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Acupuncture and the placebo question:
evidence on MSK pain, osteoarthritis and
headache
Hugh MacPherson
University of York, UK
2
“... any discipline whose practitioners make
specific claims ... to treat specific conditions
should have evidence ... above and beyond the
placebo effect“ (HoL Report 2000*)
*House of Lords, Science and Technology, Sixth Report, 2000 www/parliament.the-stationarey-office/co.uk/pa
The need to answer the
placebo question
Colquhoun D, Novella SP. Acupuncture Is Theatrical Placebo.
Anesthesia & Analgesia. 2013 Jun;116(6):1360–3.
Evidence hierarchy
Individual Patient Data
Meta-analysis
• A meta-analysis in which the analysis is by
patient not just by trial
– Increases statistical power
– Allows standardisation of analyses across trials
– Facilitates sub-group analyses
– Has been used for cancer and diabetes
– Requires effective research collaboration
What is an Individual Patient Data (IPD)
Meta-analysis?
Members of the
Acupuncture Trialists Collaboration
Claire Allen (patient rep.) Dominik Irnich Karen Sherman*
Mac Beckner Dr Wayne B. Jonas Hans Trampisch
Benno Brinkhaus Kai Kronfeld Jorge Vas
Hans-Christoph Diener Lixing Lao Andrew J. Vickers**
Brian Berman George Lewith Norbert Victor
Remy Coeytaux Klaus Linde* Peter White
Angel M. Cronin Dieter Melchart Lyn Williamson
Nadine Foster Albrecht Molsberger Stefan Willich
Michael Haake Hugh MacPherson* Claudia M. Witt*
Richard Hammerschlag Eric Manheimer
**Chair
*Steering Group
www.acupuncturetrialistscollaboration.org
Question 1: is acupuncture better
than sham (placebo)
acupuncture?
Question 2: is acupuncture better
than standard care, usual care,
waitlist, etc?
Key research questions asked by the
Acupuncture Trialists Collaboration
Inclusion criteria
• Randomised controlled trials (RCTs) of
acupuncture for chronic pain:
Headache/migraine
Osteoarthritis
Back & neck pain
• High quality: unambiguously concealed
random allocation
PRISMA flow diagram
ATC results
Raw data obtained from 29 trials with 17,922 patients:
20 trials with sham controls (5,230
patients)
18 trials with non-acupuncture controls
(14,597 patients)
Results for research question 1
Is acupuncture better than sham
Acupuncture varies across trials
Sham acupuncture controls vary:
Non-needle sham (e.g. inactive TENS)
Needle-based sham Penetrating needles
Non-penetrating needle
At acupuncture points
At non-acupuncture points
Acupuncture vs. Sham
Headache/migraine
Favours control ←→ Favours acupuncture
Acupuncture vs Sham (including outlier Vas trial)
Osteoarthritis pain
Favours control ←→ Favours acupuncture
Acupuncture vs Sham (including outlier Vas trials)
Musculo-skeletal pain (back and neck)
Favours control ←→ Favours acupuncture
Indication Effect size
(Fixed effects)
Acupuncture vs. Sham controls (excluding outliers)
Migraine/headache -0.15 (-0.24, -0.07) P<0.001
Osteoarthritis -0.16 (-0.25, -0.07) P<0.001
LBP & Neck Pain -0.23 (-0.33, -0.13) P<0.001
Negative values represent better outcomes
Values in parentheses are 95% confidence intervals
Individual patient data meta-analysis Acupuncture vs. Sham controls (n= 5,230)
Interpretation of effect sizes:
0.8 = LARGE
0.5 = MODERATE
0.3 = SMALL
Results for research question 2
Is acupuncture better than non-acupuncture controls
Acupuncture varies across trials
Non-acupuncture controls vary:
No treatment
Wait list
Attention control
Rescue medication
Usual care
Other standard treatment
Acupuncture vs. Non-acupuncture controls
Headache/migraine
Favours control ←→ Favours acupuncture
Acupuncture vs. Non-acupuncture controls
Osteoarthritis pain
Favours control ←→ Favours acupuncture
Acupuncture vs. Non-acupuncture controls:
Musculo-skeletal pain
Favours control ←→ Favours acupuncture
Individual patient data meta-analysis
Acupuncture vs. Sham controls, and
Acupuncture vs. Non-acupuncture controls (n= 14,597 )
Indication Effect size
(Fixed effects)
Acupuncture vs. Sham controls (excluding outliers)
Migraine/headache -0.15 (-0.24, -0.07) P<0.001
Osteoarthritis -0.16 (-0.25, -0.07) P<0.001
Back & Neck Pain -0.23 (-0.33, -0.13) P<0.001
Acupuncture vs. Non-acupuncture controls
Migraine/headache -0.42 (-0.46, -0.37) P<0.001
Osteoarthritis -0.57 (-0.64, -0.50) P<0.001
Back & Neck Pain -0.55 (-0.58, -0.51) P<0.001
Negative values represent better outcomes
Values in parentheses are 95% confidence intervals
Effect sizes: 0.8 = LARGE
0.5 = MODERATE
0.3 = SMALL
Vickers et al. Archives of Internal Medicine,
2012;172(19):1444-1453
…. “significant difference between true and
sham acupuncture indicate that
acupuncture is more than a placebo”
…. “Acupuncture is effective for the
treatment of chronic pain”
“It hardly matters whether it is correct that acupuncture
is better than sham ….
