20171022 R&D Strategies of Integrative Medicine and its Role in Elder Care by Dr. Lee Hyejung

1. Lee Hyejung, KMD, Ph.D
President of Korea Institute of Oriental Medicine
October 22, 2017
2017 Taiwan Global Health Forum

2. 1
Table of Contents
Introduction to Integrative Medicine02
Integrative Medicine for Elder Care03
R&D Strategies for IM04
KIOM Strategies for Elder Care05
Overview of Aging Issues in S. Korea01

3. 2

4. 3
Korea's population is aging rapidly
- There are 6.6 million people aged over 65 years, representing 13.2% of the population in
2015. This number is expected to reach 40.1% in 2060 (Statistics Korea, 2016).
- Korea's total birthrate was 1.25 in 2016, which is the lowest among the OECD members.
※ The total birthrate refers to the average number of children that a woman has or chooses to have over her lifetime
Aging Korea

5. 4
UnpleasantParadoxofAginginKorea
Longevity
Fragile
health
(disease
burden)
Poverty
(medical cost
burden)

6. 5
Rapid increase in life expectancy in S. Korea
- By 2030, Korean women can expect to live to 91 years of age. Korea is likely to become the
first country where life expectancy will exceed 90 years.(Nature, 2017)
Source: Am J Public Health, 2010
Korean men
Korean women
Long life

7. 6
Elderly in poverty
- S. Korea has the highest poverty rate for elderly citizens
among the OECD members
※ Almost half (48.6%) of South Korea’s population over 65 years lives
in relative poverty (the Guardian, 2017).
- S. Korea has one of the lowest net pension replacement rates
(45.2%), falling well below the OECD average of 65.9%
- An estimated 74% of poverty-stricken elderly Koreans live alone
- Many seniors decide to take their own lives to avoid becoming a burden to their families
※ High levels of isolation and depression have led to a dramatic rise in elderly suicide
No family support
Poverty and Social Exclusion
(source: the Guardian, 2017)
S. Korea USA Japan OECD
< % of elderly poverty, 2010 >
(source: OECD, 2011)

8. 7
Disease burden in the elderly population
- Older adults are at high risk for developing illnesses.
- Major health concerns for seniors include:
• Dementia and mental health concerns
• Diabetes and obesity
• Heart disease
• Cancer
- Elderly medical expenses accounted for 36.8% in 2015.
- The annual per capita medical cost by elderly (₩3,433K) is 3-fold larger than the average
(₩1,150K)
Source: Korean Journal of Pediatrics, 2002
Injury
Muscular-skeletal disease
Digestive disease
Respiratory disease
Cardiovascular disease
Neuro-psychiatric conditions
Diabetes
Cancer
<Cause of prevalent disease by age group in Korea>
Prevalentper100,000
Fragile Health Condition
(Source: National Health Insurance Korea)
Medical
expenses
Medical expenses
for elderly over age 65
medical expenses, Per
Capita,
by elderly over age 65
(Unit: ₩,
hundred million)
(Unit: ₩,
thousand)
Average annual
medical expenses for
65+ in S. Korea

9. 8
Aging is a multidimensional process encompassing all aspects of the mind
and body
Integrative medicine (IM) may be an
appropriate solution to prevent many diseases
related to aging
- it considers all factors that influence health, wellness and
disease, coupled with body, mind, spirit and community
IM helps improve quality of life for aging
individuals
Integrative Medicine is the Solution

10. 9

11. 10
Origin of Integrative Medicine (IM)
Origin of Integrative Medicine
- Originally, the term IM was born in an attempt to develop an educational course, “The
Program in Integrative Medicine” at the Univ. of Arizona. As part of the program, the
“Integrative Medicine Clinic” was established for the first time in 1994. (Tracy W., 1998)
3100 BC 2500 BC
Egyptian
medicine
Ayurveda,
Unani medicine
1600 BC
Traditional
Chinese
Medicine
800 BC
Greek
medicine
Roman
medicine
27 BC
Arabic medicine
622 AD
Thoth, ancient Egyptian
god often depicted as an
ibis-headed man.
Front cover of the book
“The Nectar of
Instruction 1st edition”
by A.C. Bhaktivedanta
Swami
Yin Yang Symbol
Hippocrates
Muhammed ibn
Zakariya al-Razi
Western
medicine
17th AD
Integrative
medicine
20th AD
(Pan W. et al., 2013)
(Richard P et al., 2015)
History of Medicines

