Paradoxes in Paradoxes in Acupuncture Acupuncture

Research: Strategies Research: Strategies for Moving Forwardfor Moving Forward

SAR White Paper Identifying SAR White Paper Identifying Acupuncture Research Confounding Acupuncture Research Confounding

FactorsFactors

Two Types of Acu ResearchTwo Types of Acu Research

Clinical Trials where a Clinical Trials where a modality is tested in a modality is tested in a real world settingreal world setting How does it perform?How does it perform? How does it perform How does it perform

compared to usual care?compared to usual care? How does it perform How does it perform

compared to sham?compared to sham?

Basic science research:Basic science research: what happens in the what happens in the

body when a needle is body when a needle is inserted?inserted?

What is the mechanism What is the mechanism with which acu works?with which acu works?

There is mounting evidence There is mounting evidence that acupuncture treatments that acupuncture treatments are superior to usual care for are superior to usual care for

some chronic pain some chronic pain conditions.conditions.

How does acu compare to usual How does acu compare to usual mainstream care?mainstream care?

German Low Back Pain study with 1162 German Low Back Pain study with 1162 patients: acu almost twice as effective as patients: acu almost twice as effective as mainstream care mainstream care

Seattle Low Back Pain study with 640 Seattle Low Back Pain study with 640 patients: 60% of acu patents had clinical patients: 60% of acu patents had clinical improvements compared to 39% mainstream improvements compared to 39% mainstream care.care.

University of MD study showed acu University of MD study showed acu significantly reduced pain and improved significantly reduced pain and improved function for OA of knee.function for OA of knee.

Acu compared to usual care:Acu compared to usual care:

Chronic headache patients used 15% less Chronic headache patients used 15% less meds, made 25% fewer visits to gp’s, took meds, made 25% fewer visits to gp’s, took 15% fewer sick days than control group 15% fewer sick days than control group (Vickers, et (Vickers, et

al, 2004);al, 2004);

Chronic neck pain: acu was superior to no acu Chronic neck pain: acu was superior to no acu at the end of 3 months (avg. 15 sessions) at the end of 3 months (avg. 15 sessions) (Witt et (Witt et

al 2006a)al 2006a)

Is Acu cost effective?Is Acu cost effective?

When added to usual care, is the benefit worth When added to usual care, is the benefit worth the additional cost?the additional cost?

How do the outcomes and costs of “stand How do the outcomes and costs of “stand alone” acu compare to usual care?alone” acu compare to usual care?

What is the cost incurred in improving the What is the cost incurred in improving the quality of life (Quality Adjusted Life Year)/quality of life (Quality Adjusted Life Year)/

Very few studies look at this, but it is a Very few studies look at this, but it is a calculation that our patients makecalculation that our patients make

Basic Science Research:Basic Science Research:

Acu-induced clinical improvements in chronic Acu-induced clinical improvements in chronic pain and carpal tunnel syndrome correlate with pain and carpal tunnel syndrome correlate with changes in brain activity.changes in brain activity.Harris, et al 2006, newberg et al 2005Harris, et al 2006, newberg et al 2005

Ultrasonic stim of points activated the brain in Ultrasonic stim of points activated the brain in the same way as needles, with no pain.the same way as needles, with no pain. Jones, 1998 Jones, 1998

The diffusion of a radioisotope injected at The diffusion of a radioisotope injected at acupoints showed the meridian pathway.acupoints showed the meridian pathway. Vernegeol Vernegeol

et al 1985et al 1985

Science, cont’dScience, cont’d

Undetermined whether traditional sensory Undetermined whether traditional sensory indications of acu points correlate with indications of acu points correlate with specific brain regions specific brain regions both positive and negative findingsboth positive and negative findings

Evidence of hormonal involvement:Evidence of hormonal involvement: Time course of acu analgesia is consistent with Time course of acu analgesia is consistent with

humoral rather than neural mediationhumoral rather than neural mediation Electro-acu releases endogenous opioids Electro-acu releases endogenous opioids

(difference between high and low frequencies)(difference between high and low frequencies)

Science, cont’dScience, cont’d

Just released research shows acupuncture Just released research shows acupuncture significantly reduces levels of a protein in rats significantly reduces levels of a protein in rats linked to chronic stresslinked to chronic stress

* Gaps in current knowledge that affect affect acu research

* Strategies to resolve the paradoxes that the research has

highlighted

Research results:Research results:

