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

Abstract

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.

Full text

ORIGINAL INVESTIGATION
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
L
OW BACK PAIN IS A COMMON,
impairing, and disabling
condition, often long-term,
with an estimated lifetime
prevalence of 70% to 85%.
1
It is the second most common pain for
which physician treatment is sought and
a major reason for absenteeism and dis-
ability.
1,2
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.
2,3
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-
comes.
4
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.
5
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.
METHODS
STUDY DESIGN
AND PARTICIPANTS
The design of this multicenter, randomized trial
has been described.
6
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
score
7
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).
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tional Ability Questionnaire score of less than 70%,
8
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-
eases
6
(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.
INTERVENTIONS
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).
6
In-
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.
6,10
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.
11
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
Pregnancy
Epilepsy
Patient included in any other studies
Abbreviations: CPGS, Von Korff Chronic Pain Grade Scale; HFAQ, Hanover
Functional Ability Questionnaire.
Allocated to verum
acupuncture
387
ITT387
Allocated to sham
acupuncture
387
ITT387
Allocated to sham
acupuncture
388
Excluded for
pregnancy
1
ITT387
Participants assessed
for eligibility
1802
Participants were
randomized
1162
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.
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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.
OUTCOME MEASURES
Telephone interviews by trained employees of the study center
were conducted at baseline and at 1
1
⁄
2
, 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
7
or 12% improve-
ment or better on back-specific functional status measured by the
Hanover Functional Ability Questionnaire.
8
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
1
⁄
2
and 3 months
after randomization, scores on the 12-item Short Form Health
Survey,
12
and patient global assessment of therapy effectiveness
on a scale of 1 (very good) to 6 (fail).
13
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.
14
All interview questions were
given to the patients during the baseline visit.
RANDOMIZATION AND BLINDING
The 1:1:1 randomization was performed dynamically by a com-
puter program balancing for 2 levels of chronification (⬍2or
ⱖ2 years), 2 levels of fear avoidance belief
15
(⬍4orⱖ4 average
total points), 2 levels of activity (⬍60 or ⱖ60 minutes), patient
expectations,
16
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.
STATISTICAL ANALYSIS
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.
6
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-
parisons.
RESULTS
PARTICIPANTS
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
measure
Treatment extension
(5 sessions)
Primary contact
interview
Patient consent for participation
Physician checks eligibility criteria
Patient receives questionnaires;
physician reports patient to central
data center using a fax
–17 d
Screening
Baseline interview
plus primary
outcome measure
–3 d
Baseline Phase
Telephone interviews
Physician receives
result of randomization
from data center
Start of treatment
0
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.
9
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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).
TREATMENTS AND BLINDING
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.
CLINICAL OUTCOMES
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 ⱕ2.5% and the P value of the compari-
son of sham acupuncture and conventional therapy is
ⱕ5.0%, 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
a
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
b
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
c
7.6 ± 1.7 (387) 7.7 ± 1.8 (387) 7.7 ± 1.8 (388) 7.4 ± 1.9 (512)
Fear avoidance beliefs
d
3.3 ± 1.3 (387) 3.2 ± 1.3 (387) 3.3 ± 1.3 (388) 3.6 ± 1.2 (54)
Physical activity,
c
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).
a
Data are given as mean ± SD (number of patients) unless otherwise indicated.
b
Calculated as weight in kilograms divided by height in meters squared.
c
Not at all helpful, 0; extremely helpful, 10.
d
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
a
Type of
Acupuncture
Received
Type of
Acupuncture
Patients Stated
They Had
Received
Level of Confidence
of Patient Answers
TotalCertain Uncertain
Verum
(specific)
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)
377
Sham
(nonspecific)
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)
376
a
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.
ADVERSE EVENTS
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.
17
In ad-
dition, 476 clinically relevant adverse effects were reported
by 257 patients (22.6%), with no significant difference
between therapy groups (P= .81).
COMMENT
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.
5,18
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
19
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.”
20(p692)
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
21
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
a
Treatment Response
Therapy
Conventional
Sham
Acupuncture
Verum
Acupuncture
CPGS
Success
b
132 (34.1) 197 (50.9) 229 (59.2)
HFAQ
Success
c
195 (50.4) 251 (64.9) 281 (72.6)
Combined CPGS and HFAQ
Success
d
223 (57.6) 277 (71.6) 304 (78.5)
Total No. of patients 387 387 387
Combined GCPS, HFAQ,
and unblinded patients
Nonresponders
e
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
Nonresponders
f
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
limitations.
a
Values are given as number of patients (percentage).
b
Success was defined as 33% improvement or better on 3 pain-related items
on the GCPS.
c
Success was defined as 12% improvement or better on the back-specific
HFAQ.
d
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.
e
Patients who had no success in the combined CPGS, HFAQ, or unblinded
groups.
f
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
improvement.
Table 4. Primary Outcome: Pairwise Comparison
of Treatment Response 6 Months After Randomization
a
Treatment Response Intergroup Difference P Value
b
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
a
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.
b
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
22
)
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.
17
The
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-
tice.
23
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
6wk
a
60.7 (387) 59.2 (387) 56.1 (387)
3mo
b
55.0 (387) 51.9 (387) 41.9 (387)
Disability, HFAQ
b
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
c
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
d
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
d
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
c
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.
a
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.
b
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.
c
Low values better.
d
High values better.
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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
therapy.
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
.de).
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
.kks-netzwerk.de).
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