Whole Systems Research in Traditional Chinese Medicine (TCM) for Temporomandibular Dysfunction (TMD): Reflecting Clinical Practice in Research

Cheryl Ritenbaugh, PhD, MPH, University of ArizonaMikel Aickin, PhD, University of Arizona

Scott Mist, PhD, MAOM, Oregon Health & Science University

Richard Hammerschlag, PhD, Oregon College of Oriental Medicine

Whole Systems Research

The goals of Whole Systems Research

(WSR) are to assess and compare real-

world, multi-modality systems of care

in which the research reflects unique

features of the intervention theory and

therapeutic context.

Temporomandibular Dysfunction (TMD)

Presents as a spectrum of

dysfunction

– Localized: pain in face, jaw, neck,

head, shoulders

– Systemic: Multiple co-morbidities,

including fibromyalgia, depression,

headache, sleep and GI disorders

Complexity of TMD warrants whole systems approach to compare real-world treatment

options • NCCAM P50: Phase I/II pilot RCT of

Traditional Chinese Medicine (TCM), Naturopathic Medicine (NM) and Dental Specialty Care (SC) for TMD– Ritenbaugh et al JACM 2008;14(5):475-87

• Provided necessary information for Phase II whole systems trial design– Entry criteria– Inclusion TCM diagnoses (basis for herbal IND)– Need for standardized self-care arm– TMD class important for all– Longer time window needed for treatments

TCM for TMD: Main Aims of Phase II Study

1. To further develop methods to evaluate real-

world TCM for pts with TMD and specified

TCM diagnoses compared to self-care therapy

2. To implement a randomized, stepped-care

phase II trial of TCM and/or Self-Care (SC – a

validated psychosocial intervention) among

pts with elevated pain

TCM for TMD: Design

– NCCAM U01 dual site trial (n=80/site)• Univ Arizona (Tucson), PI: Cheryl Ritenbaugh, PhD, MPH• OCOM (Portland), PI: Richard Hammerschlag, PhD

– Stepped-care comparison of whole systems: TCM and “Self Care” (pain clinic model)

– Pt population• Inclusion criteria: m/f 18-70; WFP5; TMD dx;

one of 8 TCM dx; willing to remain non-pregnant• Exclusion Criteria: unwilling for allocation or

acupuncture; acupuncture in past 6 months, ever for TMD; meds with known herb interaction; TMD surgery

TCM for TMD: Design

– Outcome measures• WFP & Characteristic pain (short- and long-

term)

• Pain interference with activities

• Pt experience via qualitative interviews

• Other: AIOS/global health/decreased co-morbidities

– Challenges• FDA (IND and lab work for safety reasons)

• R01 U01 (OCRA/NCCAM)

TCM Protocol– Up to 20 acupuncture visits over 1 year;

patients’ choice of timing

– Treatment based on TCM diagnosis-specific treatment guidelines

– Practitioner calibration of diagnoses (Mist et al,

JACM 2009;15(7):703-9)

– Acupuncture (up to 20 needles per session)• Listed points for TMD; by TCM dx;

• Px flexibility for tailoring to co-morbidities

– Herbs• Formulas for each TCM dx from 67-herb FDA approved

list

• Px flexibility to adjust for side effects, dx

Self-Care Protocol

• TMD Class – 2 hrs (part of run-in)– Basic information on etiology, physiology, and prognosis

of TMD

– Basic self-care techniques

• First 8 weeks: validated Self-Care intervention– Protocol-based self-care training; manual, workbook

– 2 x 1.5 hr visits; 3 x 30 min phone calls

– Basic self-care: symptom monitoring, stress management, specific techniques

• Subsequent 8 weeks: Time and attention control– Resiliency: lay Cognitive Behavioral Therapy -- materials

developed for this study

– Same schedule as first 8 weeks

Study Objectives• Short-term

– Does TCM offer greater benefit than Self Care for pts with high pain levels?