Overall acupuncture treatments are, at most, Overall acupuncture treatments are, at most, marginally more effective than shammarginally more effective than sham

Sham acu treatments are more effective than Sham acu treatments are more effective than conventional placebos when compared to no conventional placebos when compared to no treatmenttreatment

No evidence which part of acu treatments are No evidence which part of acu treatments are therapeutic (new meta analysis sheds more therapeutic (new meta analysis sheds more light - see discussion below)light - see discussion below)

Two ParadoxesTwo Paradoxes

1) A large number of 1) A large number of clinical trials show that clinical trials show that true acu is superior to true acu is superior to usual care, but does not usual care, but does not outperform sham acuoutperform sham acu

2) Research has shown 2) Research has shown physiologic effects vary physiologic effects vary as a function of as a function of needling (insertion needling (insertion depth, stimulation) but depth, stimulation) but not how that influences not how that influences therapeutic outcomestherapeutic outcomes

What Constitutes an Acu What Constitutes an Acu Treatment?Treatment?

Needling componentsNeedling components Diagnosis Diagnosis PalpationPalpation Belief and Expectancy Belief and Expectancy

of practitioner and of practitioner and patientpatient

Therapeutic settingTherapeutic setting TimeTime Attention of the Attention of the

PractitionerPractitioner Rapport between Rapport between

Practitioner and PatientPractitioner and Patient

Sham AcupunctureSham Acupuncture

Aim is to perform a mock treatment that the Aim is to perform a mock treatment that the subject believes is an acupuncture treatment, subject believes is an acupuncture treatment, but which is missing all relevant needling and but which is missing all relevant needling and non-needling “active” components. non-needling “active” components.

Components that have been Components that have been controlled for:controlled for:

needle/point locationneedle/point location

degree of needle degree of needle insertioninsertion

needle stimulationneedle stimulation

interaction with interaction with practitionerpractitioner

Acupuncture PointsAcupuncture Points

Research has shown considerable variability Research has shown considerable variability in the precise location of points across in the precise location of points across practitionerspractitioners

Little scientific evidence to support the Little scientific evidence to support the distinction between acu and non-acu points*distinction between acu and non-acu points*

Limited research on their bio-electric Limited research on their bio-electric properties and anatomical correlationsproperties and anatomical correlations

This lack of understanding of what is and what is not an acu point impacts our ability to interpret the results of clinical trials that

compare needling at acu and nonacu (sham) points.

Acu related terms are not well Acu related terms are not well defined, and have created defined, and have created

confusion and impeded progress confusion and impeded progress in research.in research.

Clarification of TermsClarification of Terms

Clarity is needed in describing the treatment: just Clarity is needed in describing the treatment: just needling, or a multi-component treatment that needling, or a multi-component treatment that involves history taking, physical exams, diagnosis, involves history taking, physical exams, diagnosis, and education and non-needling procedures such and education and non-needling procedures such as laser, TENS, heat lamps, etc.as laser, TENS, heat lamps, etc.

4 components of Acu treatment4 components of Acu treatment

Needling components (needle size, depth, stimulation, Needling components (needle size, depth, stimulation, location)location)

Specific theory-related, nonneedling components such as Specific theory-related, nonneedling components such as palpation and moxapalpation and moxa

Specific “psychological” components such as history Specific “psychological” components such as history taking, diagnosis, educationtaking, diagnosis, education

Generic non-needling components that are not unique to Generic non-needling components that are not unique to acu, such as belief and expectation, attention, timeacu, such as belief and expectation, attention, time

Paradox 1:(true acu performs Paradox 1:(true acu performs only slightly better than sham only slightly better than sham

acu) acu) Verum and sham treatments are equivalent, Verum and sham treatments are equivalent,

because the therapeutic effects of both are due because the therapeutic effects of both are due to nonspecific effectsto nonspecific effects

Specific therapeutic effects do exist, but are Specific therapeutic effects do exist, but are not detected in sham-controlled trials becausenot detected in sham-controlled trials because Sham acu is not inertSham acu is not inert Verum acu is less than optimalVerum acu is less than optimal

Paradox 2: it is unclear to what Paradox 2: it is unclear to what extent needling procedures extent needling procedures influence clinical outcomesinfluence clinical outcomes

Laboratory research may not be applicable to Laboratory research may not be applicable to clinical researchclinical research

Some of the physiological effects are not Some of the physiological effects are not related to therapyrelated to therapy

Needling effects could be small compared to Needling effects could be small compared to effects of other componentseffects of other components

Paradox 2, cont’d.Paradox 2, cont’d.

