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ORIGINAL ARTICLE
SUMMARY
Introduction: Because the efficacy of acupuncture was not reliably substantiated by scientific
data, the Joint Federal Committee initiated a project comparing the effectiveness of acupuncture
to guideline-oriented conventional therapy for chronic pain. Four large, randomized studies
were conducted as part of the "German Acupuncture Trials" (GERAC). Methods: For the
studies on gonarthrosis and lumbalgia, 2 201 patients were randomised in eleven German
states (399 outpatient practices) to verum acupuncture, sham acupuncture and guidelineoriented conventional therapy. Primary outcome parameter was pain-dependent scores six
months after randomization. Parallel to the randomized studies, a Germany-wide cohort study
was conducted from which several samples were drawn to determine severe adverse events
(367 646 patients) and the efficacy of acupuncture under conditions of everyday medical
practice. Results: 10 to 15 acupuncture sessions, verum as well as sham, alleviated symptoms
more effectively than conventional therapy. The outcomes were comparable to the pain
dependent scores of patients in the knee and back-pain cohort samples. Discussion: Body
needle acupuncture is an effective method of pain reduction. Because of the results in GERAC,
the Joint Federal Committee of Physicians and Health Insurance Plans (Gemeinsamer
Bundesausschuss, G-BA) has recommended that acupuncture for both indications be treated
as a covered benefit under German public health insurance plans.
Dtsch Arztebl 2007; 104(3): A 12330.
Key words: Acupuncture, chronic pain, knee pain, osteoarthritis, adverse events, model project
hronic pain of degenerative origin in the back and knees is a common problem. These
types of pain are among the more common reasons for consulting a physician, with
lifetime prevalences of 70% to 85% for back pain (1) and 27% to 90% for knee pain (2). The
current national and international guidelines contain no recommendations for the treatment
of these conditions (2, 3). This is not surprising, as no randomized studies have yet shown
that any particular form of treatment for these conditions is superior to others (36). It has
been repeatedly found, however, that the provision of treatment yields better results than
simply placing patients on a waiting list.
One consequence of the current unsatisfactory therapeutic situation is the increasing
popularity of treatments from the realm of complementary medicine, e.g., acupuncture. The
efficacy of acupuncture for the treatment of pain has been documented in many randomized
controlled studies, many of which, however, were methodologically unsound. This conclusion
of the HTA report (e1) motivated the development of the German Model Project for
Acupuncture. In this article, we will present the findings of the GERAC studies on chronic
knee and back pain and discuss their therapeutic implications.
Methods
Cohort study
Acupuncture was made available nationwide for the treatment of chronic back or knee pain
by the state-regulated health insurance carriers, according to the provisions of the German
Model Project for Acupuncture. The project required that all patients who were treated with
acupuncture and were insured by one of the carriers financing the GERAC studies be
Abteilung Medizinische Informatik, Biometrie und Epidemiologie, Ruhr-Universitt Bochum (Dr. med. Dipl.-Chem. Endres); Institut
fr Medizinische Biometrie und Informatik, Universittsklinikum Heidelberg (Prof. Dr. rer. nat. Dipl.-Math. Victor); Orthopdische
Klinik der Universitt Regensburg (PD Dr. med. Haake); Institut fr Medizinische Biometrie und Informatik, Universittsklinikum
Heidelberg (Dr. sc. hum. Dipl.-Math. Witte); Klinik fr Ansthesiologie, Universittsklinikum Heidelberg (Dr. med. Streitberger);
Klinik fr Ansthesiologie, Intensiv-, Palliativ- und Schmerzmedizin, Berufsgenossenschaftliche Kliniken Bergmannsheil, RuhrUniversitt Bochum (Prof. Dr. med. Zenz)
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BOX
Inclusion criteria
age 40 years or older
chronic knee pain for at least 6 months
radiological confirmation of gonarthrosis with Kellgren-Lawrence score 2 or 3
WOMAC score at least 3 points
von Korff pain score at least 1 point
signed informed consent declaration
>
Exclusion criteria
knee pain due to other diseases (e.g., infections, systemic diseases, malignancy)
neurological or psychiatric disease
severe coagulopathy
medication abuse
pregnancy
prior acupuncture treatment for knee pain
acupuncture for any other indication in the last year
participation in another study
Inclusion criteria
age 18 years or older
chronic low back pain for at least 6 months
von Korff pain score at least 1 point
Hannover Score (functional questionnaire) < 70%
Treatment-free interval of at least 1 week
signed informed consent declaration
>
Exclusion criteria
low back pain due to other diseases (e.g., infections, systemic diseases, malignancy)
prior history of fracture, spinal surgery or disk surgery
scoliosis, kyphosis
neurological or psychiatric disease
severe coagulopathy
medication abuse
pregnancy
prior acupuncture treatment for low back pain
acupuncture for any other indication in the last year
participation in another study
reported to the data center in Bochum. The result was a nearly global collection of baseline
data on acupuncture patients across Germany. This part of the Model Project is described in
greater detail in the second publication on GERAC ("Acupuncture for the Treatment of
Chronic Headaches").
