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German Acupuncture Trials (GERAC) for Chronic Low Back Pain Randomized, Multicenter, Blinded, Parallel-Group Trial With 3 Groups


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To our knowledge, verum acupuncture has never been directly compared with sham acupuncture and guideline-based conventional therapy in patients with chronic low back pain. A patient- and observer-blinded randomized controlled trial conducted in Germany involving 340 outpatient practices, including 1162 patients aged 18 to 86 years (mean +/- SD age, 50 +/- 15 years) with a history of chronic low back pain for a mean of 8 years. Patients underwent ten 30-minute sessions, generally 2 sessions per week, of verum acupuncture (n = 387) according to principles of traditional Chinese medicine; sham acupuncture (n = 387) consisting of superficial needling at nonacupuncture points; or conventional therapy, a combination of drugs, physical therapy, and exercise (n = 388). Five additional sessions were offered to patients who had a partial response to treatment (10%-50% reduction in pain intensity). Primary outcome was response after 6 months, defined as 33% improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale questionnaire or 12% improvement or better on the back-specific Hanover Functional Ability Questionnaire. Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement. At 6 months, response rate was 47.6% in the verum acupuncture group, 44.2% in the sham acupuncture group, and 27.4% in the conventional therapy group. Differences among groups were as follows: verum vs sham, 3.4% (95% confidence interval, -3.7% to 10.3%; P = .39); verum vs conventional therapy, 20.2% (95% confidence interval, 13.4% to 26.7%; P < .001); and sham vs conventional therapy, 16.8% (95% confidence interval, 10.1% to 23.4%; P < .001. Low back pain improved after acupuncture treatment for at least 6 months. Effectiveness of acupuncture, either verum or sham, was almost twice that of conventional therapy.
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German Acupuncture Trials (GERAC)
for Chronic Low Back Pain
Randomized, Multicenter, Blinded, Parallel-Group Trial With 3 Groups
Michael Haake, PhD, MD; Hans-Helge Mu¨ller, PhD; Carmen Schade-Brittinger;
Heinz D. Basler, PhD; Helmut Scha¨fer, PhD; Christoph Maier, PhD, MD;
Heinz G. Endres, MD; Hans J. Trampisch, PhD; Albrecht Molsberger, PhD, MD
Background: To our knowledge, verum acupuncture
has never been directly compared with sham acupunc-
ture and guideline-based conventional therapy in pa-
tients with chronic low back pain.
Methods: A patient- and observer-blinded randomized
controlled trial conducted in Germany involving 340 out-
patient practices, including 1162 patients aged 18 to
86 years (mean±SD age, 50±15 years) with a history of
chronic low back pain for a mean of 8 years. Patients un-
derwent ten 30-minute sessions, generally 2 sessions per
week, of verum acupuncture (n=387) according to prin-
ciples of traditional Chinese medicine; sham acupunc-
ture (n=387) consisting of superficial needling at non-
acupuncture points; or conventional therapy, a
combination of drugs, physical therapy, and exercise
(n= 388). Five additional sessions were offered to pa-
tients who had a partial response to treatment (10%-
50% reduction in pain intensity). Primary outcome was
response after 6 months, defined as 33% improvement
or better on 3 pain-related items on the Von Korff Chronic
Pain Grade Scale questionnaire or 12% improvement or
better on the back-specific Hanover Functional Ability
Questionnaire. Patients who were unblinded or had re-
course to other than permitted concomitant therapies dur-
ing follow-up were classified as nonresponders regard-
less of symptom improvement.
Results: At 6 months, response rate was 47.6% in the
verum acupuncture group, 44.2% in the sham acupunc-
ture group, and 27.4% in the conventional therapy group.
Differences among groups were as follows: verum vs sham,
3.4% (95% confidence interval, −3.7% to 10.3%; P=.39);
verum vs conventional therapy, 20.2% (95% confidence
interval, 13.4% to 26.7%; P .001); and sham vs con-
ventional therapy, 16.8% (95% confidence interval, 10.1%
to 23.4%; P .001.
Conclusions: Low back pain improved after acupunc-
ture treatment for at least 6 months. Effectiveness of acu-
puncture, either verum or sham, was almost twice that
of conventional therapy.
Arch Intern Med. 2007;167(17):1892-1898
impairing, and disabling
condition, often long-term,
with an estimated lifetime
prevalence of 70% to 85%.
It is the second most common pain for
which physician treatment is sought and
a major reason for absenteeism and dis-
Considering direct and indirect
costs in terms of health care and lost pro-
ductivity, the annual cost of low back pain
to society is staggering.
National and international guidelines do
not recommend one treatment over an-
other. While many treatment methods have
been tried, including behavioral modifica-
tions, nonsteroidal anti-inflammatory drugs,
and physiotherapy, randomized con-
trolled trials have failed to demonstrate that
any of these is clearly more effective for re-
lieving pain or improving functional out-
Thus, acupuncture is increasingly
used as an alternative therapy. However, the
value of acupuncture for the treatment of
low back pain is still controversial. A re-
cent Cochrane review could only conclude
that acupuncture may be useful as an ad-
junct to other therapies.
To our knowl-
edge, no studies have directly compared acu-
puncture with guideline-based conventional
therapy. The German Acupuncture Trials
(GERAC) was designed to investigate
whether acupuncture is more efficacious in
reducing chronic low back pain than con-
ventional therapy or sham acupuncture.
The design of this multicenter, randomized trial
has been described.
Main inclusion criteria
were as follows: age 18 years or older, clinical
diagnosis of chronic low back pain for 6 months
or longer, mean Von Korff Chronic Pain Grade
of grade 1 or higher and a Hanover Func-
Author Affiliations: Orthopedic
Department, University of
Regensburg, Bad Abbach,
Germany (Dr Haake); Institutes
for Medical Biometry and
Epidemiology (Drs Mu¨ ller and
Scha¨fer) and Medical Psychology
(Dr Basler) and Centre for
Clinical Trials (Ms Schade-
Brittinger), Philipps-University
Marburg, Marburg, Germany;
Departments of Pain
Management, BG-Kliniken
Bergmannsheil (Dr Maier) and
Medical Informatics, Statistics
and Epidemiology,
Ruhr-University Bochum,
Bochum, Germany (Drs Endres
and Trampisch); and Centre for
Clinical Acupuncture and
Research, Du¨ sseldorf, Germany
(Dr Molsberger).
©2007 American Medical Association. All rights reserved.
at University College London, on September 25, 2007 www.archinternmed.comDownloaded from
tional Ability Questionnaire score of less than 70%,
no previ-
ous acupuncture for treatment of chronic low back pain, and
signed informed consent. Primary exclusion criteria were pre-
vious spinal surgery; previous spinal fractures, infectious, or
tumorous spondylopathy; and chronic pain caused by other dis-
(Table 1). Patients were made aware of the study through
newspapers, magazines, radio, and television. A list of physi-
cians participating in the randomized trials was available on
the Internet or could be requested from the medical insurance
companies or the study center. Only patients who had been
therapy-free for at least 7 days were eligible for screening.
