AcupuAcupuncture for ncture for Chronic PainChronic Pain

Individual Patient Data Meta-Individual Patient Data Meta-AnalysisAnalysis

Presentation prepared by Heidi MostPresentation prepared by Heidi Most

AuthorsAuthors

Andrew Vickers, D.Phil; A. Cronin, MS; A. Andrew Vickers, D.Phil; A. Cronin, MS; A. Mashino, BS; G. Lewith, MD; H. Mashino, BS; G. Lewith, MD; H. MacPherson, PhD; N. Foster D.Phil; K MacPherson, PhD; N. Foster D.Phil; K Sherman, PhD; C. Witt, MD; K. Linde, MDSherman, PhD; C. Witt, MD; K. Linde, MD

Well known researchers in the acu field, Well known researchers in the acu field, who have themselves been conducting who have themselves been conducting studies for many years.studies for many years.

Past Acupuncture ResearchPast Acupuncture Research

Often poor quality studiesOften poor quality studies Multi-modal interventionsMulti-modal interventions Many show acu better than no-acu, acu Many show acu better than no-acu, acu

better than usual care (for low back pain, better than usual care (for low back pain, osteo-arthritis of the knee, etc)osteo-arthritis of the knee, etc)

But few show true acu better than sham But few show true acu better than sham acu; often point selection or point acu; often point selection or point placement doesn’t make a differenceplacement doesn’t make a difference

Sham AcuSham Acu

Acu needle used on point close to but not Acu needle used on point close to but not exactly at the real acu pointexactly at the real acu point

Acu is done on entirely different pointsAcu is done on entirely different points Needle is not inserted/ or toothpick is used Needle is not inserted/ or toothpick is used

to press but not pierce pointto press but not pierce point

Confounding factorsConfounding factors

Perhaps any insertion of needles has Perhaps any insertion of needles has physiological effectphysiological effect

Perhaps any stimulation of points has Perhaps any stimulation of points has physiological effectphysiological effect

Perhaps keeping study blinded was Perhaps keeping study blinded was impossibleimpossible

Perhaps ritual of acupuncture is powerfulPerhaps ritual of acupuncture is powerful

This StudyThis Study

Identified high quality RCTs of acu for Identified high quality RCTs of acu for chronic painchronic pain

Used individual patient data from each trial, Used individual patient data from each trial, as opposed to combining summary dataas opposed to combining summary data Enhanced data qualityEnhanced data quality Enabled different forms of outcome to be Enabled different forms of outcome to be

combinedcombined Allowed use of statistical techniques of Allowed use of statistical techniques of

increased precisionincreased precision

Study had 3 phasesStudy had 3 phases

ID of eligible RCTs - no language ID of eligible RCTs - no language restrictionsrestrictions

Collection, checking and harmonization of Collection, checking and harmonization of raw dataraw data

Individual patient data meta-analysisIndividual patient data meta-analysis

Study SelectionStudy Selection

RCTs included at least 1 group receiving RCTs included at least 1 group receiving true acu and 1 either sham or no acu true acu and 1 either sham or no acu control.control.

Only trials for nonspecific back or neck Only trials for nonspecific back or neck pain, shoulder pain, chronic headache, or pain, shoulder pain, chronic headache, or osteoarthritis of at least 4 weeks duration.osteoarthritis of at least 4 weeks duration.

Primary end point must be measured more Primary end point must be measured more than 4 weeks after initial acu treatmentthan 4 weeks after initial acu treatment

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Data Synthesis and AnalysisData Synthesis and Analysis

““Each RCT was reanalyzed by analysis of Each RCT was reanalyzed by analysis of covariance with the standardized principal covariance with the standardized principal end point as the dependent variable, and end point as the dependent variable, and the baseline measure of the principal end the baseline measure of the principal end point and variables used to stratify point and variables used to stratify randomization as covariates….” randomization as covariates….”

ETC!!!ETC!!!

Study Study

31 out of 82 RCTs were eligible31 out of 82 RCTs were eligible Sham included acu needles inserted Sham included acu needles inserted

superficially, or sham acu devices with needles superficially, or sham acu devices with needles that retract, and don’t penetrate, and no needle that retract, and don’t penetrate, and no needle approachesapproaches

Con-interventions varied:Con-interventions varied: No additional treatments other than some analgesics No additional treatments other than some analgesics

or both acu and sham received additional treatment or both acu and sham received additional treatment such as exercisesuch as exercise

No-acu controls included usual care (education, No-acu controls included usual care (education, attention control, drugs) or wait-listattention control, drugs) or wait-list

Study, cont’dStudy, cont’d

17,922 patients (US, UK, Germany, Spain, 17,922 patients (US, UK, Germany, Spain, Sweden); 29 RCTsSweden); 29 RCTs

Included only high quality RCTsIncluded only high quality RCTs Obtained raw data for individual patient Obtained raw data for individual patient

data meta-analysisdata meta-analysis

Meta-AnalysisMeta-Analysis

Forest plots for acu against sham acu and Forest plots for acu against sham acu and against no acu controls are show against no acu controls are show separately for each of the 4 pain separately for each of the 4 pain conditionsconditions

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ResultsResults

Acu was statistically superior to control for Acu was statistically superior to control for all analyses (P<.001)all analyses (P<.001) Effect was larger for acu/no-acu than for Effect was larger for acu/no-acu than for

acu/shamacu/sham In real terms; a baseline pain score for a In real terms; a baseline pain score for a

typical RCT might be 60 out of 100. With typical RCT might be 60 out of 100. With standard deviation of 25standard deviation of 25 Follow up scores might be 43 in no acu; 35 in Follow up scores might be 43 in no acu; 35 in

sham and 30 in true acu. sham and 30 in true acu.

