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Claudia M. Witt, Susanne Jena, Dagmar Selim, Benno Brinkhaus, Thomas Reinhold, Katja Wruck, Bodo Liecker, Klaus Linde, Karl Wegscheider, Stefan N. Willich, Pragmatic Randomized Trial Evaluating the Clinical and Economic Effectiveness of Acupuncture for Chronic Low Back Pain, American Journal of Epidemiology, Volume 164, Issue 5, 1 September 2006, Pages 487–496, https://doi.org/10.1093/aje/kwj224
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Abstract
In a randomized controlled trial plus a nonrandomized cohort, the authors investigated the effectiveness and costs of acupuncture in addition to routine care in the treatment of chronic low back pain and assessed whether the effects of acupuncture differed in randomized and nonrandomized patients. In 2001, German patients with chronic low back pain were allocated to an acupuncture group or a no-acupuncture control group. Persons who did not consent to randomization were included in a nonrandomized acupuncture group. All patients were allowed to receive routine medical care in addition to study treatment. Back function (Hannover Functional Ability Questionnaire), pain, and quality of life were assessed at baseline and after 3 and 6 months, and cost-effectiveness was analyzed. Of 11,630 patients (mean age = 52.9 years (standard deviation, 13.7); 59% female), 1,549 were randomized to the acupuncture group and 1,544 to the control group; 8,537 were included in the nonrandomized acupuncture group. At 3 months, back function improved by 12.1 (standard error (SE), 0.4) to 74.5 (SE, 0.4) points in the acupuncture group and by 2.7 (SE, 0.4) to 65.1 (SE, 0.4) points among controls (difference = 9.4 points (95% confidence interval 8.3, 10.5); p < 0.001). Nonrandomized patients had more severe symptoms at baseline and showed improvements in back function similar to those seen in randomized patients. The incremental cost-effectiveness ratio was €10,526 (euros) per quality-adjusted life year. Acupuncture plus routine care was associated with marked clinical improvements in these patients and was relatively cost-effective.
Low back pain has a lifetime prevalence of more than 70 percent of the population in Western industrialized countries and represents a major economic burden (1). Although 90 percent of acute episodes resolve within 6 weeks, up to 7 percent of patients develop chronic pain (1). The therapeutic management of chronic low back pain varies widely, and the effectiveness of a number of conventional standard treatments has yet to be clearly established (2). According to recent surveys, the number of patients with chronic pain who use complementary and alternative medicine is growing (3–5). Acupuncture is a widely used treatment, especially for chronic low back pain (3), and back pain is the most common reason for visits to acupuncturists (6). However, systematic reviews have shown that the evidence produced by previous trials on the effectiveness of acupuncture is inconclusive because of inconsistent results, low methodological quality, and small sample sizes (7–9). In contrast, two recent meta-analyses demonstrated that acupuncture is more effective than sham treatment for short-term pain relief (10, 11). However, the majority of previous trials were designed as experimental studies; as a result, there is currently very little information about the effectiveness and cost-effectiveness of acupuncture in general medical practice.
In Germany, acupuncture is administered primarily by physicians. Before the year 2000, a number of German health insurance companies covered the costs of acupuncture treatment, at least in part. Under increasing budgetary pressure, however, the German Federal Committee of Physicians and Health Insurers proposed in 2000 that large research initiatives on acupuncture be conducted for several pain syndromes and recommended that patients be reimbursed for the costs of acupuncture only if they participated in such studies (12). We designed the present study as a pragmatic trial to investigate the effectiveness and cost of acupuncture in addition to routine care among patients with chronic low back pain, as compared with routine care alone. In addition, we examined whether the effects of acupuncture differ in randomized and nonrandomized patients, whether treatment effects last over a longer period of time in acupuncture patients, and whether specific patient and physician characteristics are associated with particular treatment outcomes.