Figure 1 shows participant progress through the study.
Acupuncture was administered in 340 outpatient practices
by physicians of various specializations who had at least 140
hours of acupuncture training: 55% had undergone basic train-
ing (mean, 213 hours) and 45% had advanced training (mean,
376 hours). The study physicians had practiced acupuncture
for 2 to 36 years (median, 8.0 years). All took part in a 1-day
training session with emphasis on acupuncture methods and
study design. Each patient in the study practices was seen by
the same physician-acupuncturist at each session. Indepen-
dent telephone interviewers assessed outcome measures.
The study was conducted in accord with International Con-
ference on Harmonization [of Technical Requirements for the Reg-
istration of Pharmaceuticals for Human Use]–Good Clinical Prac-
tice (ICH/GCP) criteria, including independent regular monitoring
and establishment of an independent data safety monitoring com-
mittee. All study participants provided written informed con-
sent and the study was approved by local ethics committees.
Patients were randomized to receive verum acupuncture, sham
acupuncture, or guideline-based conventional therapy. All in-
terventions comprised ten 30-minute sessions, generally 2 ses-
sions per week, and 5 additional sessions if, after the tenth ses-
sion (
Figure 2), patients experienced a 10% to 50% reduction
in pain intensity (Von Korff Chronic Pain Grade Scale).
terviewers and patients were blinded to this criterion. In all tele-
phone interviews, patients were asked specifically about use
of medication and physical therapy.
The sterile, disposable needles (Asiamed, Pullach near Mu-
nich, Germany) used for verum and sham acupuncture were
identical and were either 0.25 40 mm or 0.35 50 mm. Only
body needle acupuncture, without electrical stimulation or moxi-
bustion, was allowed. Verum acupuncture consisted of nee-
dling fixed points and additional points (from a prescribed list)
chosen individually on the basis of traditional Chinese medi-
cine diagnosis, including tongue diagnosis. Fourteen to 20
needles were inserted to a depth of 5 to 40 mm depending on
location. Induction of de Qi (the sensation felt when an acu-
puncturist reaches the level of Qi [numb radiating sensation
indicative of effective needling] in the body) was elicited by
manual stimulation. Sham acupuncture on either side of the
lateral part of the back and on the lower limbs was also stan-
dardized, avoiding all known verum points or meridians. As
with verum acupuncture, 14 to 20 needles were inserted, but
superficially (1-3 mm) and without stimulation.
The methods of acupuncture and Chinese diagnosis were es-
tablished on the basis of the international literature and a con-
sensus process with international experts. The exact method of
acupuncture has been published.
For acute episodes of pain,
only rescue medication was permitted in both acupuncture
groups. This was strictly defined as nonsteroidal anti-
inflammatory drugs to be taken on no more than 2 days per week
up to the maximum daily dose during the therapy period and
only 1 day per week during follow-up. Use of any additional thera-
pies for pain during the entire study period was prohibited
Patients in the conventional therapy group received a mul-
timodal treatment program according to German guidelines.
The guidelines provide the treating physician with recommen-
dations about the treatment algorithm and assess the various
therapy forms according to the degree of evidence based on a
literature search and recommendations of the specialist asso-
ciations. Conventional therapy included 10 sessions with per-
sonal contact with a physician or physiotherapist who admin-
istered physiotherapy, exercise, and such.
Table 1. Eligibility Criteria
Inclusion Criteria
Signed written informed consent
Clinical diagnosis of chronic low back pain for 6 mo or longer
CPGS grade I and HFAQ less than 70%
Therapy-free interval7dorlonger
Older than 18 y
Ability to speak, read, and write German
Exclusion criteria
Treatment with needle acupuncture for low back pain at any time in
the past
Treatment with needle acupuncture for any other indication within
the last year
History of spinal fracture (eg, osteoporosis or trauma) or disc or
spinal surgery
Infections or tumors of the spine
Systemic bone or joint disorders (eg, rheumatoid arthritis)
Scoliosis or kyphosis
Sciatica or chronic pain from other disease
Hemorrhagic disorders or anticoagulant therapy
Skin disease in the area of acupuncture
Abuse of drugs or pain medication
Patient included in any other studies
Abbreviations: CPGS, Von Korff Chronic Pain Grade Scale; HFAQ, Hanover
Functional Ability Questionnaire.
Allocated to verum
Allocated to sham
Allocated to sham
Excluded for
Participants assessed
for eligibility
Participants were
at 6-wk Assessment370
Missed assessment17
at 6-wk Assessment375
Missed assessment12
at 6-wk Assessment361
Missed assessment26
at 3-mo Assessment373
Missed assessment14
at 3-mo Assessment376
Missed assessment11
at 3-mo Assessment361
Missed assessment26
at 6-mo Assessment376
Missed assessment11
at 6-mo Assessment364
Missed assessment25
at 6-mo Assessment377
Missed assessment10
Participants were excluded640
Insufficient severity (HFAQ)342
Met exclusion criteria233
Withdrew informed consent44
For other reasons21
Figure 1. Participant flowsheet. HFAQ indicates Hanover Functional Ability
Questionnaire; ITT, intention to treat.
©2007 American Medical Association. All rights reserved.
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Physiotherapies were supported by nonsteroidal anti-
inflammatory drugs or pain medication up to the maximum
daily dose during the therapy period. Rescue medication was
identical to that for the acupuncture groups.
During acupuncture treatment, communication with the pa-
tient was limited to necessary explanations to avoid unblind-
ing the patient by suggestive remarks. Patients in all 3 groups
were informed before randomization that acupuncture would
be offered after completion of the trial.
Telephone interviews by trained employees of the study center
were conducted at baseline and at 1
, 3, and 6 months. Our pri-
mary outcome was treatment response 6 months after random-
ization, defined as 33% improvement or better on 3 pain-related
items on the Von Korff Chronic Pain Grade Scale
or 12% improve-
ment or better on back-specific functional status measured by the
Hanover Functional Ability Questionnaire.
Patients who had re-
course to additional treatments other than rescue medication were
classified as nonresponders, as were unblinded patients.
Secondary outcomes were responder rate at 1
and 3 months
after randomization, scores on the 12-item Short Form Health
and patient global assessment of therapy effectiveness
on a scale of 1 (very good) to 6 (fail).
Physicians documented
medication use, acupuncture treatment, and adverse events at
each session and at the final examination after 6 months. Pa-
tient blinding was assessed at the 6-month interview by asking
whether their physician had informed them of their allocation
and, if not, by asking the method of acupuncture and how cer-
tain they were of their response.
All interview questions were
given to the patients during the baseline visit.
The 1:1:1 randomization was performed dynamically by a com-
puter program balancing for 2 levels of chronification (2or
2 years), 2 levels of fear avoidance belief
(4or4 average
total points), 2 levels of activity (60 or 60 minutes), patient
and trial center. The previous allocation scheme
and a prespecified list of random numbers were used. After suc-
cessful completion of the baseline interview and once the pa-
tient had come for the first treatment, the physician called a ran-
domization hotline that registered the patient in the study and
faxed the patient’s assigned treatment group to the physician.
