The Journal of Pain, Vol 13, No 11 (November), 2012: pp 1075-1089Available online at www.jpain.org and www.sciencedirect.com

Comparative Effectiveness of Traditional Chinese Medicine and

Psychosocial Care in the Treatment of Temporomandibular

Disorders–Associated Chronic Facial Pain

Cheryl Ritenbaugh,* Richard Hammerschlag,y Samuel F. Dworkin,z Mikel G. Aickin,x

Scott D. Mist,{ Charles R. Elder,# and Richard E. Harris***Departments of Family and Community Medicine and Anthropology, University of Arizona, Tucson, Arizona.yOregon College of Oriental Medicine, Portland, Oregon.zDepartment of Oral Medicine, School of Dentistry, University of Washington, Seattle, Washington.xDepartment of Family and Community Medicine, University of Arizona, Tucson, Arizona.{School of Nursing and School of Medicine, Oregon Health and Science University, Portland, Oregon.#Kaiser Permanente Center for Health Research, Portland, Oregon.**School of Nursing and School of Medicine, University of Michigan, Chronic Pain and Fatigue Research Center, AnnArbor, Michigan.

Received2012.The projthors havAddress rFamily &E-mail: ri

1526-590

ª 2012 b

http://dx

Abstract: This dual-site study sought to identify the appropriate role for traditional Chinese med-

icine (TCM; acupuncture and herbs) in conjunction with a validated psychosocial self-care (SC) inter-

vention for treating chronic temporomandibular disorders (TMD)-associated pain. Participants with

Research Diagnostic Criteria for Temporomandibular Disorders–confirmed TMD (n = 168) entered

a stepped-care protocol that began with a basic TMD class. At weeks 2 and 10, patients receiving

SC whose worst facial pain was above predetermined levels were reallocated by minimization to

SC or TCMwith experienced practitioners. Characteristic facial pain (CFP: mean of worst pain, average

pain when having pain, and current pain; each visual analog scale [VAS] 0–10) was the primary out-

come. Social activity interference (VAS 0–10) was a secondary outcome. Patients were monitored for

safety. TCM provided significantly greater short-term (8-week) relief than SC (CFP reduction differ-

ence, �.60 [standard deviation of the estimate .26], P = .020) and greater reduction in interference

with social activities (�.81 [standard deviation of the estimate .33], P = .016). In 2 of 5 treatment tra-

jectory groups, more than two thirds of participants demonstrated clinically meaningful responses

($30% improvement) in pain interference over 16 weeks. This study provides evidence that TMD pa-

tients referred for TCM in a community-based model will receive safe treatment that is likely to pro-

vide some short-term pain relief and improved quality of life. Similar designs may also apply to

evaluations of other kinds of chronic pain. (ClinicalTrials.gov number NCT00856167).

Perspective: This short-term comparative effectiveness study of chronic facial pain suggests that

TCM is safe and frequently efficacious alone or subsequent to standard psychosocial interventions.

TCM is widely available throughout North America andmay provide clinicians and patients with a rea-

sonable addition or alternative to other forms of therapy.

ª 2012 by the American Pain Society

Key words: Facial pain, acupuncture, Chinese medicine, comparative effectiveness, temporomandibu-

lar disorders.

January 10, 2012; Revised July 22, 2012; Accepted August 4,

ect was supported by NIH/NCCAM grant U01AT002570. The au-e no conflicts of interest to declare.eprint requests to Cheryl Ritenbaugh, PhD,MPH, Department ofCommunity Medicine, 1450 N Cherry Ave, Tucson, AZ 85719.tenbau@email.arizona.edu

0/$36.00

y the American Pain Society

.doi.org/10.1016/j.jpain.2012.08.002

Temoromandibular disorders (TMD) includes a clus-ter of related conditions affecting the hard andsoft structures involved in movement of themandi-

ble. Chronic pain radiating from the temporomandibularjoint/masticatory muscles affects >10% of adults atany one time, and one third of adults will experienceTMD symptoms over their lifespan.50,53 TMD is commonlycharacterized by comorbidities, including headache,back pain, widespread pain, and fibromyalgia, andpsychosocial challenges including depression, anxiety,

1075

1076 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

and multiple nonspecific physical symptoms.7,19 Impair-ment in daily activities, excess reliance on healthcare,14,37,40,55 and dependence on narcotic analgesics11

are documented.Pain relief is the primary therapeutic treatment objec-

tive for patients and clinicians.15,25,33,52 Strategiesinclude various chronic pain medications, intraoralocclusal devices, physiotherapy, various surgeries, andarthroscopy. Psychosocial interventions have also beenevaluated, with some successes.21,16-18,22,28 Recentshort-term trials have assessed the effectiveness of phys-ically based treatments,6,30,41 with many TMD patientsseeking repeated courses of treatment over severalyears. Yet over a 5-year period, TMD signs and symptomsare, for a significant minority, not adequately ad-dressed.40 No overarching evidence-based rationale forselecting among TMD treatments has emerged.50 Thereis relatively frequent use of complementary and alterna-tive medicine (CAM) in conjunction with conventionalbiomedicine by TMD patients.13,42 Patients appear tobe seeking a more comprehensive and longer-lasting ap-proach to the management of their syndrome.Traditional Chinese medicine (TCM) views disease as

a constitutional imbalance and has the potential toprovide a whole system strategy for managing TMD.TCM encompasses acupuncture, herbal therapy, massage(Tuina), and breathing and relaxation exercises (Qigongand Tai Chi), yet acupuncture as monotherapy has beenthe predominant TCM-based clinical trial approach forTMD. The randomized controlled trial (RCT) literatureto date is encouraging for acupuncture treatment ofTMD.31 Of 4 reasonably high quality sham-controlledstudies, 3 reported significant acupuncture-relatedshort-term reduction in facial pain,47-49 while the fourthreported statistically significant pain reduction but nosignificant between-group difference.24 Three earlier tri-als had found acupuncture to be at least as effective asusual care (mainly occlusal splint therapy), but none ofthe 3 trials reported blinded treatment assessor(s).29,34,43

In our previous phase 2, randomizedpilot RCT, TCM (in-dividualized acupuncture and herbal therapy) providedshort-term reduction in TMDpain anddecrease indisabil-ity beyond that achieved by specialty dental care.45 TCMwasprovidedover a relatively short timeperiod—20visitsin 12 to 16 weeks. In the 3- to 6-month follow-up, gainsachieved during treatment declined, similar to otherTMD treatments. These results informed the present trialin which we shifted our focus from ‘‘cure’’ to ‘‘rehabilita-tion’’ management. The design was based on a real-world pain clinic within a comprehensive health plan.