12. 11
What is Integrative Medicine ?
Current definition of IM
The practice of medicine that reaffirms the importance of the relationship
between the practitioner and patient focuses on the whole person, is
informed by evidence, and makes use of all appropriate therapeutic
approaches, forms of healthcare and disciplines to achieve optimal health
and healing
(Developed and Adopted by The Consortium, May 2004 Edited May 2005, May 2009 and November 2009)

13. 12
“Integrative” vs “integrated”
- In Europe, it is called ‘integrated’ medicine and in the US ‘integrative’ medicine
“Alternative” vs “Complementary” vs “Integrative”
- Alternative medicine
Instead of, or at the exclusion of, conventional approaches (currently for non-evidence based
approaches)
- Complementary medicine
alongside with, or as an adjunct to, conventional approaches (collaborative)
- Integrative medicine
combining CAM, traditional, and conventional approaches in synergy
(combines all medical therapies, using optimum evidence and optimum research methodology)
Terminology Differences

14. 13
In fact, there is no standard IM definition
- It differs among countries, practitioners and scientists depending on medical
practices or cultural backgrounds.
- There are debates over what integrative care is and the nature of the
transformation of service.

15. 14
Difference by Country
In China, IM always refers to the Integration of TCM and WM (ITCWM)
- ITCWM is actively practiced in Chinese medicine departments in Western medicine-based
hospitals, all departments of Chinese medicine hospitals, and departments of IM hospitals
for various conditions
The integrative healthcare system in China was purposely created by Mao Zedong in 1956 “to integrate
the knowledge of Chinese medicine with the knowledge of Western medicine and pharmacology, to
create unique new medicine and pharmacology”
Conventional
medicine
J Integr Med. (2013) 11(2):135-139

16. 15
Difference by Medical Providers
Difference in Viewpoints b/w KM and WM stakeholders
- (KM stakeholders) IM makes use of all of the advantages of current medicines on the
basis of KM (IM is the concept of the expansion of KM’s medical boundaries)
- (WM stakeholders) IM combines conventional mainstream practices with CAM
Complementary
medicine
Western
medicine
“supportive”
“collaborative”
Korean
medicine
Western
medicine
Other traditional
medicines Complementary
medicine

17. 16
General Characteristics
Patient-centered
Selective
Holistic
Natural
Disease is understood to be the result of physical, emotional, spiritual,
social and environmental imbalance. Therefore, healing takes place
naturally when these aspects of life are brought into proper balance.
IM customizes treatment recommendations and
decision-making in response to patients’
preferences and beliefs. IM focuses on physical, psychological, spiritual,
social and lifestyle issues.
IM provides a greater
range of therapeutic
options to patients.

18. 17
Principles of IM
Donald Berwick
a former Administrator of the Centers for
Medicare and Medicaid Services.
President and Chief Executive Officer of the
Institute for Healthcare Improvement
1. Place the patient in the center
2. Individualize care
3. Welcome family and loved ones
4. Maximize healing influences within care
5. Maximize healing influences outside of care
6. Rely on sophisticated, disciplined evidence
7. Use all of the relevant capacities—waste nothing
8. Connect helping influences with each other
Berwick’s Model
(Source: Topics in Integrative Health Care, 2010)

19. 18
Patients and practitioners are partners in
the healing process
IM depends on a partnership between the
patient and doctor, where the goal is to treat
the mind, body, and spirit at the same time.
All factors that influence health, wellness,
and disease are taken into consideration,
including mind, spirit, and community, as
well as body.
Patients want to be considered whole human
beings in the context of their world.
Appropriate use of both conventional and
alternative methods (KM, CAM) facilitates
the body’s innate healing response.
IM recognizes the body’s profound healing
mechanisms and seeks to mitigate barriers
to healing by using nutrition, activity, mind-
body medicine, and where appropriate,
conventional and alternative therapies
Effective interventions that are natural and
less invasive should be used whenever
possible.
IM orders therapies ranking those that have
the greatest potential for benefit with the
least potential for harm first (acupuncture,
nutrition, exercise, etc.)
Good medicine is based on good science. It
is inquiry-driven and open to new
paradigms
Practical and pragmatic research models that
evaluate systems of care and investigate the
interaction of multiple health influences are
needed.
Practitioners of integrative medicine should
exemplify its principles and commit
themselves to self-exploration and self-
development
Alongside the concept of treatment, the
broader concepts of health promotion and
prevention of illness are paramount.
IM addresses the mind, body, and spirit with
an emphasis on supporting balance,
maintaining health, and promoting longevity
Integrative medicine neither rejects
conventional medicine nor accepts
alternative therapies uncritically
Weil’s Model
Andrew Weil
Clinical professor of medicine
at the University of Arizona
Principles of IM