MATERIALS AND METHODS
Design
The Acupuncture in Routine Care Study consisted of a multicenter, randomized controlled trial and a nonrandomized cohort. Patients who agreed to randomization were allocated to an acupuncture group that received immediate acupuncture treatment or a control group that received delayed acupuncture treatment 3 months later. Patients who declined to be randomized were included in a third arm of the study and also received immediate acupuncture treatment (nonrandomized acupuncture group). The study period per patient was 6 months and comprised a 3-month treatment phase followed by 3 months of follow-up.
The Acupuncture in Routine Care Study is part of a large acupuncture research initiative funded by a group of social health insurance funds that provide coverage to approximately 10 percent of the German population. The study protocol was approved by the local ethics review boards, and the study itself was conducted according to standard guidelines (i.e., the Declaration of Helsinki and European Epidemiology Federation Good Epidemiological Practice) (13). All study participants provided written, informed consent.
Patients
Patients insured by one of the participating social health insurance funds were recruited after they contacted a participating physician because of chronic low back pain. If a patient requested acupuncture or if the physician considered acupuncture to be a suitable treatment option, the patient was informed about the study. Subjects who met the inclusion criteria and provided informed consent were randomized using a central telephone randomization procedure. For randomization, we used blocks of 10 patients, and the random list was generated with SAS software (SAS Institute, Inc., Cary, North Carolina).
Patients were included in the study only if we received both the physician's baseline questionnaire and the patient's consent form following randomization. Upon successful inclusion in the study, patients were sent the baseline questionnaire by standard mail. To be included in the study, a patient had to meet the following criteria: clinical diagnosis of chronic low back pain with disease duration of more than 6 months; age ≥18 years; and provision of written informed consent. The exclusion criteria were: protusio or prolapse of one or more intervertebral discs with concurrent neurologic symptoms; prior vertebral column surgery; infectious spondylopathy; low back pain caused by inflammatory, malignant, or autoimmune disease; congenital deformation of the spine, except for slight lordosis or scoliosis; compression fracture caused by osteoporosis; spinal stenosis; and spondylolysis or spondylolisthesis.
Interventions
Physicians interested in participating in the study were required to have at least an A-diploma, a German diploma representing 140 hours of certified acupuncture education. This education and other training include wide variations in style and acupuncture technique.
Each patient received a maximum of 15 acupuncture sessions. To assess the effectiveness of acupuncture in general medical practice, we left the acupuncture points and the number of needles used to the discretion of each physician. Only needle acupuncture (with disposable one-time needles and manual stimulation) was allowed; other forms of acupuncture treatment, such as laser acupuncture, were not permitted. In all three treatment groups, the patients were allowed to use additional conventional treatments as needed.
In accordance with German federal regulations, the participating social health insurance funds covered 100 percent of the acupuncture costs for patients who agreed to randomization and 90 percent of the costs for patients who participated in the study but did not agree to randomization.
Outcome measurements
Patients completed standardized questionnaires, which included questions on sociodemographic characteristics, at baseline and after 3 or 6 months. Because of the large number of patients participating in the nonrandomized acupuncture group, a random sample of 50 percent received the questionnaire after 6 months. The primary outcome measure was back function at 3 months, as assessed by the validated Hannover Functional Ability Questionnaire (HFAQ; in German, Funktionsfragebogen Hannover Rücken) (14). The HFAQ rates back function on a scale from 0 to 100, with 100 representing perfect back function.
In order to give this variable the same orientation as the back pain scale (higher values indicating worse outcomes), we used the difference between 100 and the HFAQ value for analysis and called it “back function loss.” As an outcome measure, we used the percent reduction of back function loss, since in all three groups reductions were roughly proportional to the baseline back function loss. If back function loss increased for an individual patient during follow-up, the percentage was calculated with respect to the maximum possible loss and given a negative sign. Patients who showed an improvement of at least 20 percent for the variable “back function loss” were considered to be treatment responders.