Methods

Overview of Study Design and RationaleThis project was designed as a comparative effective-

ness (CER) study. According to the Institute of Medicinereport, comparative effectiveness research has 6 keyfeatures: Informing a specific clinical decision from thepatient perspective or a health policy decision from thepopulation perspective; comparing at least 2 alternativeinterventions, each with the potential to be ‘‘best

practice’’; describing results at the population and sub-group levels; measuring outcomes—both benefits andharms—that are important to patients; employingmethods and data sources appropriate for the decisionof interest; and conducted in settings that are similar tothose in which the intervention will be used in practice.27

Herewecompared the effectiveness ofwhole systemTCMto self-care (SC)management in amanner consistentwithan integrative TMD specialty clinic stepped-care strategy.This sequential allocation design is similar to an approachthat is being used in behavioral medicine/addiction re-search.32 The community-based TCM practitioners arefree to tailor treatment and, alongside the patients, toselect timingof the visits to reflect real-world clinical prac-tice. The pain and functional outcomes reflect those ofimportance to patients. The question we evaluated hereis whether there is a benefit to providing TCM treatment,either before or after a standard SC intervention.Participants who passed a phone screen were recruited,

consented, and began a 4-step eligibility process thatincluded (1) a baseline questionnaire; 2) the ResearchDiag-nostic Criteria for Temporomandibular Disorders (RDC-TMD) clinical examination by a project dentist (http://www.rdc-tmdinternational.org/TMDAssessmentDiagnosis/RDCTMD.aspx); 3)a standardizedTCMdiagnostic interviewby the project TCM diagnostician; and 4) a 2-hour educa-tional session, modeled on the educational session pro-vided within the Kaiser Permanente Northwest TMDclinic forall newTMDpatients. Thosepotential participantswhoremained interestedandeligibleafter theeducationalsession (thefinal step)wereentered into the studyandcon-tinued to the week 2 telephone interview data collection.Based on the week 2 data, those with worst facial pain(WFP) above a predetermined level (see below and Fig 1)were dynamically allocated by the statistician (M.G.A.) tothe psychosocial intervention (called here Self-Care or SCand described below) or whole system TCM45 for Period1. We have used S and T to denote these allocated groups.Thosewithpain below the cut-point automaticallywent toSC and are denoted as group s. Project managers notifiedparticipants of their treatment assignments and facilitatedthe scheduling of appropriate appointments. After datacollection in week 10, those who received SC (groups Sand s) who had substantial pain beyond a 2nd cut-pointwere againdynamically allocatedby the project statistician(M.G.A.) to TCM (now group ST or sT) or continued SC(groups SS or sS) for Period 2using the sameprocess. Partic-ipants who were automatically given SC in the first period(s) could continue in SC if they fell at or below the cut-point(group ss); theyare theonlygroupnot included in themainanalyses because there was not an allocation that wouldprovide a basis for comparison. All participants ever allo-cated to TCM treatment remained in that arm (group Tt).(These design elements can be visualized in Fig 1, describedbelow.) Final data collection for this report occurred inweek 18. Eight weeks was chosen as the interval betweenallocations to represent a reasonable trial period for SCand to evaluate an allocation flow representative of actualclinic practice. Here, the first allocation reflects sending pa-tientswith substantial pain toTCMearly. The secondalloca-tion reflects sending patients to TCM subsequent to

(s)WFP ≤ 7

(s)WFP ≤ 7

Assessed for eligibility n = 468 Not eligible n = 132 Not consented n = 92Did not complete run-in n = 76

39 allocated2 unable to notify

1 declined not allocation-related36 received TCM

36 followed up

Allocatedn = 168

88 continuing2 unable to notify

1 declined not treatment-related85 received SC

2 lost to follow-up83 followed up

36 continued TCM36 followed up

Legend

TCM solid Allocations

T = TCM

S = Self Care

Continuations (t) = TCM (s) = Self Care

Allocated tx square

Continuing tx oval

1 removedper protocol

40 allocated4 declined not allocated-related

36 received SC1 lost to follow-up

35 followed up

15 allocated1 refused allocation1 unable to notify

1 declined not allocation-related12 received SC12 followed up

6 continued1 declined not treatment-related

5 received SC5 followed up

14 allocated3 unable to notify11 received TCM

11 followed up

28 allocated1 refused study design

1 declined not allocation-related26 received TCM

26 followed up

27 continued1 removed per protocol1 refused assignment

1 unable to notify1 declined not treatment-related

23 received SC23 followed up

28 allocated2 refused allocation

26 received SC26 followed up

T T

S S

T

S

(t)

(s)

Week 2 Weeks 3–10 Weeks 11–18

SC dashed

Figure 1. The CONSORT diagram shows the progression of study participants through the first 2 allocation periods of the study, theshort-term component reported here. It illustrates the study design andWFP cut-points and provides the number of participants pro-vidingoutcomedata, beginningwith thefirst allocation. In each group, the number of participants beginning the intervention in thatphase is shown as the top number, and the number of evaluable participants at the end of that phase is shown in the bottom number.Details of the reasons for participant losses in each group are shown. Details for the losses in the recruitment process are provided inthe text.

Ritenbaugh et al The Journal of Pain 1077

1078 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

a reasonable trial of usual care, as represented by the SC in-tervention. The design anticipated minimal heterogeneitybetween these 2 allocations. The study permitted up to 20TCM visits distributed, at practitioner and participant dis-cretion, over a period of up to 1 year. Here we report theshort-term 2-period treatment evaluation. The longer-term observational study will be reported elsewhere.

Study Setting and RecruitmentThe study took place in Tucson, Arizona, and Portland,

Oregon. Screening for TMD, TCM diagnosis, TCM treat-ment, and SC intervention activities were all based incommunity practice settings. Participants at both siteswere recruited through newspaper advertisements andemail list-serves of various types. In Tucson, there wasalso an active community outreach component to en-hance the recruitment of minorities. At both sites, theresponse to newspaper advertisements was strong, re-flecting a high interest in CAM as well as the relativelack of insurance coverage for TMD (considered a dentalcondition) and for CAM. Individuals responding to out-reach in either city contacted our call center in Tucson us-ing a toll-free number. The call center staff had all theinformation available for both sites and provided allscreening and scheduling to all participants. Potentialparticipants completed an initial phone screen askingabout TMD symptoms. Those who were ages 18 to 70and reportedWFP at 5 or abovewere eligible to continueto the in-person local screening and consenting inter-view. At the screening interview, participants consentedfor the study and completed the baseline questionnaire.They were sent for the clinical RDC-TMD examination bya study dentist and for a TCM diagnostic interview bya study TCM evaluation practitioner.

Participant EligibilityInclusion criteria were age 18 to 70, WFP $5, research

diagnosis of TMD,36 presence of 1 of 10 TCM diagnoses(chosen to account for 90% of participants in priorstudy45), and completion of the run-in (TMD class) pro-cess. Exclusion criteria, evaluated at the consent interviewor RDC-TMD clinical evaluation, included 1) serious pa-thology of the temporomandibular joint, eg, infection,rheumatoidarthritis, fracture; presenceof cancer or acuteinfection of the teeth, ears, eyes, nose, or throat; andindividuals undergoing active orthodontic treatment; 2)serious psychiatric conditions; 3) surgical implants fortreatment of TMD; 4) bleeding disorders; 5) other life-threatening conditions, eg, cancer, uncontrolled severehypertension; 6) severe joint/disk displacement; 7) use offull dentures; 8) use of medications for which study herbsare contraindicated; and 9) current pregnancy or plans tobecome pregnant during active treatment. Women werequeried about pregnancy at every assessment point dur-ing the study and at every TCM visit. (This is usual practicein TCM as pattern differentiations, altered in pregnancy,might necessitate use of acupuncture points and/or herbsnot included in the study protocol.)All participants who met the RDC-TMD case-definition

criteria and had an eligible TCMdiagnosis participated in

a 2-hour class at the local study site. The class, developedfor this project by S.F.D., covered the nature of TMD, itspatterns of progression/nonprogression, precipitatingand relieving factors, and suggestions to help with jawrelaxation. If still interested, participants were movedto enrolled status, which led to the week 2 data collec-tion.Study dentists were trained and calibrated to meet re-

search criteria by one of the investigators (S.F.D.) andwere recalibrated midway through the study. StudyTCM diagnosticians along with the study TCM practi-tioners were calibrated in TCM diagnoses by another in-vestigator (S.D.M.)39 and recalibrated midway throughthe study as described below in greater detail. TheRDC-TMD dentists and TCM diagnosticians, 1 each percity, remained with the study throughout its duration.