Sham controlled trials are problematic Sham controlled trials are problematic becausebecause The influence of needling techniques is poorly The influence of needling techniques is poorly

understood, andunderstood, and Objective bio-markers relative to commonly Objective bio-markers relative to commonly

treated conditions are lacking.treated conditions are lacking.

Future ResearchFuture Research

Clarify terms and maintain clarity when Clarify terms and maintain clarity when describing methodsdescribing methods

Clinical approaches need to understand acu Clinical approaches need to understand acu treatments as complex interventionstreatments as complex interventions

Recommendations for Future Recommendations for Future ResearchResearch

• Use clinical experience to identify key components specific to acu and to systematically study their therapeutic effects as well as their effects on physiology.

• Use clearly defined controls designed to test the specific component being evaluated (needle location, depth, etc.)

• This will lead to a clearer understanding of how to create sham protocol.

Possible Clinical StudiesPossible Clinical Studies

What components of acu treatment, other than What components of acu treatment, other than needling, are of most importance?needling, are of most importance?

Use medical imaging and biomarkers to Use medical imaging and biomarkers to evaluate the physiological effectsevaluate the physiological effects

Possible Studies cont’dPossible Studies cont’d

Use qualitative methods to explore the Use qualitative methods to explore the acupuncture processacupuncture process

Compare whole systems of CAM and Compare whole systems of CAM and biomedical interventions that reflect real-world biomedical interventions that reflect real-world practicepractice

Once effectiveness is demonstrated, future Once effectiveness is demonstrated, future trials can explore the components.trials can explore the components.

Possible studies, cont’dPossible studies, cont’d

Through studies, improve the consensus Through studies, improve the consensus regarding diagnosis and treatment of particular regarding diagnosis and treatment of particular conditions. This systemic study could identify conditions. This systemic study could identify an optimal protocol for a specific condition, an optimal protocol for a specific condition, based on both biomedical and traditional based on both biomedical and traditional diagnostic techniques. diagnostic techniques.

Possible “science” studiesPossible “science” studies

Improve understanding of “point specificity”, Improve understanding of “point specificity”, by including non-acu point controls along by including non-acu point controls along similar nerves.similar nerves.

What are the physiological responses to What are the physiological responses to acupuncture points and non-acu points. Do acupuncture points and non-acu points. Do acu points have distinct histological and/or acu points have distinct histological and/or biochemical characteristics?biochemical characteristics?

Possible “science” research, Possible “science” research, cont’dcont’d

Studies to identify the physiological effects Studies to identify the physiological effects associated with individual components of acu, associated with individual components of acu, both needling and non-needling.both needling and non-needling.

Studies to assess the physiological effects of Studies to assess the physiological effects of nonspecific needling and treatment nonspecific needling and treatment components.components.

Possible ‘science” research, Possible ‘science” research, cont’dcont’d

Studies to examine the effects of verum and Studies to examine the effects of verum and sham needling on local tissues and the nervous sham needling on local tissues and the nervous systemsystem

Determine the biomarkers that relate to a given Determine the biomarkers that relate to a given pathology and how they improve with pathology and how they improve with treatment.treatment.

Recommended research, cont’dRecommended research, cont’d

In order to assess effective needling, determine In order to assess effective needling, determine the biomarkers and clinical outcome measures the biomarkers and clinical outcome measures of both immediate and delayed physiologic of both immediate and delayed physiologic responses (e.g., pulses and brain activation responses (e.g., pulses and brain activation patterns) patterns)

Designing Appropriate ControlsDesigning Appropriate Controls

What to mimicWhat to mimic

For example, retractable For example, retractable needlesneedles

What to avoidWhat to avoid

For example, “active” For example, “active” needling, once it is needling, once it is knownknown

In conclusion:In conclusion:

Acupuncture research must include Acupuncture research must include both “top down” and “bottom up” both “top down” and “bottom up”

approachesapproaches

Top Down: acu Top Down: acu treatments as treatments as multicomponent “whole multicomponent “whole system” interventions, system” interventions, compared to “usual compared to “usual care”care”

Bottom Up: mechanistic Bottom Up: mechanistic studies that focus on studies that focus on understanding understanding individual treatment individual treatment components and how components and how they translate into they translate into clinical outcomes. clinical outcomes.