Acquisition of a sample of patients treated with acupuncture for gonarthrosis and
low back pain The ICD-10-coded indications M17 (gonarthrosis) and M54 (dorsalgia)
on the Model Project reporting forms were used to collect a representative sample of patients
treated with acupuncture for these conditions out of all the reporting forms submitted to the
data center in a six-week period. The sample contained 1 096 patients, representing just under
1 000 doctors' practices, who had undergone 10 acupuncture sessions in 10 weeks or less
(7). The patients were questioned by telephone twice, three and six months after treatment,
with respect to their acupuncture treatment and various dimensions of their painful condition,
particularly the following:
Dtsch Arztebl 2007; 104(3): A 12330 www.aerzteblatt.de
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Flowchart for the randomized GERAC knee and back pain studies (From: Endres HG, Zenz M, Schaub C et al.: Zur Problematik von Akupunkturstudien am Beispiel der Methodik von GERAC. Der Schmerz 2005; 19 (3) 202, with kind permission of Springer Verlag, Heidelberg.) After the
final interview (6 months after randomization), each patient was given a voucher for 10 (further) acupuncture treatments, to be redeemed
within 6 months.
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TABLE 1
Routine care: data on acupuncture treatments and pain tolerability before and after acupuncture
(cohort study sample)
Results
Cohort study
Data on pain tolerability and acupuncture are presented in table 1. The questionnaire scores
remained nearly unchanged from the 3-month to the 6-month interview (no worsening of
symptoms). Even six months after the last (tenth) acupuncture session, they were still
comparable to the values obtained in the randomized studies (diagram 2).
All further data are shown in tables 2a and 2b (7). An unexpected result was obtained
with regard to the patients' own assessment of treatment success, which was found to be
independent of indication and age, but dependent on sex: 66.2% of female patients, but
only 49.5% of male patients, rated the treatment outcome as "very good" or "good." The
physicians, immediately after the end of treatment, had a much more positive view: they
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DIAGRAM 2
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reported successful treatment (relief of pain) in 92% of all patients with knee pain and
94% of all patients with low back pain (11).
Randomized controlled trials
From February 2002 to March 2004, 3 333 patients were screened for the two orthopedic
indications, and 2 201 (66%) were randomized. The patient flow is shown in diagram 3.
Data over 6 six months could be obtained from 95.5% of all randomized patients. This yield
lies markedly above that of other, comparable studies (22, 23).
Because of randomization, the three treatment groups in each study did not differ at
baseline in their demographic characteristics, severity of illness, or medication use. The
detailed results of the gonarthrosis study will serve to illustrate those of both of the orthopedic
studies. Among the 1 039 patients initially randomized, 1 007 gave their informed consent
to participation in the study and were included in the intention-to-treat analysis. 22 patients
who did not complete the final interview were considered non-responders. Prolongation of
treatment to 15 sessions (i.e., visits to the doctor's office) was more common in the
acupuncture groups (verum 54.6%, sham 53.7%) than in the standard treatment group
(32.9%). In contrast, the patients in the standard treatment group made use of the offered
physiotherapeutic exercises more often than those in the acupuncture groups (standard
therapy, 11 sessions; verum acupuncture, 8.7; sham acupuncture, 8.8).