TCM Intervention ProtocolThe protocol, designed to provide the best individual-

ized TCM care within the confines of a research study,could include acupuncture, moxibustion, Chinese herbs,massage (Tuina), and lifestyle and nutrition counseling.Participants had a total of 20 acupuncture visits and 20weeks of herbs available within a 1-year period fromthe first treatment visit. The TCM practitioner and theparticipant were encouraged to schedule 6 to 10 visitsin the initial 8-week period and to partition the remain-der of visits in an individually appropriate manner. AsTMD has a recurrent nature, this schedule was intendedto permit treatment of flare-ups when they occurred.The initial TCM diagnostic interview by the treatingTCM practitioner followed the same protocol as thatused in the screening TCM diagnostic interview men-tioned above and fully described in Mist et al.39 Theprocess included a detailed history, assessment of wristpulses, examination of the tongue, and concluding diag-nosis, with data collected on standard forms. Thisdiagnosis, which benefited from interpractitioner cali-bration,39 guided the selection of acupuncture points,herbal formulas, and lifestyle recommendations.Acupuncture treatments included a core set of points

congruent with those identified in the meta-analysis offacial pain treatment with acupuncture,46 supplementedby diagnosis-specific points as well as points, whereneeded, for headaches, insomnia, stomach upset, or de-pression (see Table 1). The total number of needles perparticipant visit was limited to 20.Theherbalprotocolwasdevelopedasan investigational

new drug (IND) application to the Food and Drug Admin-istration (FDA). For each of 12 TCMdiagnoses, base herbalformulas were specified. Each formula was modifiablewith any of the 65 herbs that composed the formulary(within recommended ranges), and practitioners hadguidelines of traditional ranges of herbs comprisingeach formula as outlined in standard texts.9,12 As part ofthe protocol per the FDA and the National Center forComplementary and Alternative Medicine (NCCAM),practitioners documented the exact formulationprepared on each occasion, and participants were askedto keep a log of their herbal ingestion.

Table 1. Herb and Acupuncture Protocols for 2 Most Frequent TCM Differentiations: Examples Arefor Participants Presenting Similar Symptoms, Including Insomnia and Headache

Base acupuncture points ST7 and/or ST6, GB20 and/or GB21, taiyang, LI4, LV3

Liver Qi Constraint

Additional points for diagnosis GB41, GB40, GB34, LV14, LV13

Base herbal formula Xiao yao san or Chai hu shu gan tang

Adjustments to formula Increase dose of bai zhu and fu ling, add suan zao ren [Increase Rhizoma Atractylodis

Macrocephalae and Poria, add Semen Zizyphi Spinosae]

Qi and Blood Stagnation

Additional points for diagnosis Local and distal Ah Shi

Base herbal formula Tong qiao huo xue tang

Adjustments to formula Add dan shen and shi chang pu [add Radix Salviae Miltiorrhizae and Radix Rehmanniae preparata]

Ritenbaugh et al The Journal of Pain 1079

Accordingly, the FDA aspects of the protocol were fo-cused exclusively on safety. All herbs, supplied in 5:1granule form, were purchased from Mayway Corpora-tion (Oakland, CA). They were GoodManufacturing Pro-cess (GMP) and Australian Therapeutic Goods (ATG)certified, which included testing for heavy metals andmicrobial content. Granules were prepared by sprayingdried herbal concentrates onto either maltose or micro-crystalline cellulose, a nonallergenic carrier, to forma fine powder. Samples were retained from each lot forpotential examination in the case of problems arising.Per FDA requirements for IND approval of the herbs,participants had laboratory tests for liver function (as-partate transaminase, alananine transaminase, total bil-irubin), renal function (creatinine, blood urea nitrogen),coagulation (International Normalized Ratio), bloodcount (abbreviated blood count), and urinalysis per-formed at the time of assignment to the TCM protocoland at 6 weeks and 1 year following start of TCM. Studymedical directors at each site reviewed all laboratorytests with any out-of-range values and provided guid-ance to the principal investigator (C.R.) and participants,when any remediation or treatment was necessary.Table 1 demonstrates the flexibility of the protocol by

showing the interventions for an example participantwith either Liver Qi Constraint or Qi and Blood Stagna-tion due to injury, and experiencing both insomnia andheadache.

TCM Practitioner Qualifications andTrainingThe 8 TCM practitioners who provided treatments (4 in

each community) had a minimum of 5 years’ experiencewith acupuncture and herbs. The 2 diagnosing practi-tioners each had more than 10 years’ experience andwere faculty members at collaborating traditional Chi-nese medicine schools. Three practitioners were trainedin China, and the rest had training from accredited Mas-ter’s level programs in the US. In order to increase thelikelihood that similar diagnoses were made and there-fore similar treatments were provided, the TCM practi-tioners from both sites met in Tucson in project year 1to review the protocol andmake consensus adjustments,and to practice diagnosing and giving per protocoltreatments.39 The protocol was originally developed bya consensus process among faculty at theOregon Collegeof Oriental Medicine in Portland as part of the prior

study. Practitioners met in person or by conference callevery 3 months with S.D.M. to review the protocol anddiscuss any unusual circumstances that were encoun-tered. Practitioners were not aware of the specifics ofthe study design, nor were they aware of any details ofparticipant assessments prior to beginning treatments.Participants were assigned to practitioners to maximizeconvenience for participants and to achieve balanceddistributions of caseloads over time. Because of the geo-graphic distributions of participants and practitioners,both goals were achieved. Assignment was not basedon any other participant characteristics.

SC Intervention Protocol

TMD Introductory Class

The intervention for all participants began with a 2-hour SC class; completing the class was considered partof the run-in phase. The inclusion of this initial educa-tional component (SC class) for all participants was basedonourprior studyfinding thatmanyTMDpatientsdidnotunderstand that their conditionwas chronic and nonpro-gressive andwere anxious about their long-term progno-sis. The class, based on an existing TMD class, providedbasic information on TMD and provided a few SC strate-gies aimed toward relaxation of the mandibular muscles.

SC Interventions

The 2 SC interventions were designed to match theTCM interventions in time and attention during the spec-ified study intervals. The time and attention matching inthe first two 8-week periods was based on the followingassumptions: 1) there would be a TCM intake (1 hour)and 7 TCM treatment sessions at .5 hours each (3.5 hours)in the first 8 weeks for a total of 4.5 hours; and 2) therewould be 2 in-person SC education/training sessions(1.5 hours each) and 3 phone call follow-ups (.5 hourseach) in each SC arm for a total of 4.5 hours.