• Long-term– Does TCM provide benefit to patients over the long

term? At what levels?

– Is benefit from TCM (if found) maintained post-tx?

– Do patients who start with Self Care receive added long-term benefit relative to those who receive only TCM?

• Other– Does a stepped-care research design make sense as a

model of real-world care?

Baseline demographics (n=168)Variable Value

Female (%) 87.5Age: mean (SD) 42.9 (12.7)

Ethnicity (%)White

HispanicOther

86.7 10.3 3.0

Duration of pain (%)0-5 years5-10 years10 + years

37.520.232.3

Most prominent TCM dx at baseline (n=168)TCM dx Frequency Percent

Liver Qi Stagnation 76 45.2Qi & Blood Stagnation 70 41.6Kidney Yin Xu 9 5.4Liver Blood Xu 4 2.4Spleen Damp 3 1.8Kidney Jing Xu 2 1.2Liver Yin Xu 2 1.2Heart Xu 1 0.6Spleen Qi Xu 1 0.6

Short-term ResultsComparative Effects of TCM and Self-

care TCM Effect (p-value)

Outcome Baseline (mean)

Wk 2 wk 10 (pts to TCM or SC

at week 2)

wk 10 wk 18 (pts to TCM or SC

at week 10)

Total

Worst facial pain 8.5 -0.28 (.528) -0.85 (.024) -0.58 (.045)

Characteristic facial pain*

6.3 -0.41 (.310) -0.79 (.033) -0.62 (.023)

Social activities 3.3 -0.21 (.689) -1.34 (.001) -0.81 (.016)

AIOS (overall well-being)

5.9 0.46 (.212) 0.58 (.065) 0.58 (.022)

*Average of worst facial pain, average when having pain, facial pain now

Distribution of TCM visits

by participant (up to 20

within one year)

Change in CFP on TCM: allPain score (2-6) Pain percent of baseline (100-50)

Distribution of

follow-up data to 6 months

post-TCM

Change in CFP after TCM: allPain score (2.5-4) Pain percent of baseline (100-65)

What is the effect of combining self-care and

TCM?

Comparison of long-term outcomes for those randomized

at first point to self-care or TCM…

Change in CFP on TCM:TCM first (solid) v. SC first (dashed)

Pain score (2-6) Pain percent of baseline (100-50)

Change in CFP after TCM:TCM first (solid) v. SC first (dashed)

Pain score (3-4.5) Pain percent of baseline (100-60)

Conclusions/Lessons learned

• TCM can help TMD patients achieve clinically

meaningful improvement in Characteristic Facial Pain

• This improvement in CFP continued up to 6 months

beyond the last TCM visit

• The combination of self-care with TCM may improve

long-term outcomes

• 8 practitioners across 2 sites can implement a flexible

protocol

• As a design, ‘stepped-care’ made researchers happy

but did not please patients

Acknowledgements

Acknowledgements

• Richard Hammerschlag (Portland PI)

• Mikel Aickin (design and analysis)

• Scott Mist (TCM protocol, IND, practitioner training

& calibration (Mist et al, JACM 2009;15(7):703-9) )

• Sam Dworkin (TMD expert; SC intervention)

• Mark Nichter (qualitative design)

• Charles Elder, Ed Paul (medical directors)

• Cheryl Glass, Josh Metlyng (management)

• Emery Eaves, Liz Sutherland (interviews)

• Partap Khalsa (& Richard Nahin), NCCAM

• Steering Committee/DSMB

National Center for Complementary and Alternative MedicineNational Institutes of HealthU.S. Department of Health and Human Serviceswww.nccam.nih.gov

This work is supported by a cooperative agreementgrant from

Join the International Society for

Complementary Medicine Research

• Go online at www.iscmr.org• The website finally works (we think…)• Save the date: May 15-18, 2012

– International Research Congress on Integrative Medicine and Health, Portland OR