Treatment success, defined as a reduction of the WOMAC score by 36% or more, occurred
in 53.1% of the verum acupuncture patients, 51.0% of the sham acupuncture patients, and
29.1% of the patients treated with standard therapy. After removal of non-responders from the
data analysis, the corresponding figures were 34.7%, 37.3%, and 10.1%, respectively. Verum
and sham acupuncture both had a significantly better outcome than standard therapy (p<0.001
for both) but did not differ from each other (p = 0.479). Diagram 2 shows the temporal course
of the WOMAC and von Korff scores. Surprisingly, the verum scores are nearly identical to
those found in the cohort study. The results for the secondary endpoints are consistent with the
main result. None of the sensitivity analyses that were performed revealed any evidence of
other causes of the observed differences that were unrelated to treatment.
Another important result is the substantially lower use of analgesics by patients in the two
acupuncture groups. Non-steroidal anti-inflammatory drugs were used at least once in 26 weeks
by 496 patients overall (51.2% of the entire study group), including 47.6% of the patients
receiving verum acupuncture, 42.2% of the patients receiving sham acupuncture, and 65.3% of
the patients receiving standard treatment. Serious adverse events (SAEs) occurred in 45 of the
patients with knee pain (4.5%) and 51 of the patients with low back pain (4.5%); 57 of these
SAEs (59%) were in patients in the two acupuncture groups (table 3). The participating
physicians reported that there was no causal link between acupuncture and these events. The
study results are presented in detail in Witte et al. (e31) and Scharf et al. (25). The large number
of reported SAEs in both randomized studies and the comparatively small number in the cohort
studies together seem to imply that many SAEs were not reported in the cohort study (24).
Discussion
The four important results of the GERAC studies for orthopedic indications are as follows:
> Acupuncture is an effective treatment for chronic back or knee pain, leading to
clinically relevant reduction of pain and accompanying symptoms.
> Standard treatment of back or knee pain according to current guidelines is less effective
than acupuncture therapy.
> No difference between verum and sham acupuncture was found in any of the major
endpoints of the studies.
> The randomized studies and the cohort studies imply a persistent effect of acupuncture,
while the similarity of questionnaire scores at three and six months implies that the
treatment results obtained in the randomized studies did not differ significantly from
those obtained in routine care.
The lack of superiority of verum over sham acupuncture puts the major assumptions of
traditional Chinese medicine in question, in particular with regard to the choice of acupuncture
points, the depth of puncture (sham acupuncture was no more than 3 mm deep), and the
stimulation of the needles to obtain a feeling of de qi, which was not performed in the sham
acupuncture group. The effectiveness of both types of acupuncture can only be explained
Dtsch Arztebl 2007; 104(3): A 12330 www.aerzteblatt.de
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TABLE 2a
Cohort study: further findings from the questionnaires of patients with
knee pain
Questionnaire
3 months
(mean standard
deviation)
PGA*1
2.6 1.2
32.2 9.5
45.0 11.7
CES-D*3
15.6 6.3
*1PGA = Patient Global Assessment of treatment success, on a grading scale of 16 (1 = very good, 6 = fail).
*2SF-12 = 12-Item Short Form Health Survey, a quality-of-life questionnaire with subscales for physical
and mental health (higher values are better);
*3CES-D = Center for Epidemiological Studies Depression Scale, a depression questionnaire scored 060
(<18 is normal)
TABLE 2b
Cohort study: further findings from the questionnaires of patients with
back pain
Questionnaire
3 months
(mean standard
deviation)
41.8 20.6
1.7 1.0
PGA
2.4 1.3
35.8 10.1
45.3 10.5
CES-D
14.9 6.2
HFAQ*2
67.2 20.5
*1Von Korff pain intensity = questionnaire items 13, on a scale of 0100 (lower values are better),
von Korff total = all questionnaire items 17, on a scale of 0100 (lower values are better);
*2HFAQ = Hannover Functional Ability Questionnaire: extent of functional impairment (overall score up to
100%, with 60%70% signifying impairment, >70% normal);
PGA = Patient Global Assessment; CES-D = Center for Epidemiological Studies Depression Scale;
SF-12 = 12-Item Short Form Health Survey.