As further secondary outcome parameters after 3 months, we calculated percent reductions for the Low Back Pain Rating Scale (15) and absolute changes from baseline for Medical Outcomes Study 36-Item Short Form (SF-36) component scales (16) to assess health-related quality of life. Data on the adjunctive use of analgesics were provided by the participating health insurance companies. Side effects were evaluated using patient and physician questionnaires after 3 months. In order to study the durability of any therapeutic benefit in the acupuncture groups and the effect of delayed acupuncture treatment in the control group, changes from baseline to 6 months were calculated analogously.
Statistics
Confirmatory testing of the primary and secondary outcome measures (carried out with SPSS, version 11.5; SPSS, Inc., Chicago, Illinois) was based on the entire study population using the full data set. Sensitivity analyses were performed for the primary outcome measure, either by replacing missing data according to the “last value carried forward” principle or by using various hot deck methods or regression-based multiple imputation. The test procedure was performed in order to maintain a global significance level of α = 5 percent. Using covariance analysis, we tested the two-sided null hypothesis, H0: mean HFAQ score after 3 months for the acupuncture group = mean HFAQ score after 3 months for controls. With 366 patients per group and α = 5 percent, the study would have had 90 percent power to detect a difference of 12 percent (9.36 points) in the back function score (HFAQ), assuming a mean score of 78 points and a standard deviation of 39 in the control/acupuncture group. However, we decided to increase the number of patients per group to 1,500, thus allowing a larger number of physicians to participate and increasing the applicability of our findings, as well as the reliability of our analysis of possible predictors.
To identify factors affecting improvements in back function or back pain and to better understand the patient selection due to the acceptance of randomization, we fitted linear mixed models for back function loss and back pain to the data of all study patients. We chose mixed models to comply with the potential cluster structure of the data, because several patients were included by the same physician. As potential regressors, we prespecified several characteristics of the physicians (age, years of professional experience, type of acupuncture diploma, hours of acupuncture training, years of acupuncture experience, diagnosis in the context of traditional Chinese medicine, and percentage of practice time with acupuncture treatment) and several characteristics of the patients (sex, age, education, baseline physical and mental quality-of-life scores, back function and back pain, the duration of complaints prior to the study, and the study group to which each patient was assigned) before the study started. For the final model, we selected significant variables in a stepwise backwards procedure based on likelihood ratio tests. In addition, we considered the selected regressors as potential modifiers of the acupuncture effect and added the corresponding interaction terms to the model, backwards-selecting them if they were significant. All reported p values are two-sided.
Economic analyses
The cost perspective was societal. Data analysis included 1) overall costs during the 3 months after randomization (including costs not related to chronic low back pain) and 2) only diagnosis-specific costs, using International Classification of Diseases, Tenth Revision, codes to identify costs due to chronic low back pain and related conditions. Direct health-related costs for physician visits, hospital stays, medication, acupuncture treatment, and number of sick-leave days were provided by the participating social health insurance funds. Because the observation period was 6 months in length, there was no need to discount any costs or effects.
The net benefit approach (21) was used to measure the acceptability curve of incremental cost-effectiveness against a societal threshold value λ, which is often described as society's willingness to pay for one extra QALY gained. In the United Kingdom, a threshold of £30,000 (pounds) per QALY is found to be consistent with decisions for adopting new technologies (22). Because such a threshold does not yet exist in Germany, we used an arbitrary and hypothetical threshold of €50,000 (euros) per QALY. For a given value of λ, an intervention would be considered cost-effective if its net benefit were greater than zero—in other words, if the incremental cost-effectiveness ratio were below λ. Thus, a new treatment should be adopted if the net benefit under λ is greater than zero (23).
RESULTS
Patient inclusion, baseline characteristics, and treatment
Between January and September of 2001, a total of 11,630 patients with chronic low back pain were recruited for the study by 3,486 study physicians (see figure 1 for patient selection). A total of 3,093 patients accepted randomization and were allocated to the acupuncture group or the control group. Two hundred and fifty-two patients (98 acupuncture, 154 control) could not be included in the analysis because the study office did not receive their consent forms. The remaining 11,378 patients (1,451 acupuncture, 1,390 control, and 8,537 nonrandomized acupuncture) were included in the analysis. After 3 months, data were available for 91 percent of the patients (1,363 acupuncture, 1,260 control, and 7,767 nonrandomized acupuncture).