24

68

10

1 2 3 4 5 6St udy Follow-ups on TCM

WFP 1-4 WFP 5-7 WFP 8-10

M ean +/ - St andar d Deviat ion of t he M ean

Wors t Fac ial Pain by Value at Bas el ine

Long-term change in WFP as a function of initial pain levels from

start of TCM

33.3

28.5

23.5

%

02

46

8

1 2 3 4 5 6St udy Follow-ups on TCM

WFP 1-4 WFP 5-7 WFP 8-10

M ean +/ - St andar d Deviat ion of t he M ean

Charac teris tic Fac ial Pain by WFP at Bas el ine

Long-term change in CFP as a function of WFP levels from start of TCM

36.230.112.5

%

Allocations to Treatment Groups at Weeks 2 & 10: Basis for Short-term

Outcomes

Wk 2: wfp8 T/S wfp<8 (s)

Wk 10 SC:

wfp5 T/S wfp<5 (s)

Complexity of TMD warrants whole systems approach to compare real-world treatment

options • NIH P50: Phase I/II pilot clinical trial of Traditional Chinese Medicine (TCM), Naturopathic Medicine (NM) and Dental Specialty Care (SC) for TMD– Ritenbaugh et al JACM 2008;14(5):475-87

• Individual tailoring of care in each arm (n=50) – TCM: Acupuncture, Herbs, Tuina, lifestyle

counseling– NM: Herbal/nutritional supplements, physical

medicine, stress management, exercise techniques

– SC: Bite splints, pain management, self-care counseling, referrals to physical therapy, bio-behavioral therapies

TCM, NM, SC for TMD: Results Ritenbaugh et al JACM 2008;14(5):475-87

• TCM and NM > SC for reducing in-treatment worst

facial pain (WFP), the primary endpoint

• TCM>SC for reducing average pain (also prim e/p)

• Clinically meaningful reduction in WFP ( 30% from

baseline) by end of tx and 3-month post-tx:

% of pts: SC (18,27); NM (28,34); TCM (32,46)

• Conclusion: WSR design can be implemented

Lessons learned to guide phase II trial• Need to clarify I/E entry criteria, e.g. pain

level• Pts willing to accept randomization• Identified TCM diagnoses for TMD• Identified commonly used herbs (basis for

IND)• Usual care comparison was too variable• WFP correlated with other pain measures• Pts reported…

– TMD class was useful– Longer time frame desired for treatments– Measurement burden

Baseline co-morbidities of TMD pts (n=168) in present study

# pt-reported medical conditions

# pts

Baseline demographics (n=168)

Variable Finding (%)

Nature of Facial PainContinuousIntermittent

49.750.3

Biosocial ImpactLimits chewing

Limits smiling/laughingLimits kissing

Limits yawning

79.234.523.270.8

TCM for TMD trial design

• SC assigned to those doing well at week 2

• Balanced randomization* to TCM or SC at

weeks 2 & 10 for pts doing less well

*based on WFP, gender, age, depression

• Once on TCM, always on TCM

• Short-term outcomes: baseline vs. wks 10 &

18

• Long-term outcomes: through 18 months

Long-term results:Weeks from first to last TCM visit

Change in WFP on TCM: all

Pain score (4-7) Pain percent of baseline (100-60)

Change in WFP after TCM: allPain score (4.5-6.5) Pain percent of baseline (100-70)

Change in WFP on TCM:TCM first (solid) v. SC first (dashed)

Pain score (2-8) Pain percent of baseline (100-50)

Change in WFP after TCM:T first (solid) v. SC first (dashed)

Pain score (5-7.5) Pain percent of baseline (110-70)

Other analyses in progress

• TCM pattern distribution: change over time

• TCM pattern relative to outcome

• Px variability in tx plan (point selection, herbs)

• TUC/PDX differences (relative to climate?)

• Who does best on which tx?