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DIAGRAM 3
Patient flowchart for the two randomized studies for orthopedic indications
TABLE 3
(Serious) adverse events (AEs, SAEs) in the randomized clinical trials
Verum
Knee pain study
Patients with at least 1 AE
Total number of AEs
Patients with at least 1 SAE
Total number of SAEs
Back pain study
Patients with at least 1 SAE
Total number of SAEs
Sham
Standard
N=326
N=365
N=316
91 (27.9%)
97 (26.6%)
97 (30.7%)
179
177
159
20 (6.1%)
9 (2.5%)
16 (5.1%)
23
18
N=387
N=387
N=388
14 (3.6%)
14 (3.6%)
2397 (5.9%)
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14
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of side effects, little stress for patients, and very few contraindications. Furthermore,
GERAC provides the first demonstration that acupuncture is superior to guideline-oriented
standard therapy. This proof of superiority was the basis for the Federal Joint Committee's
decision to accept acupuncture for the treatment of low back and knee pain in the catalog of
medical interventions that must be reimbursed by the statutory health insurance.
The most important consequence of the inclusion of acupuncture in the current treatment
concept for patients with chronic pain is that physicians are given a means of reducing their
patients' consumption of analgesics. Treating physicians should consider both options,
standard therapy and acupuncture. This is true even though no "scientific clothing" (e12)
has yet been found for the clinically relevant long-term effect of acupuncture. The same is
true of many conventional treatments.
This study was performed under the direction of the GERAC Studies Steering Committee: H. C. Diener (Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Germany), J. Kraemer (Orthopedic Clinic, Ruhr University Bochum), J. Michaelis (Institute for Medical Biostatistics, Epidemiology, and Informatics, University of Mainz), A. Molsberger (Acupuncture Research Group, Dsseldorf), H. Schaefer (Institute for Medical Biometrics and Epidemiology, University of Marburg), H.
J. Trampisch (Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum), N. Victor (Institute for
Medical Biometrics and Informatics, Heidelberg University Clinic), M. Zenz (Department of Anaesthesiology, Intensive Care, and
Pain Therapy, BG-Kliniken Bergmannsheil, Ruhr University Bochum).
Individual responsibilities: for the randomized study on gonarthrosis, Ruprecht Karls University, Heidelberg; for the randomized
study on low back pain, Philipps University, Marburg; for the cohort study, Ruhr University Bochum.
Directors of Clinical Testing: for gonarthrosis, Prof. Scharf (Heidelberg/Mannheim); for low back pain, PD Dr. Haake (Regensburg).
Model projects of the following health insurance carriers: AOK, BKK, IKK, Federal Miners' and Mine Employees' Insurance
Company (Bundesknappschaft), Federal Association of Agricultural Health Insurance Companies (Bundesverband der Landwirtschaftlichen Krankenkassen), and Seamen's Accident Prevention and Insurance Association (Seekasse).
Conflict of Interest Statement
Dr. Endress travel expenses were reimbursed by the Scientific Center of the German Society of Acupuncture Physicians
(Deutsche rztegesellschaft fr Akupunktur, DGfA).
Prof. Victor, PD Dr. Haake, Dr. Witte, Dr. Steinberger and Prof. Zenz declare that they have no conflict of interest according to the
guidelines of the International Committee of Medical Journal Editors.
Manuscript received on 10 April 2006, final version accepted on 10 November 2006.
Translated from the original German by Ethan Taub, M.D.
REFERENCES
1. Andersson GB: Epidemiological features of chronic low-back pain. Lancet 1999; 354: 5815.
2. AWM: Leitlinien der Orthopdie Gonarthrose. Deutsche Gesellschaft fr Orthopdie und Orthopdische Chirurgie
und Berufsverband der rzte fr Orthopdie, 2002.
3. Carragee EJ: Clinical practice. Persistent low back pain. N Engl J Med 2005; 352: 18918.
4. Ostelo RW, van Tulder MW, Vlaeyen JW, Linton SJ, Morley SJ, Assendelft WJ: Behavioural treatment for chronic
low-back pain. Cochrane Database Syst Rev 2005: CD002014.
5. Watson MC, Brookes ST, Faulkner A, Kirwan JR: Non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the knee. Cochrane Database Syst Rev 2006: CD000142.
6. Brosseau L, MacLeay L, Robinson V, Wells G, Tugwell P: Intensity of exercise for the treatment of osteoarthritis.
Cochrane Database Syst Rev 2003: CD004259.