The randomized groups were comparable with regard to all baseline characteristics (see table 1). Between the randomized and nonrandomized acupuncture groups, however, there were significant differences. Patients who did not consent to randomization were more likely to have had more than 10 years of schooling than randomized patients. Nonrandomized patients were also more likely to have experienced more severe complaints, and they had, on average, suffered from chronic low back pain for 1 year less than randomized patients. During the first 3 months, patients in the acupuncture groups received 10.4 (standard deviation (SD), 3.0) acupuncture sessions (randomized acupuncture, 10.4 (SD, 2.6); nonrandomized acupuncture, 10.3 (SD, 3.1); p = 0.40). Most patients (74 percent) received 5–10 sessions, whereas 21 percent received more than 10 sessions and 5 percent received fewer than five sessions.
Parameter . | Randomized groups . | . | . | Acupuncture groups . | . | p value† . | Total (N = 11,378) . | |||
---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture (n = 1,451) . | Control (n = 1,390) . | p value . | Randomized (n = 2,841) . | Nonrandomized (n = 8,537) . | . | . | |||
Female sex (no. and %) | 837 (57.7) | 791 (56.9) | 0.675 | 1,627 (57.3) | 5,061 (59.3) | 0.167 | 6,689 (58.8) | |||
Age (years) | 53.1 (13.5) | 52.6 (13.2) | 0.370 | 52.8 (13.3) | 52.9 (13.8) | 0.731 | 52.9 (13.7) | |||
>10 years of schooling (%) | 25.8 | 29.2 | 0.083 | 27.4 | 30.8 | 0.008 | 26.0 | |||
Duration of disease (years) | 7.2 (8.0) | 7.2 (7.8) | 0.820 | 7.2 (7.9) | 6.1 (7.6) | <0.001 | 6.3 (7.8) | |||
Back function score (HFAQ‡) | 61.8 (21.0) | 63.3 (20.8) | 0.067 | 62.5 (20.9) | 60.6 (22.0) | <0.001 | 61.1 (21.7) | |||
Back pain score (Low Back Pain Rating Scale§) | 25.5 (12.3) | 25.0 (12.1) | 0.327 | 25.3 (12.2) | 26.0 (12.4) | 0.005 | 25.8 (12.4) | |||
Quality of life score (SF-36‡) | ||||||||||
Physical component | 34.3 (9.0) | 34.6 (9.6) | 0.463 | 34.5 (9.3) | 33.8 (9.1) | 0.002 | 34.0 (9.2) | |||
Mental component | 43.3 (10.3) | 43.5 (10.1) | 0.544 | 43.4 (10.2) | 43.5 (10.2) | 0.574 | 43.5 (10.2) |
Parameter . | Randomized groups . | . | . | Acupuncture groups . | . | p value† . | Total (N = 11,378) . | |||
---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture (n = 1,451) . | Control (n = 1,390) . | p value . | Randomized (n = 2,841) . | Nonrandomized (n = 8,537) . | . | . | |||
Female sex (no. and %) | 837 (57.7) | 791 (56.9) | 0.675 | 1,627 (57.3) | 5,061 (59.3) | 0.167 | 6,689 (58.8) | |||
Age (years) | 53.1 (13.5) | 52.6 (13.2) | 0.370 | 52.8 (13.3) | 52.9 (13.8) | 0.731 | 52.9 (13.7) | |||
>10 years of schooling (%) | 25.8 | 29.2 | 0.083 | 27.4 | 30.8 | 0.008 | 26.0 | |||
Duration of disease (years) | 7.2 (8.0) | 7.2 (7.8) | 0.820 | 7.2 (7.9) | 6.1 (7.6) | <0.001 | 6.3 (7.8) | |||
Back function score (HFAQ‡) | 61.8 (21.0) | 63.3 (20.8) | 0.067 | 62.5 (20.9) | 60.6 (22.0) | <0.001 | 61.1 (21.7) | |||
Back pain score (Low Back Pain Rating Scale§) | 25.5 (12.3) | 25.0 (12.1) | 0.327 | 25.3 (12.2) | 26.0 (12.4) | 0.005 | 25.8 (12.4) | |||
Quality of life score (SF-36‡) | ||||||||||
Physical component | 34.3 (9.0) | 34.6 (9.6) | 0.463 | 34.5 (9.3) | 33.8 (9.1) | 0.002 | 34.0 (9.2) | |||
Mental component | 43.3 (10.3) | 43.5 (10.1) | 0.544 | 43.4 (10.2) | 43.5 (10.2) | 0.574 | 43.5 (10.2) |
All data shown are mean values with standard deviations in parentheses, except for sex (number and percentage) and schooling (percentage).