Patients were blinded to the type of acupuncture. They were
told they would be treated with a traditional Chinese form of
acupuncture (verum), with a form of acupuncture developed
especially for this study (sham), or with conventional therapy.
Investigators could not be blinded to the method of acupunc-
ture, but the interviewers were.
The primary analysis included all randomized patients on the
intent-to-treat basis. Patients in all groups who missed the
6-month-assessment were, therefore, classified as nonre-
sponders. Response rates were tested for differences using the
2-sided Fisher exact test. The multiple testing problem caused
by the comparison of 3 treatment methods was handled by a
closed test procedure to guarantee the type I error level of 5%
for all pairwise comparisons. Two tests comparing verum acu-
puncture with the 2 control groups at a level of 2.5% each were
performed as a first step.
If this global test ruled out the null
hypothesis of no difference among the 3 treatments, then all 3
pairwise comparisons were performed at a level of 5%. The study
was powered to detect a change of 10% in response rates (verum
acupuncture, 60%; conventional therapy, 50%; and sham acu-
puncture, 40%), with 95% power for the global test. Assum-
ing a 30% dropout rate, this led to a required sample size of
354 patients per group. Exploratory analyses were performed
for all secondary end points. Sensitivity analyses included com-
parisons with grouping by treatment, dropping patients who
missed the 6-month assessment, and best and worst imputa-
tion of missing data at 6-month assessment in all pairwise com-
Overall, 1802 patients with low back pain were screened,
and 1162 were randomized between March 7, 2002 (first
randomization), and December 12, 2004 (last random-
ization) (Figure 1). The primary reason for nonrandom-
ization was insufficient severity of disability as mea-
sured with the Hanover Functional Ability Questionnaire.
One patient dropped out because of pregnancy and was
excluded from the primary analysis. Twenty-three pa-
tients in the intent-to-treat population in the conven-
tional therapy group missed the 6-month telephone as-
sessment and were, thus, classified as nonresponders. They
Rechecking of
eligibility criteria
Primary outcome
Treatment extension
(5 sessions)
Primary contact
Patient consent for participation
Physician checks eligibility criteria
Patient receives questionnaires;
physician reports patient to central
data center using a fax
–17 d
Baseline interview
plus primary
outcome measure
–3 d
Baseline Phase
Telephone interviews
Physician receives
result of randomization
from data center
Start of treatment
90 d 180 d
42 d
14 Days before baseline interview
Treatment Phase
10 Sessions
Figure 2. Study design for German Acupuncture Trial for Chronic Lower Back Pain. Adapted from Endres et al.
©2007 American Medical Association. All rights reserved.
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were not included in a secondary sensitivity analysis,
thereby statistically favoring the conventional therapy.
This reduced the therapy effect in the response rates be-
tween acupuncture and conventional therapy by less than
1%. Overall, the primary results remain stable. Balanced
randomization ensured that there were no relevant dif-
ferences between the 3 treatment groups insofar as the
5 potentially prognostic factors (
Table 2).
A total of 13 475 treatment sessions were conducted
(verum acupuncture, 4821 [mean, 12.5 per patient]; sham
acupuncture, 4590 [mean, 11.9 per patient]; conven-
tional therapy, 4064 [mean, 10.5 per patient]). Mean±SD
treatment time per session was 30.5±2.5 minutes in all
groups. The number of patients who received the 5 ad-
ditional sessions was 232 (59.9%) in the verum group,
209 (54.3%) in the sham group, and 192 (52.5%) in the
conventional group. The therapies given in the conven-
tional group were physiotherapy (n=197; mean, 11.7 ses-
sions per patient), massage (n=180; mean, 9.5 sessions
per patient), heat therapy (n=157; mean, 9.7 sessions per
patient), electrotherapy (n= 65; mean, 8.8 sessions per
patient), back school (ie, a practical education in the man-
agement of back pain) (n=36; mean, 8.1 sessions per pa-
tient), injections (n= 48; mean, 5.6 per patient), and guid-
ance (n =56; mean, 4.2 sessions per patient). In a few
patients, therapies included infusions, yoga, hydrojet treat-
ment, and swimming. Pharmacologic treatment in the
conventional therapy group consisted of analgesics in 95%
of patients (n=183; mean, 16.2 per patient). At the end
of the study, patients rated the credibility of both acu-
puncture forms positively. Blinding seems to have been
maintained: most patients did not correctly identify or
did not know which form they had received (
Table 3).
Primary outcome at 6 months could be assessed in 96.1%
(1117 patients [377 received verum; 376 sham, and 364
standard treatment]) of all randomized patients.
Table 4 gives the response rates and between-group dif-
ferences at 6 months. Almost half of patients in the acu-
puncture groups but only one-fourth of patients in the
conventional therapy group benefited. Because the P value
of the comparison of verum acupuncture and conven-
tional therapy is 2.5% and the P value of the compari-
son of sham acupuncture and conventional therapy is
5.0%, both differences are statistically significant ac-
cording to the closed testing procedure.
Verum acupuncture was not superior to sham acupunc-
ture, with an observed difference of 3.4% (P=.39). Before
application of the nonresponder criterion, success rates were
about 30% greater; that is, in any group, about 25% of pa-
Table 2. Baseline Characteristics in 1162 Patients Randomized and 640 Patients Screened-Only
Baseline Characteristic
Verum Acupuncture
(n = 387)
Sham Acupuncture
(n = 387)
Standard Therapy
(n = 388)
Screened Only
(n = 640)
Sex, No.(%)
Men 165 (42.6) 140 (36.2) 165 (42.5) 267 (41.7)
Women 222 (57.4) 247 (63.8) 223 (57.5) 373 (58.3)
Age, y 49.6 ± 14.6 (380) 49.2 ± 14.8 (382) 51.3 ± 14.5 (381) 48.5 ± 14.7 (619)
Body mass index
26.9 ± 4.7 (381) 26.5 ± 4.8 (378) 26.3 ± 4.5 (378) 26.1 ± 4.4 (614)
Prognostic factors
History of back pain, y 8.1 ± 7.7 (380) 7.7 ± 8.2 (382) 8.1 ± 8.3 (380) 7.6 ± 7.6 (617)
Patient expectations
7.6 ± 1.7 (387) 7.7 ± 1.8 (387) 7.7 ± 1.8 (388) 7.4 ± 1.9 (512)
Fear avoidance beliefs
3.3 ± 1.3 (387) 3.2 ± 1.3 (387) 3.3 ± 1.3 (388) 3.6 ± 1.2 (54)
Physical activity,
min/d 70.5 ± 121.5 (377) 67.1 ± 119.3 (347) 67.5 ± 117.4 (381) 48.8 ± 106.9 (54)
Pain, CPGS 67.7 ± 13.9 67.8 ± 13.2 67.8 ± 14.6 NA
Disability, HFAQ 46.3 ± 14.7 46.3 ± 15.3 46.7 ± 14.5 NA
Quality of life, SF-12 NA
Physical component summary 31.8 ± 6.8 31.5 ± 6.9 31.6 ± 6.8
Mental component summary 46.6 ± 12.3 46.6 ± 11.5 47.1 ± 11.6
Abbreviations: GCPS, Von Korff Chronic Pain Grade Scale (low values better); HFAQ, Hanover Functional Ability Questionnaire (high values better); NA, not
available; SF-12, 12-item Short-Form Health Survey (high values better).