20. 19

21. 20
Advanced
Cost-effective
Integrative
Medicine
IM is Balanced

22. 21
Why… IM for Elder Care ? (1/4)
The elderly often suffer from a mixture of acute and chronic medical
problems as well as functional disabilities.
Most seniors have a past medical history and presenting conditions
※ The elderly usually present multimorbidity due to chronic illnesses that are intermittently
aggravated by acute disease and exacerbated by pre-existing chronic illnesses
※ Approximately 80% of all people aged >65 years in the U.S. have at least one chronic condition,
and 50% have 2 or more (Ageing Res Rev, 2011)
-IM combines state-of-the-art conventional medicine with safe and effective
complementary therapies that are carefully selected.
-IM team care is provided by interdisciplinary collaboration in an attempt to
find the best combination of therapies for the needs of the elderly
IM offers a comprehensive, evidence-based, team-based, and well-
coordinated healthcare modality.

23. 22
IM offers gentler and safer approaches to address common health
conditions of seniors
-
The elderly are more susceptible to pharmaceutical adverse effects than
the younger population.
Seniors suffer more from side effects and complications, in part
because of their poor metabolism or excretion ability.
The health status of elderly individuals changes frequently and
dramatically, with those receiving care today potentially not receiving it
in the subsequent year, and vice versa.
- IM combines non-pharmacological or less invasive interventions when
appropriate.
Why… IM for Elder Care ? (2/4)

24. 23
IM offers patient-centered care
Healthcare providers are certainly aware of the differences between
medical problems of the young and old.
- Distinguished medical interventions for older patients are often ignored,
leading to inappropriate or incomplete treatment.
Older people are consistently excluded from clinical trials, even though
they are the largest users of approved drugs
Older patients deserve respect, but are neglected in reality.
- IM pursues optimized healthcare by treating patients with respect, courtesy,
and dignity
- Individual preferences and values are factored into the care plan, and all care
is aligned with patient preferences.
Why… IM for Elder Care ? (3/4)

25. 24
IM is actually “cost-effective”
- IM approaches can decrease the use of medications, resulting in substantial cost
savings for hospitals in regard to patient care.
※ Cost savings are achieved by reducing hospitalization and lowering the use of expensive medical
interventions. Instead, IM facilitates mind-body therapies, exercise, and nutritional approaches.
S. Korea has had the highest senior poverty rate in terms of income
among OECD member countries for several years
Cost is the most important factor in selecting medical options for the
elderly
(source: BJM Open, 2017) (source: EXPLORE: The Journal of Science and Healing, 2010)
Why… IM for Elder Care ? (4/4)

26. 25
Opportunities for IM for Elder Care
WELL-TIMED
INNOVATIVE
The conventional health
care system is in crisis
IM is an innovative medical
paradigm
IM use is constantly rising Older people are in favor
of non-conventional
medicine (ex. Korean
Medicine)
Senior dissatisfaction with
conventional medicine led to
the rise of IM approaches to
healthcare
The medical paradigm is shifting
from treatment-centered therapy
to disease prevention-centered
therapy.
68.7% of the population aged 60
and over use KM therapies in S.
Korea
(BMC CAM, 2017)
69% of S. Koreans have received
KM, and those who receive both
WM and KM are currently
increasing in numbers
EMERGENT
ENCOURAGING

27. 26
Common Barriers of IM Practice
• “The vast majority of studies have shown IM to be no different from placebo.”
(Tom Delbanco, MD, a Harvard Medical School professor)
• Many people have the impression that IM creates substantial add-on costs
Skeptical or
negative attitude
toward IM
Not enough
standardization
Not enough
scientific
evidence
• The absence of a standardized terminology and lack of a shared conceptual
framework is problematic.
• Due to differences between countries and manuscripts published in different
languages, extensive work is required to identify search terms and synthesize
findings
• The study of IM is costly, time-consuming, and methodologically challenging
(Maizes et al, 2002)
• Aging results from a number of causes. Despite extensive research, there is
no way to prevent aging.
• Many seniors use dietary supplements concurrently with medications. There
are raising concerns about harmful drug interactions.
Not enough
collaboration
• Little collaboration occurs between conventional- and non-conventional
practitioners
• Building trust and acknowledging different approaches are central to IM
practice