Two-sided t test or χ2 test.
HFAQ, Hannover Functional Ability Questionnaire; SF-36, Medical Outcomes Study 36-Item Short Form.
Lower values indicate less pain.
Parameter . | Randomized groups . | . | . | Acupuncture groups . | . | p value† . | Total (N = 11,378) . | |||
---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture (n = 1,451) . | Control (n = 1,390) . | p value . | Randomized (n = 2,841) . | Nonrandomized (n = 8,537) . | . | . | |||
Female sex (no. and %) | 837 (57.7) | 791 (56.9) | 0.675 | 1,627 (57.3) | 5,061 (59.3) | 0.167 | 6,689 (58.8) | |||
Age (years) | 53.1 (13.5) | 52.6 (13.2) | 0.370 | 52.8 (13.3) | 52.9 (13.8) | 0.731 | 52.9 (13.7) | |||
>10 years of schooling (%) | 25.8 | 29.2 | 0.083 | 27.4 | 30.8 | 0.008 | 26.0 | |||
Duration of disease (years) | 7.2 (8.0) | 7.2 (7.8) | 0.820 | 7.2 (7.9) | 6.1 (7.6) | <0.001 | 6.3 (7.8) | |||
Back function score (HFAQ‡) | 61.8 (21.0) | 63.3 (20.8) | 0.067 | 62.5 (20.9) | 60.6 (22.0) | <0.001 | 61.1 (21.7) | |||
Back pain score (Low Back Pain Rating Scale§) | 25.5 (12.3) | 25.0 (12.1) | 0.327 | 25.3 (12.2) | 26.0 (12.4) | 0.005 | 25.8 (12.4) | |||
Quality of life score (SF-36‡) | ||||||||||
Physical component | 34.3 (9.0) | 34.6 (9.6) | 0.463 | 34.5 (9.3) | 33.8 (9.1) | 0.002 | 34.0 (9.2) | |||
Mental component | 43.3 (10.3) | 43.5 (10.1) | 0.544 | 43.4 (10.2) | 43.5 (10.2) | 0.574 | 43.5 (10.2) |
Parameter . | Randomized groups . | . | . | Acupuncture groups . | . | p value† . | Total (N = 11,378) . | |||
---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture (n = 1,451) . | Control (n = 1,390) . | p value . | Randomized (n = 2,841) . | Nonrandomized (n = 8,537) . | . | . | |||
Female sex (no. and %) | 837 (57.7) | 791 (56.9) | 0.675 | 1,627 (57.3) | 5,061 (59.3) | 0.167 | 6,689 (58.8) | |||
Age (years) | 53.1 (13.5) | 52.6 (13.2) | 0.370 | 52.8 (13.3) | 52.9 (13.8) | 0.731 | 52.9 (13.7) | |||
>10 years of schooling (%) | 25.8 | 29.2 | 0.083 | 27.4 | 30.8 | 0.008 | 26.0 | |||
Duration of disease (years) | 7.2 (8.0) | 7.2 (7.8) | 0.820 | 7.2 (7.9) | 6.1 (7.6) | <0.001 | 6.3 (7.8) | |||
Back function score (HFAQ‡) | 61.8 (21.0) | 63.3 (20.8) | 0.067 | 62.5 (20.9) | 60.6 (22.0) | <0.001 | 61.1 (21.7) | |||
Back pain score (Low Back Pain Rating Scale§) | 25.5 (12.3) | 25.0 (12.1) | 0.327 | 25.3 (12.2) | 26.0 (12.4) | 0.005 | 25.8 (12.4) | |||
Quality of life score (SF-36‡) | ||||||||||
Physical component | 34.3 (9.0) | 34.6 (9.6) | 0.463 | 34.5 (9.3) | 33.8 (9.1) | 0.002 | 34.0 (9.2) | |||
Mental component | 43.3 (10.3) | 43.5 (10.1) | 0.544 | 43.4 (10.2) | 43.5 (10.2) | 0.574 | 43.5 (10.2) |
All data shown are mean values with standard deviations in parentheses, except for sex (number and percentage) and schooling (percentage).
