● prioritize pressing areas of research in integrative medicine
and define the level of evidence required for their clinical
● establish a consortium of integrative medicine researchers to
form consensus on how to implement the research priorities
● build an international information technology platform that
communication between researchers to achieve synergy of
● conduct comparative effectiveness and cost-effectiveness re-
search to inform clinicians and policy-making bodies, espe-
cially in light of burgeoning healthcare cost to society, so that
more resources can be allocated to integrative medicine re-
● develop and evaluate new models of participant-centered re-
multiple, complex, chronic, common problems
We propose the following questions to be discussed:
1. What are the three most important research questions in
integrative healthcare as a whole?
2. What should be the top three research priorities in integra-
tive health in the setting of limited resources?
3. What progress would you like to see made in integrative
health research in the next three to five years?
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