1. Whole Systems Research in Traditional Chinese Medicine (TCM) for Temporomandibular Dysfunction (TMD): Reflecting Clinical Practice in Research Cheryl Ritenbaugh, PhD, MPH, University of Arizona Mikel Aickin, PhD, University of Arizona Scott Mist, PhD, MAOM, Oregon Health & Science University Richard Hammerschlag, PhD, Oregon College of Oriental Medicine

2. 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.

3. 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

4. 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

5. 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

6. 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; WFP  5; 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

7. 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)

8. 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

9. 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

10. 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?

11. Baseline demographics (n=168) VariableValue Female (%) 87.5 Age: mean (SD)42.9 (12.7) Ethnicity (%) White Hispanic Other 86.7 10.3 3.0 Duration of pain (%) 0-5 years 5-10 years 10 + years 37.5 20.2 32.3

12. Most prominent TCM dx at baseline (n=168) TCM dxFrequencyPercent Liver Qi Stagnation 76 45.2 Qi & Blood Stagnation 70 41.6 Kidney Yin Xu 9 5.4 Liver Blood Xu 4 2.4 Spleen Damp 3 1.8 Kidney Jing Xu 2 1.2 Liver Yin Xu 2 1.2 Heart Xu 1 0.6 Spleen Qi Xu 1 0.6

14. Short-term Results Comparative Effects of TCM and Self-care TCM Effect (p-value) OutcomeBaseline (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) 5.90.46 (.212)0.58 (.065)0.58 (.022) *Average of worst facial pain, average when having pain, facial pain now

15. Distribution of TCM visits by participant (up to 20 within one year)

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

17. Distribution of follow-up data to 6 months post-TCM

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

19. 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…

20. Change in CFP on TCM: TCM first (solid) v. SC first (dashed) Pain score (2-6) Pain percent of baseline (100-50)

21. Change in CFP after TCM: TCM first (solid) v. SC first (dashed) Pain score (3-4.5) Pain percent of baseline (100-60)

22. 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

23. Acknowledgements

24. 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

26. Join the International Society for Complementary Medicine Research Go online at www.iscmr.orgwww.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

27. Long-term change in WFP as a function of initial pain levels from start of TCM 33.3 28.5 23.5 %%

28. Long-term change in CFP as a function of WFP levels from start of TCM 36.2 30.1 12.5 %%

29. Allocations to Treatment Groups at Weeks 2 & 10: Basis for Short-term Outcomes Wk 2: wfp  8 T/S wfp<8 (s) Wk 10 SC: wfp  5 T/S wfp<5 (s)

30. 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

31. 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

32. 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

33. Baseline co-morbidities of TMD pts (n=168) in present study # pt-reported medical conditions # pts

34. Baseline demographics (n=168) VariableFinding (%) Nature of Facial Pain Continuous Intermittent 49.7 50.3 Biosocial Impact Limits chewing Limits smiling / laughing Limits kissing Limits yawning 79.2 34.5 23.2 70.8

35. 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

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

37. Change in WFP on TCM: all Pain score (4-7) Pain percent of baseline (100-60)

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

39. Change in WFP on TCM: TCM first (solid) v. SC first (dashed) Pain score (2-8) Pain percent of baseline (100-50)

40. Change in WFP after TCM: T first (solid) v. SC first (dashed) Pain score (5-7.5) Pain percent of baseline (110-70)

41. 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?