Results cont’dResults cont’d

If responses were defined in terms of a If responses were defined in terms of a pain reduction of 50% or more, response pain reduction of 50% or more, response rates would be approximately 30% for no rates would be approximately 30% for no acu; 42.5% for sham, and 50% for true.acu; 42.5% for sham, and 50% for true.

Many analyses doneMany analyses done

Several prespecified sensitivity analyses - Several prespecified sensitivity analyses - little impact on primary analysislittle impact on primary analysis

Estimated impact of publication bias in two Estimated impact of publication bias in two different ways, with no significant impactdifferent ways, with no significant impact

Sensitivity analysis examined effect of Sensitivity analysis examined effect of pooling different end points measured at pooling different end points measured at different periods of follow-up - also no different periods of follow-up - also no effect on resultseffect on results

Overview of FindingsOverview of Findings

Found statistically significant differences Found statistically significant differences between both acu vs. sham and acu vs. between both acu vs. sham and acu vs. no-acu for all pain types no-acu for all pain types

Meta-analytic effect sizes were similar Meta-analytic effect sizes were similar across pain conditionsacross pain conditions

Overview of Findings, Cont’dOverview of Findings, Cont’d

Individual RCT effect sizes comparing acu Individual RCT effect sizes comparing acu with no acu did vary, according to type of with no acu did vary, according to type of control used.control used.

Acu had smaller benefit in patients who Acu had smaller benefit in patients who received a program of ancillary care (I.e. received a program of ancillary care (I.e. physical therapy) vs. usual carephysical therapy) vs. usual care

““Never the less…”Never the less…”

The average effect (meta-analytic estimate The average effect (meta-analytic estimate of .5 SD) is of clear clinical relevance as of .5 SD) is of clear clinical relevance as either standardized difference or as a pain either standardized difference or as a pain scalescale

Difference between acu and sham is less Difference between acu and sham is less (.15 to .23 SD)(.15 to .23 SD)

Study limitationsStudy limitations

Sample size and quality were goodSample size and quality were good Impossible to blind acu and no-acu, but Impossible to blind acu and no-acu, but

this is true of all non-drug studiesthis is true of all non-drug studies Meta analyses combined different end Meta analyses combined different end

points, such as pain and function, points, such as pain and function, measured at different times…but analysis measured at different times…but analysis did not change when they restricted to did not change when they restricted to pain end points at a specific follow up pain end points at a specific follow up time.time.

It was a better study than It was a better study than othersothers

Others hadOthers had Liberal eligibility criteriaLiberal eligibility criteria Low methodological qualityLow methodological quality have not included meta-analyseshave not included meta-analyses

Also…Also…

More recent meta-analyses have More recent meta-analyses have comparable findings with clear differences comparable findings with clear differences between acu and no-acu, and smaller between acu and no-acu, and smaller differences between true and sham acudifferences between true and sham acu

They analyzed summary data rather than They analyzed summary data rather than individual patient data meta-analysis. individual patient data meta-analysis.

““Study demonstrated a robust Study demonstrated a robust difference between acu and difference between acu and

sham control that can be sham control that can be distinguished from bias.”distinguished from bias.”

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InterpretationInterpretation

Effects of acu are clinical relevantEffects of acu are clinical relevant Important part of these total effects is not due to Important part of these total effects is not due to

issues considered to be crucial by most issues considered to be crucial by most acupuncturists: Correct location of points and acupuncturists: Correct location of points and depth of needlingdepth of needling

Effects of acu over sham are small, but clinical Effects of acu over sham are small, but clinical decision is not between true and sham acu, but decision is not between true and sham acu, but between referral or non-referralbetween referral or non-referral

Interpretation cont’dInterpretation cont’d

““Total effects of acu include specific Total effects of acu include specific effects associated with correct needle effects associated with correct needle insertion, nonspecific physiologic effects of insertion, nonspecific physiologic effects of needling, and nonspecific psychological needling, and nonspecific psychological effects related to the patient’s belief that effects related to the patient’s belief that treatment will be effective.”treatment will be effective.”

Heidi’s reactionsHeidi’s reactions

On the one handOn the one hand

Acu effective Acu effective Many western Many western

interventions have interventions have strong placebo effect strong placebo effect so don’t need to be so don’t need to be defensivedefensive

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On the other hand...On the other hand...

Specific needling Specific needling location and depth location and depth shown not to have shown not to have effecteffect

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Questions left unansweredQuestions left unanswered

Were points chosen for each intervention Were points chosen for each intervention the best points?the best points?

Was diagnosis correct?Was diagnosis correct? Is the theory of point selection and point Is the theory of point selection and point

placement a sham, or is it simply not placement a sham, or is it simply not applied well?applied well?