Data are given as mean ± SD (number of patients) unless otherwise indicated.
Calculated as weight in kilograms divided by height in meters squared.
Not at all helpful, 0; extremely helpful, 10.
Beliefs about back pain caused by physical activity: not at all, 0; absolutely true, 6.
Table 3. Assessment of Patient Blinding at End of Study
Type of
Type of
Patients Stated
They Had
Level of Confidence
of Patient Answers
TotalCertain Uncertain
Specific 45 (42.5) 61 (57.5) 106 (28.1)
Nonspecific 48 (44.0) 61 (56.0) 109 (28.9)
Don’t know 126 (33.4)
Missing 36 (9.5)
Specific 26 (30.2) 60 (69.8) 86 (22.9)
Nonspecific 49 (39.5) 75 (60.5) 124 (33.0)
Don’t know 141 (37.5)
Missing 25 (6.6)
Data are given as number (percentage).
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tients were classified as nonresponders because they had re-
course to additional therapies (
Table 5). Patients in both
acupuncture groups also had clinically meaningful better
results for all secondary outcome measures, including medi-
cation use (
Table 6). No center effects were found.
During the 6 months after randomization, 40 serious ad-
verse events were documented, 12 each in the verum and
sham acupuncture groups and 16 in the conventional
therapy group. All were deemed unrelated to the inter-
vention. The number of serious adverse events corre-
sponds to the statistically expected frequency.
In ad-
dition, 476 clinically relevant adverse effects were reported
by 257 patients (22.6%), with no significant difference
between therapy groups (P= .81).
To our knowledge, the present study is the largest and most
rigorous trial to investigate the efficacy of verum acupunc-
ture for chronic low-back pain compared with sham acu-
puncture and guideline-based conventional therapy. The
study yielded several surprising results. First, almost half of
the patients in both acupuncture groups were responders.
They experienced clinically relevant improvement in pain
intensity or back-specific disability without having recourse
to concomitant therapies. Second, only one-fourth of the pa-
tients receiving conventional therapy, consisting of a mul-
timodal combination of pharmacologic and nonpharmaco-
logic treatments, responded to treatment. Acupuncture, re-
gardless of the technique, was significantly more effective
than conventional therapy at all follow-up points. To our
knowledge, this is the first time superiority of acupuncture
over conventional treatment has been unequivocally dem-
onstrated for the primary and secondary outcomes, includ-
ing medication reduction, in contrast to studies with a usual-
care group.
Third, there was essentially no difference be-
tween the results for verum and sham acupuncture.
What conclusions can be drawn from these findings?
First, the unexpected finding of similar effectiveness of
sham and verum acupuncture forces us to question the
underlying action mechanism of acupuncture and to ask
whether the emphasis placed on learning the traditional
Chinese acupuncture points may be superfluous. Sec-
ond, while all randomized trials and meta-analyses to date
have failed to show a clear advantage of acupuncture over
conventional therapy for chronic low back pain, our find-
ings demonstrate significant superiority.
A recently published meta-analysis of acupuncture for
low back pain
concluded that “Current preliminary data
suggest that acupuncture may be more effective than inef-
fective controls for providing short-term relief of chronic low-
back pain.”
In contrast, we show superiority over an
active control group. The nonsuperiority of verum over sham
acupuncture found in our study is in agreement with a re-
cently published study
that was conducted at the same time
as ours.
The comparison of sham vs verum acupuncture was in-
tended to differentiate the physiologic (specific) from the
psychologic (nonspecific) effects of acupuncture. Among
the nonspecific effects for both forms of acupuncture are
positive patient expectations about acupuncture paired with
negative expectations about conventional medicine, more
intensive physician contact, and the experience of an in-
vasive technique (needling). Given that the 2 forms of acu-
puncture are indistinguishable to the patient, any differences
in outcomes between the 2 forms must be attributable to
specific treatment effects. However, the 2 forms did not dif-
Table 5. Treatment Response After 6 Months
Treatment Response
132 (34.1) 197 (50.9) 229 (59.2)
195 (50.4) 251 (64.9) 281 (72.6)
Combined CPGS and HFAQ
223 (57.6) 277 (71.6) 304 (78.5)
Total No. of patients 387 387 387
Combined GCPS, HFAQ,
and unblinded patients
164 (42.4) 125 (32.3 112 (28.9)
Responders 223 (57.6) 262 (67.7) 275 (71.1)
Overall treatment response
including proscribed
rescue medication
281 (72.6) 216 (55.8) 203 (52.4)
Responders 106 (27.4) 171 (44.2) 184 (47.6)
Total No. of Patients 387 387 387
Abbreviations: CPGS, Von Korff Chronic Pain Grade Scale; HFAQ, Hanover
Functional Ability Questionnaire for measuring back pain–related functional
Values are given as number of patients (percentage).
Success was defined as 33% improvement or better on 3 pain-related items
on the GCPS.
Success was defined as 12% improvement or better on the back-specific
Success was defined as 33% improvement or better on 3 pain-related items
on the CPGS or as 12% improvement or better on the back-specific HFAQ.
Patients who had no success in the combined CPGS, HFAQ, or unblinded
Patients who had no success in the combined CPGS, HFAQ, or unblinded
groups; missed the 6-month assessment; or had recourse to other than
permitted concomitant therapies during follow-up, regardless of symptom
Table 4. Primary Outcome: Pairwise Comparison
of Treatment Response 6 Months After Randomization
Treatment Response Intergroup Difference P Value
Group 1 vs group 3
47.6 (42.4 to 52.6) vs
27.4 (23.0 to 32.1)
20.2 (13.4 to 26.7) .001
Group 2 vs group 3
44.2 (39.2 to 49.3) vs
27.4 (23.0 to 32.1)
16.8 (10.1 to 23.4) .001
Group 1 vs group 2
47.6 (42.4 to 52.6) vs
44.2 (39.2 to 49.3)
3.4 (−3.7 to 10.3) .39
Each group comprised 387 patients. Values are given as percentage of
patients (95% confidence interval). Group 1, verum acupuncture; group 2,
sham acupuncture; group 3, conventional therapy.
Unadjusted; Fisher exact test (intention-to-treat analysis).
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fer insofar as the primary outcome. This cannot be explained
solely by positing the existence of additional, previously un-
known acupuncture points or regions because in the sham
acupuncture, needles were inserted only very shallowly and
without elicitation of de Qi. Several other hypotheses must
be considered instead: (1) there are no specific acupunc-
ture effects at all; (2) the specific acupuncture effect is very
small and is overlaid by nonspecific effects; and (3) there
exist specific acupuncture effects, the nature of which is still
unknown, that lead to symptom improvement independent
of point selection and depth of needling.