Two-sided t test or χ2 test.
HFAQ, Hannover Functional Ability Questionnaire; SF-36, Medical Outcomes Study 36-Item Short Form.
Lower values indicate less pain.
Randomized comparisons
The course of back function in the two randomized groups, as well as in the nonrandomized group, is depicted in figure 2. In the primary analysis after 3 months, back function improvement was more pronounced in the acupuncture group than in the control group (mean HFAQ scores increased by 12.1 (standard error (SE), 0.4) to 74.5 (SE, 0.4) points in the acupuncture group and by 2.7 (SE, 0.4) to 65.1 (SE, 0.4) points in the control group; difference = 9.4 points (95 percent confidence interval (CI): 8.3, 10.5); p < 0.001), after adjustment for baseline differences.
This improvement was robust in the sensitivity analyses for missing data; indeed, the smallest difference between the acupuncture and control groups was 7.0 (p < 0.001). The proportion of responders was 52.6 percent in the acupuncture group as compared with 26.8 percent in the control group (p < 0.001), the absolute risk reduction was 25.8 percent, and the number needed to treat was 4.
For back function loss, back pain, and quality of life (on both SF-36 component scores), 3-month improvement was significantly more pronounced in the acupuncture group than in the control group (see table 2). There were no significant differences between the acupuncture and control groups with regard to the number of patients prescribed analgesics during the 3 months following randomization (acupuncture group, 21.1 percent of patients; control group, 22.7 percent of patients; p = 0.29).
Parameter . | Randomized groups . | . | . | . | Nonrandomized group . | Nonrandomized vs. randomized . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture . | Control . | Acupuncture vs. control . | . | . | . | . | ||||
. | . | . | Difference . | p value† . | . | Difference . | p value† . | ||||
Back function and back pain | Reduction (%) | Reduction (%) | Reduction (%) | ||||||||
3-month change from baseline | |||||||||||
Back function loss (HFAQ‡) | 33.3 (31.4, 35.3) | 11.3 (9.5, 13.1) | 22.0 (19.3, 24.7) | <0.001 | 35.5 (34.7, 36.4) | 2.2 (0.1, 4.4) | 0.044 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 37.0 (35.2, 38.9) | 9.8 (7.9, 11.7) | 27.2 (24.5, 20.9) | <0.001 | 39.4 (38.6, 40.1) | 2.3 (0.3, 4.3) | 0.023 | ||||
6-month change from baseline¶ | |||||||||||
Back function loss (HFAQ) | 32.4 (30.3, 34.4) | 28.6 (26.5, 30.8) | 3.7 (0.7, 6.7) | 0.015 | 35.5 (34.3, 36.8) | 3.2 (0.7, 5.7) | 0.012 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 33.5 (31.4, 35.7) | 30.8 (28.7, 33.0) | 2.7 (–0.3, 5.7) | 0.082 | 37.0 (35.7, 38.2) | 3.4 ( 0.9, 5.9) | 0.007 | ||||