What really matters is that Vickers et al showed that the
difference is far too small to be of the slightest clinical
interest.”
Reference: David Colquhoun, BMJ 2012
http://www.bmj.com/content/345/bmj.e6060?tab=responses
Criticism: What about the size of the
clinical effect?
NSAIDs are the commonly prescribed for
chronic pain
NSAIDs vs. placebo for pain reduction have
similar effect sizes: 0.23 (0.15 to 0.31)
(Bjordal et al BMJ 2004)
NSAIDs have worse safety profile
[in UK 2,000 deaths a year from people
taking NSAIDS for more than 2 months]
(Tramer et al Pain 2000)
Criticism: What about the size of the
clinical effect?
Interpretation for sample sizes
needed for trials in population
*Number needed to show a difference, if one existed,
based on 90% power and 0.05 significance
Estimated
effect size
Approx sample
size* for a two-
arm trial
Medium 0.5 170
Small 0.3 468
True vs. sham
acupuncture
0.2 1,052
Acu style 1 vs.
Acu style 2
0.1 4,204
ATC sub-studies:
1. What characteristics of acupuncture are
associated with better/worse outcome
2. How does the choice of control impact on
effectiveness of acupuncture
3. Do some patients respond better than others,
and if so what are their characteristics?
4. Is there a subset of patients who are “super-
responders” to acupuncture?
5. What is the time course of acupuncture effects?
How long are benefits sustained?
6. How much variation in outcome is there between
practitioners?
MacPherson et al. (2013) PLoS ONE 8(10): e77438.
Sub-study 1: Variation by
acupuncture characteristic
Sub-study 2: Variation with different
types of control
MacPherson et al. (2014) PLoS ONE 9(4): e93739
Individual patient data
All trials “high quality”
Large patient numbers
Limited by the available studies
Limited data collected (?unknown unknowns)
Similarity of analysed studies (e.g. weekly
sessions)
Not enough trials
Limitations & Strengths
Final conclusion
• Acupuncture outperforms sham
– small effect size of ~0.2,
– statistically significant at p<0.001
– similar effect size to NSAIDs vs. placebo (and
safer)
• Acupuncture is effective for chronic pain
– Moderate effect size of ~0.5 (p<0.001) and
which is clinically relevant
Acknowledgments
The Acupuncture
Trialists’ Collaboration
is funded by an R21
(AT004189I) from the
National Center for
Complementary and
Alternative Medicine
(NCCAM) at the
National Institutes of
Health (NIH) to Dr
Vickers and by a grant
from the Samueli
Institute.
This research is
supported in part by the
National Institute for
Health Research (NIHR)
under Programme
Grants for Applied
Research (Grant No. RP-
PG-0707-10186). The
views expressed in this
presentation are those of
the author(s) and not
necessarily those of the
NHS, the NIHR or the
Department of Health.
1. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Victor N, et al.
Individual patient data meta-analysis of acupuncture for chronic pain: protocol of the
Acupuncture Trialists’ Collaboration. Trials. 2010;11:90.
2. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE, et al.
Acupuncture for Chronic Pain: Individual Patient Data Meta-analysis. ArchInternMed. 2012
Sep 10;172(19):1444–53.
3. Vickers AJ, Maschino AC, Lewith G, MacPherson H, Sherman KJ, Witt CM, et al.
Responses to the Acupuncture Trialists’ Collaboration individual patient data meta-analysis.
Acupunct Med. 2013 Mar;31(1):98–100.
4. MacPherson H, Maschino AC, Lewith G, Foster NE, Witt C, Vickers AJ, et al.
Characteristics of acupuncture treatment associated with outcome: an individual patient meta-
analysis of 17,922 patients with chronic pain in randomised controlled trials. PLoS ONE.
2013;8(10):e77438.
5. MacPherson H, Vertosick E, Lewith G, Linde K, Sherman KJ, Witt CM, et al.
Influence of Control Group on Effect Size in Trials of Acupuncture for Chronic Pain: A
Secondary Analysis of an Individual Patient Data Meta-Analysis. PLoS ONE. 2014 Apr
4;9(4):e93739.
6. Vickers AJ, Linde K. Acupuncture for chronic pain. JAMA. 2014 Mar 5;311(9):955–6.
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