The results for conventional therapy were significantly
poorer than those in the 2 acupuncture groups. This raises
questions about qualitative and quantitative aspects of con-
ventional therapy. The number and duration of patient-
therapist contacts were designed to be as similar as pos-
sible to those in the acupuncture groups. A comparison of
the conventional therapy as delivered in our study with sev-
eral studies of routine care in Germany (eg, Chenot et al
shows that the treatment in this study was superior in both
quality and quantity. We, therefore, assume an efficient level
of care for the conventional therapy arm.
To minimize potential nocebo effects, participants had
the opportunity to receive 10 acupuncture sessions af-
ter the completion of the study regardless of their as-
signed group. Furthermore, every patient had the alter-
native of participating in a cohort study designed to
examine the adverse effects of acupuncture therapy.
advantage of this was that patients with positive expec-
tations of acupuncture and negative expectations of con-
ventional therapy could be excluded at the outset.
The superiority of both forms of acupuncture sug-
gests a common underlying mechanism that may act on
pain generation, transmission of pain signals, or process-
ing of pain signals by the central nervous system and that
is stronger than the action mechanism of conventional
therapy. The underlying mechanism may be a kind of su-
perplacebo effect produced by placebo and all nonspe-
cific factors working together. Nevertheless, the effec-
tiveness of acupuncture cannot be attributed merely to
a placebo effect because there is no reason to believe that
the action mechanism of conventional therapy is the re-
sult solely of the placebo effect. Nor can the conditions
of a randomized trial be responsible for the unexpected
success because the same success rates after 3 and 6
months were measured under conditions of everyday prac-
Nevertheless, the effectiveness of sham acupunc-
ture and the principle of nihil nocere suggest that a dis-
cussion is called for about the necessary depth of insertion
of acupuncture needles.
Table 6. Results for Secondary End Points in 3 Therapy Groups
Secondary End Point Verum Acupuncture Sham Acupuncture Conventional Therapy
Treatment response
60.7 (387) 59.2 (387) 56.1 (387)
55.0 (387) 51.9 (387) 41.9 (387)
Disability, HFAQ
Baseline 46.3 ± 14.7 (387) 46.3 ± 15.3 (387) 46.7 ± 14.5 (387)
6 wk 64.0 ± 21.1 (370) 61.3 ± 20.8 (375) 56.3 ± 20.8 (361)
3 mo 65.4 ± 22.9 (373) 61.3 ± 22.7 (376) 56.0 ± 22.0 (361)
6 mo 66.8 ± 23.1 (377) 62.2 ± 23.0 (376) 55.7 ± 22.7 (364)
Pain, CPGS
Baseline 67.7 ± 13.9 (387) 67.8 ± 13.2 (387) 67.8 ± 14.6 (387)
6 wk 48.6 ± 18.5 (370) 51.0 ± 18.7 (375) 57.1 ± 16.5 (361)
3 mo 45.4 ± 19.4 (373) 48.5 ± 19.5 (376) 54.8 ± 18.4 (361)
6 mo 40.2 ± 22.5 (377) 43.3 ± 23.0 (376) 52.3 ± 21.2 (364)
Quality of life, SF-12 physical score
Baseline 31.8 ± 6.8 (385) 31.5 ± 6.9 (386) 31.6 ± 6.8 (384)
3 mo 40.3 ± 10.1 (370) 39.2 ± 9.7 (372) 36.1 ± 8.9 (361)
6 mo 41.6 ± 10.5 (373) 39.5 ± 10.1 (372) 35.8 ± 9.5 (364)
Quality of life, SF-12 mental score
Baseline 46.6 ± 12.3 (385) 46.6 ± 11.5 (386) 47.1 ± 11.6 (384)
3 mo 50.5 ± 11.1 (370) 50.2 ± 11.0 (372) 48.6 ± 11.6 (361)
6 mo 50.7 ± 11.1 (373) 50.9 ± 10.8 (372) 49.2 ± 11.8 (364)
Patient global assessment
6 wk 2.8 ± 1.2 (369) 3.1 ± 1.4 (375) 3.5 ± 1.3 (360)
3 mo 2.8 ± 1.3 (371) 3.1 ± 1.4 (376) 3.6 ± 1.3 (359)
6 mo 2.8 ± 1.3 (376) 3.0 ± 1.4 (375) 3.5 ± 1.3 (362)
Study cessation, No. (%) 34 (8.8) 39 (10.1) 50 (12.9)
Abbreviations: CPGS, Von Korff Chronic Pain Grade Scale; HFAQ, Hanover Functional Ability Questionnaire; SF-12, 12-item Short-Form Health Survey.
Treatment response after 6 weeks was defined as 33% improvement or better on 3 pain-related items on the CPGS or 12% improvement or better on the
back-specific HFAQ. Patients in the acupuncture groups who had recourse to other than permitted concomitant therapies during the study were classified as
nonresponders regardless of symptom improvement.
Treatment response after 3 months was defined as 33% improvement or better on 3 pain-related items on the CPGS or 12% improvement or better on the
back-specific HFAQ. Patients who had recourse to other than permitted concomitant therapies during the therapy and follow-up up to 3 months were classified as
nonresponders regardless of symptom improvement.
Low values better.
High values better.
©2007 American Medical Association. All rights reserved.
at University College London, on September 25, 2007 www.archinternmed.comDownloaded from
The strengths of our study include an active multimo-
dal conventional therapy control group, high-power, regu-
lar monitoring, assessment of blinding maintenance, struc-
tured telephone interviews, a clinically relevant primary
outcome, and a low dropout rate. Potential limitations of
the study were restricting acupuncture to needling only,
restricting the number of sessions to 10 to 15, and inabil-
ity to blind acupuncturists to the form of acupuncture. How-
ever, we believe that nonblinding of acupuncturists did not
lead to major bias because patient blinding to type of acu-
puncture was maintained even for 6 months.
Acupuncture constitutes a strong therapy alternative
to multimodal conventional therapy. Acupuncture gives
physicians a promising and effective treatment option for
chronic low back pain, with few adverse effects or con-
traindications. The improvements in all primary and
secondary outcome measures were significant and lasted
long after completion of treatment. Because they di-
rectly compared acupuncture and conventional therapy,
the GERAC trials were the decisive trials on which the
German Federal Joint Committee of Physicians and Health
Insurance Plans, a body similar to the National Institute
for Health and Clinical Excellence in the United King-
dom or the National Institutes of Health in the United
States, based its decision to make acupuncture for chronic
low back pain an insured benefit, for the first time put-
ting acupuncture on an equal footing with conventional
Accepted for Publication: May 20, 2007.