Period 1

The Period 1 SC protocol developed for this study wasmodified from the tailored SC intervention cited earlier16

by S.F.D. and associates, who oversaw all aspects of PhaseI SC, described below, including manual development,training, and quality assurance on the intervention.(The manuals are available from S.F.D.) The Period 1 SCprotocol was oriented primarily to TMD patients who,

1080 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

independent of pain level, were not psychosociallydisabled. SC included the following elements: 1) educa-tion about the biopsychosocial model of TMD, chronicpain, the multifaceted aspects of TMD etiology, manage-ment methods, and the rationale for self-management;2) guided reading with structured feedback, usingparticipant-completed forms to explore the participant’sunderstanding of and identification with major themes,such as the rationale for breathing and relaxationmethods, TMD knowledge, communicating with healthcare providers, emotions, and bodily changes; 3) relaxa-tion and stress management training, including trainingin abdominal breathing, general muscle relaxationmethods, and relaxation of head, neck, and masticatorymuscles (the 2-hour class in the run-in period briefly cov-ered the role of stress and negative psychological statesas potential factors in exacerbating or maintaining pain-ful TMD symptoms, including methods for detecting andmanaging stress); 4) self-monitoring of signs and symp-toms, enabling participants to detect changes in theirphysical status in order to reinforce positive SC behaviorsand to call attention to negative factors that might bemodified through SC methods (eg, detecting effects ofparafunctional oral behaviors); 5) development of a ‘‘Per-sonal TMD Self-Care Plan,’’ a central component of the SCintervention, which allows the participant, with guid-ance and assistance from the interventionist, to developa regular schedule of individually tailored coping behav-iors to correct or ameliorate specific physical, psycholog-ical, or emotional factors that could exacerbate ormaintain TMD symptoms (eg, specifying times when re-laxation, jaw stretching exercises, ormonitoring of symp-toms would be performed); 6) supervised practice andreinforcement of prescribed SC treatments, eg, observ-ing participant performance of prescribed exercises dur-ing regularly scheduled SC sessions and providingfeedback and positive support, using follow-up tele-phone contacts to elicit changes in symptomatologyand compliance with regimens prescribed; and 7) main-tenance and relapse prevention, to foster recognitionof obstacles to maintaining the Personal TMD Self-CarePlan and to introduce self-initiated corrective behaviorsto overcome or reduce such obstacles.Two manuals were developed for and used in SC. The

interventionists’ manual, which standardized conductduring sessions and intervening telephone contacts, in-cluded scripted materials, readings and reading feed-back forms, exercises, symptom monitoring forms, andpersonal care plans. ‘‘A Patient’s Guide to Self Care forTMD,’’ given to each participant, contained TMD educa-tion and reading materials as well as blank forms.

Period 2

The second SC component was based on a widely usedresiliency intervention44 and was adapted for thisproject with the assistance of one of its developers(Dr. Andrew Shatte) and an integrative pain physician(Dr. Heather Tick). Resiliency is a lay-language laypersonintervention grounded in cognitive behavioral therapythat has been shown to be useful in treating TMD. Theintervention was delivered in the same time frame as in

Period 1 (2 in-person sessions, 3 phone calls). A patientself-help manual supported the intervention with moni-toring guides and tips, and brief homework and self-assessment exercises. The in-person sessions focused on2 key points: 1) the relationship of thoughts to feelings,and how to change thought patterns; and 2) the role ofthinking traps and how to overcome them. In-person ses-sions focused on understanding basic concepts, workingthrough scenarios developed from Dr. Tick’s experiencewith chronic pain patients, and identifying situations tolook at in the coming weeks. Follow-up phone calls pro-vided check-ins on the real-world implementation of thelessons and use of self-help materials.Per the design, participants could be assigned to SC be-

cause theywere below the pain cut-point or could be allo-cated by minimization if they were above the cut-point.However, practitionerswerenot informedof theseaspectsof the design, nor of the source of individual assignmentsto SC. There was only 1 SC interventionist at each location(Tucson, Portland), andall participants at that site receivedintervention from the local interventionist.

SC Interventionist Qualifications andTrainingThe SC interventionists were a retired dentist (Port-

land) and an experienced health behaviorist who hadworked onmanualized interventions in other behavioralclinical trials (Tucson). Both components of the interven-tion had manuals for the interventionists. For theTMD SC intervention, the interventionists received 8hours of instruction. Topics included TMD etiology,pathophysiology, and clinical management, delivery ofeducational materials, behavioral skills training, andcharting. Quality assurance was implemented via quar-terly phone conferences, and the trainer was readilyavailable by phone for questions. In addition, therewas an in-person review with the interventionists atthe end of the first year. For the resiliency componentin Period 2, interventionists received 8 hours of training,with follow-up phone conference debriefings after thefirst few participants and quarterly thereafter. Interven-tionists tape-recorded randomly chosen sessions forquality control and feedback in both types of sessions.

Study Approvals and SafetyTheHuman Subjects Protection Programs (institutional

review boards [IRBs]) at the University of Arizona and theOregon College ofOrientalMedicine approved all proce-dures affecting participants. The NCCAM Office of Clini-cal and Regulatory Affairs approved the overall protocol.The herbal protocol operated under an IND statusthrough the FDA. The study was run under the guidanceof an independent 5-member Data and Safety Monitor-ing Board, which met twice yearly and reported its delib-erations and findings to the study team, NCCAM, and theIRBs, and a Steering Committee that met monthly, whichincluded the NCCAM Project Officer, an external advisor,the key study investigators, and project managers.IRB- and Data and Safety Monitoring Board [DSMB]-

approved protocols for reporting and adjudicating

Table 2a. Demographic Characteristics ofParticipants Allocated at Weeks 2 and 10*

1ST ALLOCATION

(WEEK 2)2ND ALLOCATION

(WEEK 10)

SC TCM SC TCM

Numbery 40 39 43 42

Age, years

[mean (SD)]

42.3 (13.5) 42.9 (13.0) 43.7 (12.4) 43.6 (12.0)

PERCENT

Gender

Female 85.0 87.2 86.0 88.1

Ethnic categories

Hispanic or Latino 10.0 10.3 11.6 11.9

Not Hispanic or Latino 85.0 84.6 88.4 83.3

Unknown (individuals not reporting

ethnicity)

5.0 5.2 0 4.8

Racial categories

White 82.5 84.6 86.0 83.3

Nonwhite 5.0 7.7 7.0 4.8

Unknown or not reported 12.5 7.7 7.0 11.9

Education

#High school 12.5 7.7 14.0 21.3

Some college 37.5 38.5 23.8 31.0

College graduate 25.0 28.2 28.6 19.1

Postgraduate education 25.0 25.6 33.3 28.6

Marital status

Married/partnered 37.5 59.0 46.5 54.8

Divorced/widowed/separated 27.5 10.2 30.2 21.4

Never married/partnered 35.0 30.8 23.3 23.8

Not known 0 0 0 0

Income ($)

No response 5.0 2.6 11.6 4.8

<25K 32.5 30.8 23.3 33.3

25–50K 22.5 35.9 27.9 31.0

50–100K 27.5 25.6 25.6 21.4

>100K 12.5 5.1 11.6 9.5

TCM differentiations (most salient)

Liver Qi Constraint 47.5 53.8 34.9 47.6

Qi and Blood Stagnation 37.5 38.5 51.2 38.1

Otherz 15.0 7.7 13.9 14.3

*None of the between-group differences within allocation periods are signifi-

cant at P < .05.

yNote that per design some of the same people are represented in the baselines

for SC in Period 1, and SC and TCM in Period 2.

zFull details of other baseline differentiations are found in Mist et al.39

Ritenbaugh et al The Journal of Pain 1081

adverse events were in place at both study sites. Studymedical directors were responsible for reviewing all ad-verse events and recommending action to the principalinvestigator (C.R.). To ensure participant safety in rela-tion to potential mental health problems, all staff mem-bers were trained in the implementation of a mentalhealth protocol to ensure that any participants appar-ently manifesting mental health or emotional problemshad appropriate resources available.