28. 27
Arnold S. Relman
Former editor-in-chief emeritus of the New
England Journal of Medicine
Professor emeritus of medicine and social
medicine at Harvard Medical School
Andrew Weil
Clinical professor of medicine
at the University of Arizona
“IM is not an advance, but a return to the past. I cannot
see how such an integration, even if it were possible,
would improve medical care or further the cause of human
health. Most alternative systems of treatment are based on
irrational or fanciful thinking and false or unproven factual
claims. Their theories often violate basic scientific
principles and are at odds….”
“In this country and throughout the world, patients in
unprecedented numbers are going outside of conventional
medicine to look for help. Why are people doing this?
Clearly, there is dissatisfaction with conventional medicine.
Dr. Relman has dismissed whole fields of medicine and
thousands of years of cultural tradition, such as Chinese
medicine….”
A Debate Between Arnold S. Relman and Andrew Weil

29. 28

30. Strengths Weaknesses
Opportunities
Threats
 Finding robust scientific
evidence
 Standardizing diagnostic
criteria
 Establishing a definite
concept for IM
 Standardizing R&D eligibility
criteria
 Setting priorities for the IM
research agenda
 Optimizing the appropriate
IM research framework
SWOTAnalysis(GeneralIMstrategies)

31. 30
① Establishing the IM Definition
Establishment of a Concept for Integrative Medical Treatment
- It is necessary to reach an agreement on a conceptual definition of IM
- A consensus concept is essential for IM development
R&D Strategy for Elder Care

32. 31
②SettingPrioritiesforResearchAgenda
Prioritization criteria should be established and addressed due to limited
R&D resources.
Considerable elements to determine the IM research priority
Those that impose a heavy burden of
suffering on individuals, families or the
community either because of their
severity
chronicity
prevalence
And for which current mainstream
therapies are unacceptable or insufficient
because of
lack of proven efficacy
substantial side effects
cost
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 occurs.
Criteria for conditions, diseases, and risky health behaviors with a high priority for integrative
health research (Explore 2010; 6:143-158)
R&D Strategy for Elder Care

33. 32
Quantity and quality of available
preliminary data to facilitate
determination
Public health importance of
the disease being treated
Cost of
research
Extent of use by the public
Appropriate type
of research
(low complexity of design,
repeatability of the
research design,
availability of the clinical
research infrastructure,
etc.)
(widespread and enduring use by
large segments of the population)
Recommended IM research criteria

34. 33
Documentation and description
of an unconventional treatment
Preliminary evaluation of safety
and efficacy on a small group of
subjects with a defined indication
Comparative evaluation of safety,
effectiveness and transferability
Research on the efficacy
and mechanism of action
Surveillance after acceptance in
anew clinical setting either as an
additional option for patients or
an integrated part of
conventional clinical practice
(Surveys, case studies or review of
the available literature)
(Observational, prospective, pragmatic
pilot study)
(Pragmatic multicenter RCT versus
conventional treatment or no treatment)
(Explanatory RCT, basic science research)
(Long term follow up, pharmacological
surveillance, risk-benefit studies)
③ Optimizing the Research Framework
R&D Strategy for Elder Care

35. 34
- Rational sequences of IM research are different from conventional and traditional medicine.
Step Conventional medicine Traditional medicine Integrative medicine
(1) Strong physio-pathological basis (‘‘it
could work’’)
Widespread and enduring use in
clinical practice (‘‘it seems to
work’’)
Strong requirements for
consideration of complete safety,
efficacy and better cost—benefit
(‘‘it needs something to work
better’’)
(2) Evaluation of safety and efficacy
(‘‘does it work in experimental
settings?’’)
Pragmatic evaluation of safety and
effectiveness (‘‘does it work in
clinical practice?’’)
Comprehensive evaluation of safety
and efficacy in synergy (‘‘does it
work better in experimental
settings?’’)
(3) Introduction in clinical practice;
evaluation of effectiveness (‘‘does it
work in clinical practice?’’)
Evaluation of efficacy; research on
the mechanism (‘‘Does it have
specific actions? why and how does
it work?’’)
Introduction in clinical practice;
evaluation of effectiveness (‘‘how
effective is it in whole person care?’’)
(Modified from Cardini F. et al., Complementary Therapies in Medicine (2006) 14, 282—287
Difference in the rational sequence between IM and Western medicine

36. 35
④ Finding Robust Scientific Evidence
- It is particularly important to illuminate which therapy helps and which does not
- Even identifying which one does not work can be valuable.
UCSC Research showed that saw palmetto did not improve benign
prostate hyperplasia, a noncancerous enlargement of the prostate
gland. More than 2 million men in the U.S. take saw palmetto as an
alternative to drugs. (The New England Journal of Medicine)
- Develop a leading medical treatment technology that overcomes the limitations of IM
practice and research
- Cutting-edge technology helps to better understand the comprehensive effects of integrative
therapies.
Searching for solid evidence is key
Application of advanced medical technology
R&D Strategy for Elder Care