Correspondence: Heinz G. Endres, MD, Department of
Medical Informatics, Statistics and Epidemiology, Ruhr-
Universita¨t Bochum, Universitaetsstrasse 150, D-44801
Bochum, Germany (heinz.endres@ruhr-uni-bochum
Author Contributions: Dr Mu¨ ller and Ms Schade-Brittinger
had full access to all of the data in the study and take respon-
sibility for the integrity of the data and the accuracy of the
data analysis. Study concept and design: Haake, Mu¨ ller, Schade-
Brittinger, Basler, Scha¨fer, Maier, Endres, Trampisch, and
Molsberger. Acquisition of data: Schade-Brittinger and Ma-
ier. Analysis and interpretation of data: Haake, Mu¨ ller, Schade-
Brittinger, Endres, and Molsberger. Drafting of the manuscript:
Haake, Mu¨ ller, Schade-Brittinger, Basler, Scha¨fer,Maier, En-
dres, Trampisch, and Molsberger. Critical revision of the manu-
script for important intellectual content: Haake, Mu¨ ller, Schade-
Brittinger, Basler, Scha¨fer, Maier, Endres, and Molsberger.
Statistical analysis: Mu¨ ller, Scha¨fer, and Trampisch. Obtained
funding: Scha¨fer. Administrative, technical, and material sup-
port: Schade-Brittinger, Basler, Maier, and Molsberger. Study
supervision: Molsberger.
Financial Disclosure: None reported.
Funding/Support: This study was supported by the follow-
ing German public health insurance companies: Allgeme-
ine Ortskrankenkasse, Betriebskrankenkasse, Innungskran-
kenkasse, Bundesknappschaft, Bundesverband der Land-
wirtschaftlichen Krankenkassen, and Seekasse.
Role of the Sponsors: The funders had no role in the de-
sign and conduct of the study; data collection, manage-
ment, analysis, and interpretation of the data; or prepa-
ration, review, or approval of the manuscript.
Additional Contributions: We thank the patients and col-
leagues in the participating centers involved in this project
and the members of the independent data and safety moni-
toring committee for their recommendations. The staff
of Winicker Norimed (Nuremberg) and the Coordina-
tion Centers for Clinical Trials of the Universities of
Du¨ sseldorf, Heidelberg, Mainz, and Marburg contrib-
uted to monitoring and study management (http://www
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... Fourteen randomized trials were finally included. [34][35][36][37][38][39][40][41][42][43][44][45][46][47] We grouped the included studies in two main groups: 1) acupuncture alone: studies comparing acupuncture to conventional therapy (pharmacotherapy, non-pharmacologic treatments, combination of pharmacologic and non-pharmacologic treatments); 2) acupuncture as add-on to conventional treatment: studies comparing acupuncture in addition to conventional therapy to conventional therapy alone. Ten studies assessed the efficacy and safety of acupuncture alone and six assessed the efficacy of acupuncture as add-on to conventional therapy ( Fig. 1 ). ...
... Two studies 38 , 47 provided data for both the comparisons. The trials included a total 2440 participants; mean age ranged from 33 to 81 years, two studies did not report this information; mean percentage of female (ranged from 23% to 90%), three studies did not report this information; mean percentage of participants with chronic pain for at least one year ranged from 61% to 75% in five studies; four studies reported a mean duration of back pain of 8.1 (SD 8), 37 6.9 (SD NR), 47 9.6, 43 9.9 44 years respectively and one of 22 months, 40 four studies did not report this information. 36 , 38 , 39 , 46 Mean duration of treatments ranged from 3 to 12 weeks Three studies were conducted in US, three in Germany and one each in Japan, Taiwan, India, Hong Kong, Lebanon, China, Iran and UK. ...
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Background: Conventional therapies (CTs), pharmacological (PH) and non-pharmacological (NPH), do not always achieve benefits in the treatment of chronic low back pain (CLBP). We assessed efficacy and safety of acupuncture for CLBP as alternative or addition to CT. Methods: We included randomised controlled trials (RCTs) comparing acupuncture alone or in combination with CT to CT. We searched Medline, Cochrane Library, Embase up to May 2022. We assessed risk of bias with the original Cochrane tool and GRADE certainty of evidence. Results were pooled through meta-analysis. Results: Ten RCTs (2122 participants) were included comparing acupuncture versus CT and 6 (374 participants) comparing acupuncture plus CT to CT alone. Comparing acupuncture with NPH or PH, no differences were found for pain and disability. Comparing with combined PH and NPH, pain and disability were reduced (SMD=-0.50, 95%CI-0.62 to -0.37; SMD=-0.71, 95%CI-1.17 to -0.24). Comparing acupuncture plus NPH with NPH alone, pain and disability were reduced (SMD=-0.70, 95%CI-0.94 to -0.46; SMD=-0.95, 95%CI-1.36 to -0.54). Comparing acupuncture plus PH with PH alone, pain and disability were reduced (MD=-0.21,8 95%CI-433.28 to -10.42; MD=-3.1, 95%CI-4.87 to -1.83). Comparing acupuncture plus combined treatment versus combined treatment alone, no differences were found in pain, while disability was reduced (MD=-3.40 95%CI-5.17 to -1.63). No studies assessed adverse event. Certainty of evidence ranged from moderate to very low. Conclusion: We are uncertain whether acupuncture is more effective and safer than CT. In the comparisons without estimates' imprecision, acupuncture showed promising results. Acupuncture could be an option based on patients' preferences.
... Owing to the pilot design with heterogeneity of patients, surgeries, and intervention time points, the trial was neither randomized nor blinded and prone to selection, performance, and detection bias. Thus, a placebo effect with similar pain reduction effects cannot be eliminated [41]. However, data of the current study can be used for a sample size calculation for future randomized, blinded trials to validate the effect of checkpoint acupuncture after abdominal surgery. ...
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Background Optimal pain management is one of the core elements of Enhanced Recovery After Surgery (ERAS®) protocols and remains a challenge. Acupuncture (AC) is an effective treatment for various pain conditions. Systematic and personalized allocation of acupoints may be decisive for efficacy. Methods Based on the predominant pressure sensitivity of six gastrointestinal (GI) checkpoints (G1-G6), we devised a method to detect personalized patterns of pain and a corresponding set of acupoints. We performed a single AC treatment with semi-permanent needles and assessed the visual analogue scale (VAS) score, pain threshold based on pressure algometry (PA) and temperature changes on abdominal skin areas before and 5 min after AC. Results Between April and June 2021, thirty-eight patients were prospectively included in this pilot study. The mean reduction in subjective pain sensation as assessed by VAS was 86%, paralleled by an augmentation of the pain threshold as measured by PA by 64%. A small but significant increase in the skin temperature was observed above the abdominal surface. These effects were independent of the type of surgery. Conclusion Checkpoint acupuncture may be a complementary tool for postoperative pain management. Further investigations are needed to explore this analgesic effect.
... Acupuncture as a therapeutic modality has been accepted by modern clinical medicine and used to treat a variety of diseases, such as chronic pain management, osteoarthritis, migraine, anxiety, hot flashes in postmenopausal women, chronic fatigue, neuropathy, nausea, vomiting, xerostomia, and dysphagia. [135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150][151] Several clinical trials have proven that acupuncture can enhance a patient's overall QoL by mitigating extremity swelling and lymphedema symptoms. [152][153][154] A study at the Memorial Sloan-Kettering Cancer Center (MSKCC) has reported that acupuncture therapy as an adjunct therapy can decrease the overall volume of extremities during lymphedema and minimize the infection rate or other severe side effects. ...