Outcome Measures and Data CollectionProceduresData for the short-term analyses presented here were

collected at baseline (study consent) and at weeks 2 (priorto first allocation), 10, and 18. Additional data collection

points are part of the long-term follow-up reportedelsewhere. The baseline questionnaire was a paper-based form with the entire RDC-TMD Axis II item set, aswell as other outcome measures repeated at every subse-quentmeasurement point. A single trained interviewer atthe Tucson call center used a computer-assisted telephoneinterview (CATI) system to collect all of the short-term fol-low-up data at weeks 2, 10, and 18, the data used for theoutcome analyses presented here. Calls were recorded forrandom quality assurance checks. The interviewer waskept unaware of study design details and blinded to indi-vidual participant treatment assignment. Participantswere encouraged not to divulge any treatment-relatedinformation to the interviewer, and the interviewer wastrained to avoid any such discussions. The site-specificproject manager was responsible for all necessarytreatment-related conversations such as appointmentand phlebotomy scheduling. A tracking system in Tucsonpermitted close monitoring of participant status at bothsites in relation to all aspects of the study. Specific studystaff had their access restricted to only the informationthat was needed for their roles, and they could not viewother participant-related information. This permittedoverall study management while maintaining blinding.We chose the CATI system for primary data collection

in the short-term study phase because of previous diffi-culty in obtaining timely and complete data in a similarstudy population in which we were relying on partici-pants to fill out and return paper-based self-reports. Atthe study consent visit, participants were shown thedata collection form for the telephone interviews sothat they could be confident that the contacts wouldbe brief. These study phone contacts took 10 minuteson average. The telephone interviews included the studyoutcomes described below.The primary study outcome was characteristic facial

pain (CFP), the average of WFP, average pain when hav-ing pain, and facial pain now, based on the RDC-TMD.The study design group assignment criteria (see Fig 1)were based on WFP, because this was the measure thatwas available from the previous study to guide this de-sign45; because of its role in the study we considered itas a second primary outcome. The main secondary out-come was pain interference with social activities. OtherRDC-TMD measures, also collected at study baseline,are shown in Table 2b. The tertiary outcomes also col-lected in the more abbreviated telephone follow-upsare listed in Table 4. In addition to the 7 pain itemsfrom the RDC-TMD, these included a 1-item summarysleep measure (how often do you awaken fresh and res-ted?), a brief depression measure (PHQ2),23 the PatientEnablement Instrument (PEI),26 and the Arizona Integra-tive Outcomes Scale (AIOS), an overall measure of well-being.8,38 In addition, at each follow-up each participantprovided a complete listing of pain-related medicationsused in the previous month, including dosage and fre-quency,20 from which we derived the measure ‘‘numberof medications’’ shown in this table.Symptoms were monitored in detail at each interven-

tion visit, under DSMB guidance, to identify possibleharms. The same form was used in both the SC and

Table 2b. Baseline Pain Characteristics* forParticipants Allocated at Weeks 2 and 10

1ST ALLOCATION (WEEK 2) 2ND ALLOCATION (WEEK 10)

SC TCM SC TCM

Number 40 39 43 42

VARIABLE MEAN (SD)

Worst facial pain [0–10] 8.1 (1.4) 8.1 (1.2) 7.5 (1.5) 7.6 (1.5)

Average facial pain [0–10] 6.0 (1.6) 6.5 (1.8) 5.8 (1.7) 5.6 (2.2)

Facial pain today [0–10] 5.0 (2.0) 5.3 (2.2) 4.5 (2.2) 4.5 (2.3)

Characteristic facial pain

[0–10] (mean of 3 above)

6.4 (1.4) 6.6 (1.4) 5.9 (1.5) 5.8 (2.0)

Days of facial painy 4.9 (1.4) 4.8 (1.3) 4.7 (1.4) 4.6 (1.6)

Amt. interferes with daily

activities [0–10]

4.3 (2.3) 3.8 (2.6) 3.5 (2.2) 3.8 (2.7)

Amt. interferes with social

activities [0–10]

3.8 (2.5) 3.3 (2.8) 3.0 (2.1) 3.3 (2.7)

Amt. interferes with ability

to work [0–10]

3.8 (2.4) 3.8 (2.8) 3.0 (2.3) 2.9 (2.7)

Depression [1–4] 2.0 (.8) 1.8 (.6) 1.7 (.6) 1.8 (.8)

Sleep [1–4] 2.8 (.8) 2.5 (.8) 2.7 (.8) 2.6 (.8)

N of medications 2.2 (1.5) 1.8 (1.5) 1.8 (1.4) 1.9 (1.6)

AIOS [0–10] 5.5 (2.1) 5.6 (2.0) 5.6 (1.9) 5.9 (1.9)

PERCENT

Duration of pain

<1 year 10.0 10.3 7.0 4.8

1–10 years 55.0 43.6 41.8 59.5

>10 years 35.0 46.1 51.2 35.7

Visited a practitioner for

pain treatment

No 5.3 18.4 16.3 4.9

Yes 94.7 81.6 85.7 95.1

Nature of facial pain

Continuous 47.5 41.0 44.2 43.9

Intermittent 52.5 58.9 55.8 56.1

Graded Chronic Pain score

0–2 30 35.9 37.2 42.8

3–4 70 64.1 62.8 57.1

TMD Diagnostic Groups

(RDC-TMD Axis I)

Group 1a 53 39 61 46

1b 41 42 25 41

Any Group 2 20 15 33 21

Group 3a 63 67 47 52

3b-c 5 0 5 2

Group 1 1 3a 63 62 44 48

*Note that these do not match Fig 2; these are baseline values, whereas Fig 2

shows the values at the time of allocation by minimization.

y1 = 0–3 days; 2 = 4–7 days; 3 = 8–14 days; 4 = 15–21 days; 5 = 22–27 days;

6 = every day (out of the past month).

Table 3. Number of Visits* by Trajectory in TimePeriods 1 and 2

PERIOD AND TRAJECTORY

MEAN N OF

VISITS (SD)APPROXIMATE

TIME (HRS)N OF

PARTICIPANTS

Period 1

Assigned to SC

(pain below threshold) (s)

3.9 (1.4) 4.0 88

Allocated to SC (S) 3.3 (1.8) 3.7 40

Allocated to TCM (T)y 6.4 (3.1) 4.2 39

Period 2

Continuing SC

(ss or Ss)

3.8 (1.8) 3.9 27

Allocated to SC

(sS or SS)

3.9 (1.7) 4.0 42

Allocated to TCM

(sT or ST)y6.1 (2.9) 4.1 42

Continuing TCM (Tt) 4.7 (1.9) 2.4 36

*Time and attentionmatchingwas designed on time, not visit number. In-person

SC sessions were 1.5 hours (2 per unit), phone calls were .5 hours (3 per unit),

initial TCM visits were 1.5 hours, and follow-up sessions were .5 hours (6 per

unit).

yNumber of visits was significantly greater in the TCM intervention.

1082 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

TCM arms. It included a checklist of 24 common symp-toms, including those that might be caused by herbs,acupuncture, lifestyle changes, or use of any recommen-ded SC strategies. For each symptom, the participantchecked whether or not it had occurred since the lastassessment. If so, the participant indicated 1) whetherit was new; 2) severity—mild, moderate, severe; 3)whether it was related to treatment; and 4) the changesince previous assessment—worse, none, better. Practi-tioners and interventionists had protocols for respond-

ing to any severe or worsening symptoms (adverseevents). Extensive evaluations were undertaken on thesedata at each semiannual DSMB meeting to look for pat-terns by type of intervention. In addition, participantswere asked at each intervention visit and at eachfollow-up data collection telephone interview whetherthey had used the emergency room or been admittedto the hospital since the last follow-up. Every affirmativeanswer was considered an adverse event, and follow-updata collection was initiated per DSMB-approved proto-col. Severity and relationship to treatment assessmentfollowed standard National Institutes of Health defini-tions; all final decisions regarding severity and relation-ship to treatment were made by consensus of the 2medical directors (Tucson and Portland) with concur-rence of the principal investigator (C.R.). Each adverseevent was reviewed by the DSMB. The study includeda protocol for addressing mental health events, and allstaff members and practitioners were trained in its use.