37. 36
⑤StandardizingIMR&DApproaches
Research evidence of the effectiveness of IM should be built using a
standardized methodology and implemented using formal terminology
- Scientists should develop protocols to guide collaborative practices among different types of
practitioners and clarify their respective roles and responsibilities
- Single or shared clinical recording guidelines for accurate and rigorous reporting.
- Standardized clinical/critical pathways should be developed in each practice setting.
R&D Strategy for Elder Care

38. 37

39. 38
KIOM(KoreaInstituteofOrientalMedicine)
 KIOM: A government-supported research institute as a KM R&D hub
1994 Established in
Seoul, S. Korea
2004 Moved to Daejeon,
S. Korea
2009 Constructed the
Guam-
building(Laboratory)
2011 Designated as WHO
Collaborating Centre
for Traditional
Medicine
2012 Established Korean
Medicine Standard
Center
2015 Establishment of
KM Application
Center in Daegu, S.
Korea
 KIOM History
 Main functions
- R&D on KM and establishment of infrastructure for KM technologies
- Implementation of its role as a national stronghold for KM

40. Development of
herbal medicine for
aging-related diseases
39
Development of KM-
based prevention and
management system of
diseases
Development of drugs
for the prevention and
treatment of geriatric,
chronic, and intractable
diseases
Establishment of evidence for
the efficacy and safety of KM
clinical practice
Illumination of the
scientific basis of
KM theories and
principles
Procurement of KM
knowledge resources for its
practical utilization
Technology development
for disease prevention
and treatment for
centenarians
Technology development
for promotion of the value
of KM demands in the
clinical field
Establishment and
implementation of
sustainable KM
healthcare services
KIOMR&DStrategies&IMAssignments
KIOM’s particular R&D approach
KIOM R&D
strategy
Research and
development for the
concomitant
administration and
combinatory effects
of herbal and WM
IM’s Infra-Establishing
Research for Acquiring
Evidence on
Postoperative Care
Related
assignments
Development of sophisticated
technology for further
utilization of medicinal herbs
Procurement of KM
knowledge resources for its
practical utilization
Technology
development for
securing herbal
medicinal
resources
Development and
mechanistic studies of
herbal medicine for
senile cognitive
disorder improvement

41. 40
Development of herbal medicine for aging-related diseases
•Development of drugs for skin aging control
•Efficacy evaluation of herbal medicine for NAFLD (nonalcoholic fatty liver disease)
•Research on biological activity based on the mode of action
Technology transfer
Upfront 260,000$
Running 3.3%
NOVAKMED (subsidiary company)
NOVAREX (mother company)

42. 41
Development and mechanistic studies of herbal medicine for senile
cognitive disorder improvement
• Tremendous demand to cope with the expansion of the drug market for senile cognitive disorders
owing to the aging society
•Development of KM-based drugs for senile cognitive disorders, such as Alzheimer’s disease
• MoA (Mode of Action) identification of KM for senile cognitive disorders
Inhibition of amyloid-β
aggregation
Neuroprotective effect
Ameliorating effect on
memory impairment
Neuronal marker expression in
Alzheimer’s disease animal model
In vitro
In vivo

43. 42
Integrative Medicine Infra-Establishing Research for
Acquiring Evidence on Postoperative Care
•Clinical evaluation of IM clinical studies for postoperative care
•Development of clinical pathways for IM based on KM and WM
•Efficacy evaluation of KM for postoperative care

44. 43
Research and Development for Concomitant Administration of
the Combinatory Effect of Herbal and WM
•Symptom relievers, such as common cold drugs, have been prescribed by both WM
and herbal doctors in Korea. Unfortunately, the best case scenarios have not been
studied due to concerns about the harm or risk caused by herb-drug interactions.
•The KIOM challenges the beneficial side of herb-drug interactions, such as the synergy
or sparing effect, which are worthy of study under the country’s guidelines of fixed-dose
combinations.
• Herbal medicine, but not MTX, showed distinctive inhibitory
activities toward TNF-alpha, IL-1, and PGE2.
• They could be presented as independent mechanism
between the two. • The optimal combination ratio and dose range were
found

45. 44
Holistic
Therapies
Energy
Medicine
Alternative
Medicine
Korean
Medicine
Complementary
Medicine
Manipulative
Therapies
Surgery
Functional
Medicine
Pharmaceutical
Drug
Mind/body
Medicine
IMisRealAdvancedMedicine

46. Thank you!
Hyejung Lee
hjlee@kiom.re.kr
+82-42-868-9402