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Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.
Importance: When sham acupuncture is set as a control in evaluating acupuncture, the sham needling technique is usually different from acupuncture. However, the sham procedure is conducted either at the same points that are used for the acupuncture group or at nonindicated points. Objective: To assess whether the outcome of sham acupuncture varies according to the needling points in sham-controlled trials of acupuncture for chronic nonspecific low back pain (CLBP) as an example. Data sources: Searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Allied and Complementary Medicine Database were conducted on February 12, 2023. Study selection: Randomized clinical trials (RCTs) assessing the outcomes of acupuncture in sham acupuncture-controlled or waiting list-controlled trials on CLBP were included. Data extraction and synthesis: Two researchers independently extracted data on study characteristics and outcomes and assessed quality. Sham acupuncture was classified according to whether it was conducted at the same acupuncture points used in the acupuncture group, referred to as sham acupuncture therapy (verum) (SATV) or at different points, referred to as sham acupuncture therapy (sham) (SATS). Clinical similarity, transitivity, and consistency tests were conducted, followed by a random-effects frequentist network meta-analysis (NMA). Main outcomes and measures: The primary outcome was pain, and the secondary outcome was back-specific function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMD) with 95% CIs. The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for findings was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Ten RCTs involving 4379 participants were included. In comparison with SATS, acupuncture was significantly associated with improvements in both pain (SMD, -0.33; 95% CI, -0.52 to -0.15) and function outcomes (SMD, -0.13; 95% CI, -0.25 to -0.02); however, there were no differences between acupuncture and SATV. In comparison with SATS, SATV was significantly associated with better pain (SMD, -0.45; 95% CI, -0.88 to -0.03) and function outcomes (SMD, -0.30; 95% CI, -0.56 to -0.05). The risk of bias that could affect the interpretation of the results was usually low, and the certainty of evidence was moderate to low. Conclusions and relevance: In this NMA, sham acupuncture needling at the same points as those in acupuncture was not a true placebo control for assessing the efficacy of acupuncture for CLBP and might underestimate the outcome of acupuncture in clinical settings.
Background: Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect. Objective: To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses. Methods: Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size. Results: A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response. Conclusions: Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).
Background: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. Objective: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. Search strategy: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. Inclusion criteria: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. Data extraction and analysis: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. Results: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. Conclusion: Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: a meta-analysis. J Integr Med. 2023; Epub ahead of print.
Objective: To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU). Methods: A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Results: A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant. Conclusions: Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).
Expectations can profoundly modulate pain experience, during which the periaqueductal gray (PAG) plays a pivotal role. In this article, we focus on motivationally evoked neural activations in cortical and brainstem regions both before and during stimulus administration, as has been demonstrated by experimental studies on pain-modulatory effects of expectations, in the hope of unraveling how the PAG is involved in descending and ascending nociceptive processes. This motivational perspective on expectancy effects on the perception of noxious stimuli sheds new light on psychological and neuronal substrates of pain and its modulation, thus having important research and clinical implications.
Objective: This pilot study explored interactions of domains of physical, psychologic, and social factors in the Patient-Reported Outcomes Measurement Information System® (PROMIS®)-29 system and their dynamic changes during acupuncture treatment of chronic musculoskeletal pain. Materials and methods: PROMIS-29 profile, version 2.1 was applied among participants with chronic musculoskeletal pain, who received acupuncture treatment for 5 weeks. Data from function-oriented and symptom-oriented domains as well as changes in pain intensity were evaluated at weeks 0, 3, and 5, in 9 patients who completed full sessions. Scores of the domains were analyzed by hierarchical cluster analysis at each timepoint to identify the patterns of interactions of PROMIS domains. Results: Hierarchical cluster analysis revealed the existence of 2 main clusters: one consisting of pain, fatigue, and emotional domains; the other comprising physical function and social domains. The general pattern was stable but interactions were found throughout the treatment. The score for sleep disturbance did not improve but was correlated with different domains at varying stages of treatment. Conclusions: Interaction between 2 clusters of pain with fatigue and emotional domains; and physical function with social domains showed that acupuncture produces holistic reductions in chronic musculoskeletal pain. However, the limitation of sample size and bias in this pilot study requires future research on the need to adopt an interdisciplinary and holistic approach to the recovery of patients with chronic musculoskeletal pain, who have dynamic needs.
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Data from general population surveys (n = 1483 to 9151) in nine European countries (Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) were analyzed to cross-validate the selection of questionnaire items for the SF-12 Health Survey and scoring algorithms for 12-item physical and mental component summary measures. In each country, multiple regression methods were used to select 12 SF-36 items that best reproduced the physical and mental health summary scores for the SF-36 Health Survey. Summary scores then were estimated with 12 items in three ways: using standard (U.S.-derived) SF-12 items and scoring algorithms; standard items and country-specific scoring; and country-specific sets of 12 items and scoring. Replication of the 36-item summary measures by the 12-item summary measures was then evaluated through comparison of mean scores and the strength of product-moment correlations. Product-moment correlations between SF-36 summary measures and SF-12 summary measures (standard and country-specific) were very high, ranging from 0.94-0.96 and 0.94-0.97 for the physical and mental summary measures, respectively. Mean 36-item summary measures and comparable 12-item summary measures were within 0.0 to 1.5 points (median = 0.5 points) in each country and were comparable across age groups. Because of the high degree of correspondence between summary physical and mental health measures estimated using the SF-12 and SF-36, it appears that the SF-12 will prove to be a practical alternative to the SF-36 in these countries, for purposes of large group comparisons in which the focus is on overall physical and mental health outcomes.
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We sought to investigate the potential of using a simple global estimation ('How effective do you think the treatment was?') as a measure of efficacy by comparing it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief) in acute pain studies. One hundred and fifty randomized, double-blind trials included in 11 systematic reviews of single dose, oral analgesics for postoperative pain were used as a source of data. The relationship between the proportion of patients reporting the top two or three values on a five-point global scale and the proportion with at least 50%maxTOTPAR was investigated. Twenty-six trials provided data on the proportion reporting the top two categories (very good or excellent) and 27 gave data on the top three categories (good, very good or excellent). The relationship between the percentage of patients recording the top two categories on a five-point global scale and the proportion with at least 50%maxTOTPAR was fair (r(2)=0.67). That for the top three categories was less good (r(2)=0.57). Similar numbers-needed-to-treat were calculated for aspirin 600/650 mg and ibuprofen 400 mg using at least 50%maxTOTPAR and the top two categories. No real difference was seen in the correlation for standard wording compared to non-standard wording. Individual patient data were also used from four randomized, placebo-controlled, double-blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was plotted for patients reporting each of the five categories on the global scale. A global assessment provides similar measures of analgesic efficacy as TOTPAR derived from hourly measurements, but the effects of adverse effects have yet to be understood.