Statistical ApproachDynamic allocations to treatment groups at weeks 2

and 10 were accomplished by an automated design-adaptive allocation procedure1-5,51 that sequentiallybalanced the SC and TCM groups with regard to WFP,gender, depression, and age as each person becameeligible for allocation. This was done becausesimulation studies have shown that conventionalrandomization in small studies is unacceptablyinefficient, both at producing balanced treatmentgroups and at accurate effect estimation.5,51 Balancingfactors were used for adjustment in the primaryanalysis, again following the results of Aickin5 andTaves,51 in accordance with the CONSORT statement, inwhich ‘‘minimization’’ is regarded as equivalent to ran-domization. Allocations were computer-generated byDr. Aickin using a computer program to which he alonehad access, thereby concealing the allocation process

Table 4. Main Outcomes: Results of Per Protocol Analysis of Overall Short-Term Effects ComparingTCM With SC

OUTCOME [POSSIBLE RANGE OF VALUES] BASELINE AVERAGE (WEEK 2)* TOTAL TCM EFFECT IN COMPARISON TO SCy (SDE) [P VALUE]

Primary outcomes

Characteristic facial pain [0–10] 6.5 �.60 (.26) [.020]

Worst Facial pain [0–10] 8.5 �.58 (.29) [.045]

Secondary outcome

Interfered with social activities [0–10] 3.3 �.81 (.33) [.016]

Tertiary outcomes

Average facial pain [0–10] 6.3 �.62 (.27) [.023]

Facial pain now [0–10] 4.8 �.49 (.33) [.144]

Days of facial painz [0–6] 5.0 (22–27 days) �.05 (.27) [.841]

Interfered with daily activities [0–10] 4.3 �.60 (.32) [.070]

Depression [1–4] 2.0 �.11 (.09) [.248]

Sleepx [1–4] 2.6 �.26 (.11) [.020]

N of medications 1.7 �.08 (.13) [.543]

Patient enablement [1–4] 2.4 .27 (.09) [.005]

AIOS (overall well-being) [0–10] 5.9 .58 (.25) [.022]

*Participants allocated to SC or TCM at week 2 or 10.

yThe effect represents the difference between the change scores (TCM � SC), shown in the units associated with each outcome measure.

z1 = 0–3 days, 2 = 4–7 days, 3 = 8–14 days, 4 = 15–21 days, 5 = 22–27 days, 6 = every day (out of the past month).

xReverse coded: lower is better.

Ritenbaugh et al The Journal of Pain 1083

from all other project staff. Moreover, participants wereallocated in blocks, and an undisclosed feature of the al-location program rendered accurate prediction of alloca-tion extremely unlikely. Allocations were provided to theproject managers after data collection and at the timewhen participants needed to be informed. Staff playedno role in generating allocations nor had any potentialto manage or affect the process.The analysis of the first 2 dynamic allocations pre-

sented here was undertaken on an intent-to-treat ba-sis. Missing data were rare and were not replaced byimputation. The primary outcome analysis was basedentirely on study telephone-administered question-naires, which were taken to represent the times atwhich they were intended to be administered in thestudy (weeks 2, 10, and 18 for the short-term phase).Thus, variations that occurred in the exact timing ofstudy questionnaires were not incorporated into theanalysis, because they were driven by the practicalitiesof participant choice of treatment timing and by studyconstraints.The short-term analysis presented here, carried out as

specified in the study design, used outcomes from 2phases, week 2 to week 10, and week 10 to week 18.For each period, the outcome was expressed as a changescore (value end of period minus value start of period).The regression analysis used the change score as the out-come, and explanatory factors were TCM group indica-tor, age, male indicator, depression, baseline valueat week 2, and WFP at week 2 (each centered at itsmean). A random effects model took into account thatsome participants appeared in both time periods (thecluster option of the regress procedure in Stata, v.9.1[StataCorp LP, College Station, TX]). The coefficient ofthe TCM indicator was the primary effect, for which 2-sided P values were computed. This coefficient reflectsthe additional improvement due to TCM (above thechange due to SC) on the relevant scale for each item.

Age, WFP, gender, and depression were included basedon the findings of Aickin5 and Taves.51 Table 4 presentsresults for all outcome measures that were available forevaluating the short-term impact of the interventions.Note that participants assigned to the SC conditionwith pain levels below the relevant thresholds do notcontribute to the analyses for that period.To provide some indication of the clinical meaningful-

ness of the overall intervention trajectories, the percentachieving greater than 30% improvement was calcu-lated per trajectory simply by counting those participantswhose week 18 value was at least 30% lower than theirweek 2 value.

Power ConsiderationsBoth the study design and the sample size determina-

tion were based on the pain trajectories of participantsin the pilot study. At power 85% and significance 5%,the detectable effect on the primary outcome of WFPchange was 1 unit (on the 0–10 scale), determined byapplying the current analysis to the pilot data, and fac-toring up to a sample size of 150. From the results re-ported below, the actual detectable effect was .8 units.

ResultsThe flow of participants into and through the short-

term phase of the study is summarized in detail in theCONSORT diagram (Fig 1). Briefly, 468 potential partici-pants were screened, 336 were eligible for referral toconsent, and 244 consented between September 2006and December 2007. The main reason for lack of consentwas study burden. One hundred sixty-eight entered intothe study, almost 30%of those initially expressing any in-terest. The main reasons for not completing run-in wererealization of study burden, individuals too busy to com-plete all study activities, study delays, and inability tocontact participants for study activities. The recruitment

1084 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

target of 80 participants per site was exceeded slightly atboth sites. Over the 2 allocation periods, 2 participantswerewithdrawnper protocol formedical reasons (1 priorto initial allocations, 1 in second SC continuation group).Of 81 total participants allocated to TCM, we were un-able to notify 5, 2 withdrew not related to treatment al-location (illness in family, surgery, etc), and 1 declinedbecause of the blood work requirement. The remaining73 participants all received treatment and providedfollow-up data. Over the 2 allocation periods, therewere 204 opportunities for participants to be offeredSC. Of those, we were unable to notify 4, 8 declined forreasons not related to the treatment group, and 4 re-fused the assignment and withdrew from the study.One hundred eighty-seven received treatment, withfollow-up on 184.The study design and flow of participants through the

study between weeks 2 and 18 is also shown in Fig 1. Atthe first allocation point, 88 were at or below the WFPcut-point (predefined as WFP = 7) and assigned to SC (in-dicated as [s]), whereas 79 whowere above the cut-pointwere dynamically allocated between SC (S) and TCM (T).In the second period, all first period TCM participantscontinued with TCM (Tt). Of the remaining participants,85 continued to have pain above the second cut-point(predefined as WFP = 5); 42 were allocated to TCM (STor sT) and 43 to SC (SS or sS) at the second allocation.Thirty-three participants were at or below the cut-pointand continued on SC (27 ss, 6 Ss) and did not contributeto further analyses.Baseline values for demographic, TCM, and TMD

characteristics are shown in Tables 2a and 2b for all par-ticipants entering each allocation group in each time pe-riod. With regard to RDC-TMD Axis I physical diagnoses,analyses revealed a distribution of Axis I diagnoses inagreement with numerous other studies. The Axis II clas-sifications were also similar to replicated well-publishedfindings that TMD patients do report appreciableamounts of depression, somatization, and persistentpain of longduration. However, the proportion of partic-ipants in Graded Chronic Pain levels 3 1 4 was higherthan anticipated from the previous study. Note that thestarting pain level values tend to be higher in the partic-ipants allocated at week 2 compared to week 10. This isto be expected, as those with lower pain at baselinewere more likely to be assigned to SC at week 2 andnot be allocated until week 10. Full details of baselineTCM diagnoses are provided elsewhere.39