Translational Acu Research Strategy

Translational process (T1) Translational process (T2)

Bench Patient Community

Animal ExperimentsHuman Subject experiments

Controlledclinical trials

Survey researchCost effectivenessresearch

Basic scienceInformed approaches

Clinical practice-Informed approaches

These approaches will deepen These approaches will deepen our understanding of complex our understanding of complex

systems of care.systems of care.

We must remember to build We must remember to build clinical relevance into the design clinical relevance into the design of clinical as well as basic science of clinical as well as basic science

research.research.

Unique Considerations in Fertility TreatmentUnique Considerations in Fertility TreatmentTo help inform future research on fertility acupuncture, Cochrane et al analyzed responses To help inform future research on fertility acupuncture, Cochrane et al analyzed responses from ten fertility acupuncturists to define how best to treat fertility. The researchers used a from ten fertility acupuncturists to define how best to treat fertility. The researchers used a

complex consensus-building technique in this qualitative study that spanned two phases. complex consensus-building technique in this qualitative study that spanned two phases. Three acupuncturists were intensely interviewed in phase one to generate enough material to Three acupuncturists were intensely interviewed in phase one to generate enough material to

guide a forum in the second phase. Seven more acupuncturists were recruited, and during guide a forum in the second phase. Seven more acupuncturists were recruited, and during second phase, all ten participants discussed the themes and responses from the first phase second phase, all ten participants discussed the themes and responses from the first phase and then a questionnaire was developed and distributed. Participants were asked to rank and then a questionnaire was developed and distributed. Participants were asked to rank

statements according to relevance. The participants felt the following to be highly relevant: statements according to relevance. The participants felt the following to be highly relevant: acupuncture should not be limited to needling but include more aspects of TCM like diet, acupuncture should not be limited to needling but include more aspects of TCM like diet,

therapeutic relationship, etc. (7 of 10). When asked "Fertility acupuncture should be a therapeutic relationship, etc. (7 of 10). When asked "Fertility acupuncture should be a specialist endeavor requiring . . .," the participants felt it highly relevant that fertility specialist endeavor requiring . . .," the participants felt it highly relevant that fertility

acupuncturists should have knowledge of traditional Chinese medicine (TCM) gynecology (9 acupuncturists should have knowledge of traditional Chinese medicine (TCM) gynecology (9 of 10), and knowledge of ART procedures (8 of 10) and reproductive endocrinology and of 10), and knowledge of ART procedures (8 of 10) and reproductive endocrinology and

physiology (7 of 10), as well as capable of engaging the patient-practitioner relationship (7 of physiology (7 of 10), as well as capable of engaging the patient-practitioner relationship (7 of 10). Additionally, participants felt the TCM pattern (6 of 10), state of the Shen (5 of 10) and 10). Additionally, participants felt the TCM pattern (6 of 10), state of the Shen (5 of 10) and

the timing of treatment (4 of 10) as highly relevant in guiding treatment. Biomedical the timing of treatment (4 of 10) as highly relevant in guiding treatment. Biomedical diagnosis (6 of 10) and menstrual cycle phases (6 of 10) were rated as relevant in guiding diagnosis (6 of 10) and menstrual cycle phases (6 of 10) were rated as relevant in guiding

treatment.treatment.

[Source: Cochrane S, Smith CA, Possamai-Inessedy A. Development of a fertility [Source: Cochrane S, Smith CA, Possamai-Inessedy A. Development of a fertility acupuncture protocol: defining acupuncture treatment protocol to support and treat women acupuncture protocol: defining acupuncture treatment protocol to support and treat women

experiencing conception delays. J Altern Complement Med. 2011. 17(4):329-337. experiencing conception delays. J Altern Complement Med. 2011. 17(4):329-337. http://www.ncbi.nlm.nih.gov/pubmed/21495903 ]http://www.ncbi.nlm.nih.gov/pubmed/21495903 ]

This strategy will result in a This strategy will result in a broader and stronger basis of broader and stronger basis of

support for the study of support for the study of acupuncture and other complex acupuncture and other complex

treatments.treatments.

New Meta-Analysis of Acu for New Meta-Analysis of Acu for Chronic PainChronic Pain

Sheds light on some of these outstanding Sheds light on some of these outstanding questionsquestions

See next Power Point for details!See next Power Point for details!