Background: Low back pain limits activity and is the second most frequent reason for physicians visits. Previous research shows widespread use of acupuncture for low back pain. Purpose: To assess acupuncture's effectiveness for treating low back pain. Data Sources: Randomized, controlled trials were identified through searches of MEDLINE, Cochrane Central, EMBASE, AMED, CINAHL, CISCOM, and GERA databases through August 2004. Additional data sources included previous reviews and personal contacts with colleagues. Study Selection: Randomized, controlled trials comparing needle acupuncture with sham acupuncture, other sham treatments, no additional treatment, or another active treatment for patients with low back pain. Data Extraction: Data were dually extracted for the outcomes of pain, functional status, overall improvement, return to work, and analgesic consumption. In addition, study quality was assessed. Data Synthesis: The 33 randomized, controlled trials that met inclusion criteria were subgrouped according to acute or chronic pain, style of acupuncture, and type of control group used. For the primary outcome of short-term relief of chronic pain, the meta-analyses showed that acupuncture is significantly more effective than sham treatment (standardized mean difference, 0.54 [95% CI, 0.35 to 0.73]; 7 trials) and no additional treatment (standardized mean difference, 0.69 [CI, 0.40 to 0.98]; 8 trials). For patients with acute low back pain, data are sparse and inconclusive. Data are also insufficient for drawing conclusions about acupuncture's short-term effectiveness compared with most other therapies. Limitations: The quantity and quality of the included trials varied. Conclusions: Acupuncture effectively relieves chronic low back pain. No evidence suggests that acupuncture is more effective than other active therapies.
Many studies of acupuncture treatment are seriously flawed by methodological problems. Poor design, inadequate measures and statistical analysis, lack of follow-up data and sub-standard treatment are all too common. However, the major problem, which many investigators consider to be still unresolved, is the definition of an appropriate placebo control. The use of inappropriate placebo controls has bedeviled acupuncture research and led to serious misinterpretation of the results of clinical trials. While a number of different solutions have been proposed there is, as yet, no agreed way of assessing the adequacy of control conditions or of deciding which placebo to use in a particular trial. We propose that assessing the credibility of treatments and control conditions may provide a way forward to a more rigorous, consensus approach.
Pilot studies and a literature review suggested that fear-avoidance beliefs about physical activity and work might form specific cognitions intervening between low back pain and disability. A Fear-Avoidance Beliefs Questionnaire (FABQ) was developed, based on theories of fear and avoidance behaviour and focussed specifically on patients' beliefs about how physical activity and work affected their low back pain. Test-retest reproducibility in 26 patients was high. Principal-components analysis of the questionnaire in 210 patients identified 2 factors: fear-avoidance beliefs about work and fear-avoidance beliefs about physical activity with internal consistency (alpha) of 0.88 and 0.77 and accounting for 43.7% and 16.5% of the total variance, respectively. Regression analysis in 184 patients showed that fear-avoidance beliefs about work accounted for 23% of the variance of disability in activities of daily living and 26% of the variance of work loss, even after allowing for severity of pain; fear-avoidance beliefs about physical activity explained an additional 9% of the variance of disability. These results confirm the importance of fear-avoidance beliefs and demonstrate that specific fear-avoidance beliefs about work are strongly related to work loss due to low back pain. These findings are incorporated into a biopsychosocial model of the cognitive, affective and behavioural influences in low back pain and disability. It is recommended that fear-avoidance beliefs should be considered in the medical management of low back pain and disability.
This paper describes conceptual and clinimetric aspects as well as fields of application of the Hannover Functional Ability Questionnaire for measuring back pain-related disability (FFbH-R). The FFbH-R belongs to a series of short self-administered questionnaires for the assessment of functional limitations in activities of daily living among patients with musculoskeletal disorders. In addition to the FFbH-R, a specific version is available for patients with polyarticular diseases (the FFbH-P), as well as a combined version of both questionnaires. A new questionnaire for patients with osteoarthritis is currently being developed. Data from various studies indicate that the FFbH-R meets the relevant psychometric criteria of acceptability, reliability, validity, and sensitivity to change. It has been successfully applied in (observational and controlled) clinical studies, in epidemiologic surveys, and in compensation disability evaluation.
Although the literature is filled with information about the prevalence and incidence of back pain in general, there is less information about chronic back pain, partly because of a lack of agreement about definition. Chronic back pain is sometimes defined as back pain that lasts for longer than 7-12 weeks. Others define it as pain that lasts beyond the expected period of healing, and acknowledge that chronic pain may not have well-defined underlying pathological causes. Others classify frequently recurring back pain as chronic pain since it intermittently affects an individual over a long period. Most national insurance and industrial sources of data include only those individuals in whom symptoms result in loss of days at work or other disability. Thus, even less is known about the epidemiology of chronic low-back pain with no associated work disability or compensation. Chronic low-back pain has also become a diagnosis of convenience for many people who are actually disabled for socioeconomic, work-related, or psychological reasons. In fact, some people argue that chronic disability in back pain is primarily related to a psychosocial dysfunction. Because the validity and reliability of some of the existing data are uncertain, caution is needed in an assessment of the information on this type of pain.
The purpose of this study was to determine the levels of change on standard pain scales that represent clinically important differences to patients. Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious. Differences between groups, as summarized by a change in mean values over time, can be difficult to apply to clinical care. Baseline scores vary widely and group mean differences could reflect large changes in a few patients, small changes in many patients, or any combination of these outcomes. Determination of the proportion of patients who have a clinically important improvement in their pain would provide a more interpretable result with direct clinical implications. However, determining a clinically important outcome requires information about the degree of change over time that is clinically important. Data from the titration phase of a multiple cross-over randomized clinical trial of oral transmucosal fentanyl citrate (OTFC) for the treatment of cancer-related breakthrough pain were re-analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief. The scales evaluated were absolute pain intensity difference (PID, 0-10 scale), percentage pain intensity difference (PID%, 0-100% scale), pain relief (PR, 0 (none), 1 (slight), 2 (moderate), 3 (lots), 4 (complete)), sum of the pain intensity difference (SPID over 60 min), percentage of maximum total pain relief (% Max TOTPAR over 60 min), and global medication performance (0 (poor), 1 (fair), 2 (good), 3 (very good), 4 (excellent)). Adequate relief was defined by the patient's decision not to use another dose of opioid medication as a rescue, in addition to the study medication, to treat each painful episode. One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain. The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief, with balanced sensitivity and specificity. The best cut-off point for both the % Max TOTPAR and the PID% was 33%. The best cut-off points for the absolute scales were absolute pain intensity difference of 2, pain relief of 2 (moderate), and SPID of 2. The global medication performance of 2 (good) had excellent values as well. This study presents data-derived cut-off points for the changes in several pain scales, each reflecting the clinically important improvement for patients treating breakthrough cancer pain episodes with OTFC. Confirmation in other patient populations and different pain syndromes will be needed. The use of consistent clinically important cut-off points as the primary outcome in future pain therapy clinical trials will enhance their validity, comparability, and clinical applicability.