Table 3 shows the number of visits participants hadin each trajectory in each period. In both TCM andSC, participants completed fewer visits than providedfor in the protocol in both time periods, and in gen-eral, participants completed fewer treatments in thesecond period than in the first. However, because ofthe different durations of visits, time spent per periodby participants in TCM and SC visits continued to besimilar.The results of the primary short-term analyses as pre-

specified are shown in Fig 2 and Table 4. Fig 2 shows theamount of change for each group under each treat-ment condition for CFP and WFP (primary outcomes);

sample sizes in each subgroup are shown in Fig 1. Par-ticipants improved during each treatment phase innearly every treatment condition. Table 4 shows theoverall short-term (8-week) effects of TCM in compari-son to SC combined over the 2 treatment periods for al-located participants on all of the evaluated outcomevariables. There were statistically significant additionalbenefits from TCM over SC with regard to our primaryoutcomes, CFP and WFP (�.60, P = .020 and �.58, P =.045, respectively). In addition, our prespecified second-ary outcome, ‘‘interference with social activities,’’showed greater improvement in TCM (�.81, P = .016).Statistically significant greater improvements werealso seen for TCM in the overall measures of well-being (AIOS) (.58, P = .019), sleep (.27, P = .020, 1–4scale), and Patient Enablement (.27, P = .005). Therewere no measurable differential benefits from TCM indepression or the number of medications being taken.Thirteen participants were taking opioids at the startof the study. Detailed evaluation of medication use pat-terns found no individuals who stopped their opioidmedication use during these time periods. Additionalsecondary analyses evaluated whether TCM differentia-tion (Liver Qi Constraint, Qi and Blood Stagnation, orOther) at baseline or duration of TMD prior to thestudy, was related to outcome effects of TCM. Neitherhad a significant effect on any outcome (data notshown). Within the interventions, there was a trend to-ward a significant impact of number of visits on painimprovement in TCM but not SC.To provide a clinically related interpretation of these

results, we estimated the percent of participants achiev-ing the minimum clinically important difference over 16weeks in each trajectory, applying the commonly used30% criterion. In summarizing the results of Table 4 bytrajectory, Fig 3 presents the percent of participantsachieving, over 16 weeks, at least 30% reduction in ourmain outcome variables—CFP, WFP, and interferencewith social activities. Individuals are grouped by alloca-tion trajectories as shown in Figs 1 and 2; sample sizesper trajectory are provided in Fig 1. In 2 of the 5 trajecto-ries, more than two thirds of the participants achievedgreater than 30% improvement in social interference.Both of these trajectories included TCM.Statistical and graphical analysis of negative side

effects, monitored in both interventions at each treat-ment visit as described above, revealed neither clinicallymeaningful nor statistically significant differencesbetween interventions except for occasional and mildgastrointestinal disturbances associated with herbal for-mulae, which were immediately addressed by the TCMpractitioners, or rare mild bruising from acupuncture.The only clinically significant adverse event attributableto an intervention was a mild adverse event—ear celluli-tis—attributable to ear acupuncture in a single personwho had intermittent ear cellulitis prior to study entry.After this event, the protocol was amended so that allparticipants were queried about previous cellulitis; ifthe condition was reported, acupuncture was to beavoided in that area. In fact, none was subsequently re-ported. No hospitalizations or emergency room visits

Week 2 Weeks 3-10 Weeks 11-18

CFP: 6.5 => 5.1WFP: 8.5 => 6.9

CFP: 6.6 => 5.5WFP: 8.6 => 7.3

CFP: 5.1 => 4.9WFP: 6.9 => 6.4

CFP: 2.6 => 2.9WFP: 3.7 => 4.6

CFP: 5.8WFP: 7.4

CFP: 6.1 => 4.9WFP: 7.9 => 6.7

CFP: 6.0 => 5.3WFP: 8.2 => 7.3

CFP: 5.1 => 4.2WFP: 6.8 => 5.7

CFP: 4.7 => 4.7WFP: 6.7 => 6.3

CFP: 4.4 => 4.0WFP: 5.9 => 5.7

CFP: 2.2 => 2.7WFP: 3.5 => 3.9

(t)

T

T

S

S

S

T

S

(s)

(s)

Characteristic Facial Pain (CFP) and Worst Facial Pain (WFP)Start of period value => End of period value

Continuing tx oval

Legend

TCM solid

Allocated tx square

Allocations

T = TCM

S = Self Care

Continuations (t) = TCM (s) = Self CareSC dashed

Figure 2. This figure illustrates the main short-term outcomes based on protocol-specified analyses for the primary outcomes, CFPandWFP. The statistical analysis that corresponds to the overall changes is provided in Table 4. Note that the facial pain values to theleft of the arrow for each group represent values at the start of that period, not at study baseline.

Ritenbaugh et al The Journal of Pain 1085

weredetermined tobe related to any study activities. Theblood work collected to evaluate any adverse impacts ofherbal treatment demonstrated no episodes of adverseeffects.

Discussion

Existing Treatment Strategies for TMDPain relief, sought mainly via biomedical approaches,

is the primary therapeutic objective of TMD treatmentsfor both patients and clinicians.15,25,33,52 The mostcommon of these conventional treatments areanalgesic, anti-inflammatory, antidepressant, and otherchronic pain medications—all in use among our partici-

pants. Our study implemented a brief psychosocial inter-vention (SC) modified from that evaluated by Dworkinet al16 that had been developed for psychosociallyfunctional patients, utilizing SC with no accompanyingusual care. This was efficacious in their patientpopulation, with significant reductions over short- orlong-term follow-up for pain and pain-related interfer-ence with daily activities.16-18,22,28 Although we hadanticipated recruiting a psychologically functionalpopulation, in fact our study population includedpsychosocially dysfunctional participants as well. TheSC strategy was shown to be successful for thepsychosocially functional participants within our studypopulation, especially for those with moderate painlevels at baseline (ss).

Figure 3. This figure illustrates the percent of allocated participants achieving clinically meaningful response ($30% improvement)through 16 weeks on study intervention (weeks 2–18). Left side of panel: Change for patients with high pain levels at baseline andallocated at first point (Tt allocated to TCM at initial time and continued; SS allocated to SC and then allocated to SC again; ST allo-cated to SC and then allocated to TCM). Right side of panel: Change for patients with lower (moderate) pain levels (s) at baseline (sSwith moderate baseline pain and allocated at week 8 to SC; sTwith moderate baseline pain and allocated at week 8 to TCM). Samplesizes for each group are shown in Fig 1.