7. Kukuk P, Lungenhausen M, Molsberger A, Endres HG: Long-term Improvement in Pain Coping for cLBP and
Gonarthrosis Patients Following Body Needle Acupuncture: A Prospective Cohort Study. Eur J Med Res 2005;
10: 26372.
8. Von Korff M, Ormel J, Keefe FJ, Dworkin SF: Grading the severity of chronic pain. Pain 1992; 50: 13349.
9. Collins SL, Edwards J, Moore RA, Smith LA, McQuay HJ: Seeking a simple measure of analgesia for mega-trials:
is a single global assessment good enough? Pain 2001; 91: 18994.
10. Stucki G, Meier D, Stucki S et al.: Evaluation einer deutschen Version des WOMAC (Western Ontario und
McMaster Universities) Arthroseindex. Z Rheumatol 1996; 55: 409.
11. Lungenhausen M, Endres HG, Kukuk P, Schaub C, Maier C, Zenz M: berschtzen rzte die Effekte der
Akupunkturbehandlung? Schmerz 2005;19: 50612.
12. Ware J Jr., Kosinski M, Keller SD: A 12-Item Short-Form Health Survey: construction of scales and preliminary
tests of reliability and validity. Med Care 1996; 34: 22033.
13. Endres HG, Zenz M, Schaub C et al.: Zur Problematik von Akupunkturstudien am Beispiel der Methodik von gerac.
Schmerz 2005; 19: 201204, 206, 208210 passim.
14. Haake M, Mller HH, Schade-Brittinger C et al.: The German multicenter, randomized, partially blinded,
prospective trial of acupuncture for chronic low-back pain: a preliminary report on the rationale and design of
the trial. J Altern Complement Med 2003; 9: 76370.
15. Streitberger K, Witte S, Mansmann U et al.: Efficacy and safety of acupuncture for chronic pain caused by
10
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gonarthrosis: A study protocol of an ongoing multi-centre randomised controlled clinical trial [ISRCTN27450856].
BMC Complementary and Alternative Medicine 2004; 4: 6.
16. Molsberger AF, Streitberger K, Kraemer J et al.: Designing an acupuncture study II: The nationwide, randomized,
controlled German acupuncture trials on low back pain and gonarthrosis (osteoarthritis). J Altern Complement
Med 2006; 12: 73342.
17. Hahn RA: The nocebo phenomenon: concept, evidence, and implications for public health. Preventive Medicine
1997; 26: 60711.
18. Nybo Andersen AM, Olsen J: Do interviewers' health beliefs and habits modify responses to sensitive questions?
A study using data collected from pregnant women by means of computer-assisted telephone interviews.
Am J Epidemiol 2002; 155: 95100.
19. Goldsmith CH, Boers M, Bombardier C, Tugwell P: Criteria for clinically important changes in outcomes: development,
scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. J Rheumatol 1993;
20: 5615.
20. Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL: Defining the clinically important difference in pain outcome
measures. Pain 2000; 88: 28794.
21. Kohlmann T, Raspe H: Der Funktionsfragebogen Hannover zur alltagsnahen Diagnostik der Funktionsbeeintrchtigung
durch Rckenschmerzen (FFbH-R). Rehabilitation 1996; 35: IVIII.
22. Witt C, Brinkhaus B, Jena S et al.: Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet
2005; 366: 13643.
23. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AMK, Hochberg MC: Effectiveness of acupuncture as adjunctive
therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2004; 141: 90110.
24. Endres HG, Molsberger A, Lungenhausen M, Trampisch HJ: An internal standard for verifying the accuracy of
serious adverse event reporting: the example of an acupuncture study of 190,924 patients. Eur J Med Res 2004;
9: 54551.
25. Scharf H-P, Mansmann U, Streitberger K et al.: Acupuncture and Knee Osteoarthritis: A Three-Armed Randomized
Trial. Ann Intern Med 2006; 145: 1220.
Corresponding author
Dr. med. Dipl.-Chem. Heinz G. Endres
Ruhr University Bochum
Department of Medical Informatics, Biometrics and Epidemiology
D-44870 Bochum, Germany
heinz.endres@ruhr-uhi-bochum.de
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