Acupuncture for Chronic Pain Individual Patient Data Meta-Analysis Presentation prepared by Heidi Most

Authors Andrew Vickers, D.Phil; A. Cronin, MS; A. Mashino, BS; G. Lewith, MD; H. MacPherson, PhD; N. Foster D.Phil; K Sherman, PhD; C. Witt, MD; K. Linde, MD Well known researchers in the acu field, who have themselves been conducting studies for many years.

Past Acupuncture Research Often poor quality studies Multi-modal interventions Many show acu better than no-acu, acu better than usual care (for low back pain, osteo-arthritis of the knee, etc) But few show true acu better than sham acu; often point selection or point placement doesn’t make a difference

Sham Acu Acu needle used on point close to but not exactly at the real acu point Acu is done on entirely different points Needle is not inserted/ or toothpick is used to press but not pierce point

Confounding factors Perhaps any insertion of needles has physiological effect Perhaps any stimulation of points has physiological effect Perhaps keeping study blinded was impossible Perhaps ritual of acupuncture is powerful

This Study Identified high quality RCTs of acu for chronic pain Used individual patient data from each trial, as opposed to combining summary data Enhanced data quality Enabled different forms of outcome to be combined Allowed use of statistical techniques of increased precision

Study had 3 phases ID of eligible RCTs - no language restrictions Collection, checking and harmonization of raw data Individual patient data meta-analysis

Study Selection RCTs included at least 1 group receiving true acu and 1 either sham or no acu control. Only trials for nonspecific back or neck pain, shoulder pain, chronic headache, or osteoarthritis of at least 4 weeks duration. Primary end point must be measured more than 4 weeks after initial acu treatment

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

Study 31 out of 82 RCTs were eligible Sham included acu needles inserted superficially, or sham acu devices with needles that retract, and don’t penetrate, and no needle approaches Con-interventions varied: No additional treatments other than some analgesics or both acu and sham received additional treatment such as exercise No-acu controls included usual care (education, attention control, drugs) or wait-list

Study, cont’d 17,922 patients (US, UK, Germany, Spain, Sweden); 29 RCTs Included only high quality RCTs Obtained raw data for individual patient data meta-analysis

Meta-Analysis Forest plots for acu against sham acu and against no acu controls are show separately for each of the 4 pain conditions

Results Acu was statistically superior to control for all analyses (P<.001) Effect was larger for acu/no-acu than for acu/sham In real terms; a baseline pain score for a typical RCT might be 60 out of 100. With standard deviation of 25 Follow up scores might be 43 in no acu; 35 in sham and 30 in true acu.

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

Many analyses done Several prespecified sensitivity analyses - little impact on primary analysis Estimated impact of publication bias in two different ways, with no significant impact Sensitivity analysis examined effect of pooling different end points measured at different periods of follow-up - also no effect on results

Overview of Findings Found statistically significant differences between both acu vs. sham and acu vs. no-acu for all pain types Meta-analytic effect sizes were similar across pain conditions

Overview of Findings, Cont’d Individual RCT effect sizes comparing acu with no acu did vary, according to type of control used. Acu had smaller benefit in patients who received a program of ancillary care (I.e. physical therapy) vs. usual care

“Never the less…” The average effect (meta-analytic estimate of .5 SD) is of clear clinical relevance as either standardized difference or as a pain scale Difference between acu and sham is less (.15 to .23 SD)

Study limitations Sample size and quality were good Impossible to blind acu and no-acu, but this is true of all non-drug studies Meta analyses combined different end points, such as pain and function, measured at different times…but analysis did not change when they restricted to pain end points at a specific follow up time.

It was a better study than others Others had Liberal eligibility criteria Low methodological quality have not included meta-analyses

Also… More recent meta-analyses have comparable findings with clear differences between acu and no-acu, and smaller differences between true and sham acu They analyzed summary data rather than individual patient data meta-analysis.

“Study demonstrated a robust difference between acu and sham control that can be distinguished from bias.”

Interpretation Effects of acu are clinical relevant Important part of these total effects is not due to issues considered to be crucial by most acupuncturists: Correct location of points and depth of needling Effects of acu over sham are small, but clinical decision is not between true and sham acu, but between referral or non-referral

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

Heidi’s reactions

On the one hand Acu effective Many western interventions have strong placebo effect so don’t need to be defensive

On the other hand... Specific needling location and depth shown not to have effect

Questions left unanswered Were points chosen for each intervention the best points? Was diagnosis correct? Is the theory of point selection and point placement a sham, or is it simply not applied well?