1086 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

Whole Systems TCM CareThe present trial is 1 of only a small number of RCTs

designed to assess effectiveness of multiple modalities ofTCM. In relation to seasonal allergic rhinitis, 2 differentresearch teams have evaluated the combined use ofacupuncture and Chinese herbal therapy.10,54 Onecompared a standardized herbal formula alone to herbswith semistandardized acupuncture, tailored to TCMdiagnosis; the other compared semistandardizedacupuncture plus herbs tailored to TCM diagnosis tosham versions of each. Both studies incorporated designfeatures that moved them in the direction of real-worldcare. However, we are aware of none besides our ownthat have evaluated whole system TCM for any chronicpain condition.The present trial was designed to bring more compre-

hensive versions of clinical practice into research, fromboth the TCM and medical pain clinic perspectives. TCMpractitioners had the freedom to individually tailordifferentiation-specific herbal formulae from an FDA-approved list of 65 herbs. They also had considerablelatitude in creating tailored acupuncture protocols withinguidelines, and in the use of Chinese massage (Tuina),a technique often found appropriate for musculoskeletalconditions like TMD. Further, as a lesson learned from ourpilot study, participants were allowed the choice, in con-sultation with their practitioner, about how to space theirtreatment visits. Finally, from the pain clinic perspective,the stepped-care design provided the chance for partici-pants not receiving adequate benefit from biomedicalcare to explore TCM as a therapeutic option.

Comparative Effectiveness ResearchThis trial was designed with the intent of conforming

to current views of CER, including the comparison of 2viable clinical approaches, measuring outcomes that

are important to patients (WFP, CFP, and disability), al-lowing the practitioners flexibility in tailoring the ther-apy to the patient, assessment of benefits and harms,and including participants who are typical of thosewho would be seen in a pain clinic.27 Most importantly,the design allowed for changing the therapeutic ap-proach based on the patient’s response, as would bethe case in ordinary clinical practice but is rarely thecase in controlled trials. The analysis presented herewas for relatively short-term outcomes (8 and 16 weeks),but in a separate report we will assess longer-term (18month) data. In our analysis we have also taken into con-sideration patient subgroups and examined their trajec-tories of response to the sequence of treatments theyreceived, again as would be done in real clinical practice.In all of these aspects, we attempted to take into consid-eration as many as possible of the important aspects oftreatment for this patient population. The aim was topresent a therapeutic face that was as close to reality ascould be done in a research setting, based on findingsfrom a previous study.45 While there are inherent limita-tions to how closely a research study can parallel real-world practice, we believe we have shown that stepstoward the CER standards can be taken.

Lessons From Study ImplementationWhereas our prior trial recruited participants as they

were referred to a tertiary care TMD specialty clinic, thecurrent study relied on community outreach for partici-pant recruitment, with the TCM component included inthe outreach description. Counter to expectations, ourrecruitment pool had higher pain levels than seen inmany tertiary care settings, higher levels of psychosocialimpairment as measured by the RDC-TMD Axis II GradedChronic Pain Scale than the SC intervention was origi-nally intended to manage, and far less prior treatment.

Ritenbaugh et al The Journal of Pain 1087

Interviews with enrolled participants revealed a com-monly expressed opposition to or inability to afford themedications or interventions that they had previouslybeen offered, and the choice instead to just live withthe pain. In many cases, they preferred CAM therapiesbut had not been able to afford them either, and wereenthusiastic about an opportunity to participate in thisstudy. With regard to generalizability of the presentfindings it must be considered that CAM trials, like otherclinical trials, are likely to recruit individuals who are in-terested in the therapy being evaluated. In the presentcase, the advantage is that this is the population drawnto TCM, which is the population for which the trial is rel-evant; conversely, this may also be a population thatmight not choose a cognitive behavioral therapy-basedpsychosocial treatment intervention.

Study LimitationsLimitations come from ways in which the study design

did not/could not replicate clinical practice. Although wetook a step toward clinical practice, the decision of whichtherapy the participant would receive, and when, wasbased in the trial allocationprocess thatwasonly partly re-sponsive to participant needs and did not permit partici-pant choice. We did not tell participants that all thosewho continued to have substantial pain would ultimatelyget TCM, as we were concerned that such informationmight affect the reported pain levels of participants eagerto receive TCM. But as a result, some of the participantswho were not allocated to TCM in the second allocationwere particularly discouraged. In addition, the SC inter-vention was not originally designed to be delivered toTMD patients showing high levels of psychosocial disabil-ity. The extent to which this affected response to SC bysome participants requires further investigation. These as-pects may have had some influence onwhich participantsfailed to provide follow-up information.The modest results presented here provide informa-

tion only on short-term outcomes and do not includesubgroup analyses. However, TCM may provide greaterbenefits withmore treatment visits, and long-termmain-tenance issues are of great importance in chronic recur-ring conditions such as TMD. Cognitive behavioraltherapy interventions, at least, have been found effica-cious in long-term studies.35 The long-term componentof our trial, following participants through and beyond20 TCM treatments, will shed light on the long-term im-pact of TCM alone and on TCM preceded by SC. In addi-tion, the long-term analyses will include the evaluationof variations in outcomes by TMD subgroups, and by var-iations in the TCM treatments delivered. However, thedesign did not include sending those who had com-pleted TCM treatment without SC (Tt) to SC after TCM,which limits conclusions on the value of SC after TCM.This is an appropriate design feature for a future PhaseIII trial.

ConclusionsThe real-world clinic aim addressed in the present

trial was to identify effective treatment strategies for

patients presenting with different levels of TMD pain.The approach taken here was to continue participantson SC as long as their pain levels were below presetlimits, but if pain levels were higher, to test continua-tion of SC against a switch to TCM. The implication ofthis design is that participants with moderate or lowpain levels would remain on SC, which was designedfor this type of patient, while among those not improv-ing on SC, the 2 conditions (continue SC, change toTCM) would be tested in a conventional fashion. Thus,a key feature of our study was to evaluate the effectof TCM on patients for whom SC was not originallydesigned.The results of our trial suggest that the stepped-care

approach is an effective treatment strategy (Table 4).The present results can provide assurance to cliniciansthat TMD patients referred for TCM in a community-based model will receive treatment that is safe and islikely to provide short-term relief of pain and improvedquality of life. The long-term outcomes of this study, tobe presented separately, will provide a more completepicture of the impact of the different treatment trajecto-ries.In clinical practice for chronic pain, it is rare that pa-

tients only receive a single therapy over time. Thus, thisdesign, which is built on a functioning pain clinic model,can help to inform clinical decision making about poten-tial care trajectories. Further, the fact that we could carryout this type of design, already in use in behavioral med-icine research32 among patients with substantial pain,may help to inform clinical effectiveness research designsfor other types of chronic pain.

AcknowledgmentsWe thank our project officer, Partap Khalsa, DC, PhD,

for his ongoing involvement and support throughoutthe project, and critical help in the drafting of this pa-per, and Richard Nahin, PhD, MPH, for believing inthis novel design and supporting us through initialNCCAM hurdles. In relation to the interventions, wethank: Kimberly Huggins, RDH, BS, for her involvementin the modification of the self-care intervention, train-ing of practitioners and dentists, and ongoing support;Heather Tick, MD, and Andrew Shatte, PhD, for all as-pects of the Period 2 self-care intervention; and ourTCM practitioners (Tucson: Linda Stone, Carolyn Shen-men, Leslie Romero, Leslie McGee, Alex Holland; Port-land: Zheng Gong, Yan Liu, Ed Chiu, Cita Oudijk, MarkGoldby) for their willingness to fully collaborate. Wethank our project managers and staff, Cheryl Glass,Joshua Metlyng, Julie West, and Emery Eaves; our post-doctoral fellow, Allison Hopkins, PhD; and our Tucsonmedical director, Ed Paul, MD, for their help thatmade this possible. Finally, we particularly thank ourDSMB for their assistance and involvement in designand implementation and their careful considerationfor the safety of our participants throughout this com-plex project, and the initial reviewers of this article fortheir helpful comments.

1088 The Journal of Pain Chinese Medicine Versus Psychosocial Care for TMD

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