Quality of life (SF-36‡) | Mean increase (points) | Mean increase (points) | Mean increase (points) | ||||||||
3-month change from baseline | |||||||||||
Physical component score | 7.0 (6.5, 7.5) | 2.3 (1.8, 2.8) | 4.7 (4.0, 5.4) | <0.001 | 7.9 (7.7, 8.1) | 0.8 (0.3, 1.4) | 0.004 | ||||
Mental component score | 2.4 (1.9, 2.9) | 0.3 (–0.2, 0.8) | 2.1 (1.4, 2.8) | <0.001 | 2.1 (1.9, 2.4) | –0.2 (–0.8, 0.3) | 0.356 | ||||
6-month change from baseline¶ | |||||||||||
Physical component score | 6.9 (6.3, 7.4) | 6.3 (5.8, 6.9) | 0.6 (–0.2, 1.3) | 0.154 | 8.0 (7.6, 8.3) | 1.1 (0.4, 1.7) | 0.002 | ||||
Mental component score | 1.5 (1.0, 2.0) | 1.3 (0.8, 1.9) | 0.2 (–0.6, 1.0) | 0.607 | 1.7 (1.4, 2.0) | 0.2 (–0.4, 0.8) | 0.535 |
Parameter . | Randomized groups . | . | . | . | Nonrandomized group . | Nonrandomized vs. randomized . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture . | Control . | Acupuncture vs. control . | . | . | . | . | ||||
. | . | . | Difference . | p value† . | . | Difference . | p value† . | ||||
Back function and back pain | Reduction (%) | Reduction (%) | Reduction (%) | ||||||||
3-month change from baseline | |||||||||||
Back function loss (HFAQ‡) | 33.3 (31.4, 35.3) | 11.3 (9.5, 13.1) | 22.0 (19.3, 24.7) | <0.001 | 35.5 (34.7, 36.4) | 2.2 (0.1, 4.4) | 0.044 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 37.0 (35.2, 38.9) | 9.8 (7.9, 11.7) | 27.2 (24.5, 20.9) | <0.001 | 39.4 (38.6, 40.1) | 2.3 (0.3, 4.3) | 0.023 | ||||
6-month change from baseline¶ | |||||||||||
Back function loss (HFAQ) | 32.4 (30.3, 34.4) | 28.6 (26.5, 30.8) | 3.7 (0.7, 6.7) | 0.015 | 35.5 (34.3, 36.8) | 3.2 (0.7, 5.7) | 0.012 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 33.5 (31.4, 35.7) | 30.8 (28.7, 33.0) | 2.7 (–0.3, 5.7) | 0.082 | 37.0 (35.7, 38.2) | 3.4 ( 0.9, 5.9) | 0.007 | ||||
Quality of life (SF-36‡) | Mean increase (points) | Mean increase (points) | Mean increase (points) | ||||||||
3-month change from baseline | |||||||||||
Physical component score | 7.0 (6.5, 7.5) | 2.3 (1.8, 2.8) | 4.7 (4.0, 5.4) | <0.001 | 7.9 (7.7, 8.1) | 0.8 (0.3, 1.4) | 0.004 | ||||
Mental component score | 2.4 (1.9, 2.9) | 0.3 (–0.2, 0.8) | 2.1 (1.4, 2.8) | <0.001 | 2.1 (1.9, 2.4) | –0.2 (–0.8, 0.3) | 0.356 | ||||
6-month change from baseline¶ | |||||||||||
Physical component score | 6.9 (6.3, 7.4) | 6.3 (5.8, 6.9) | 0.6 (–0.2, 1.3) | 0.154 | 8.0 (7.6, 8.3) | 1.1 (0.4, 1.7) | 0.002 | ||||
Mental component score | 1.5 (1.0, 2.0) | 1.3 (0.8, 1.9) | 0.2 (–0.6, 1.0) | 0.607 | 1.7 (1.4, 2.0) | 0.2 (–0.4, 0.8) | 0.535 |
All data are percentages or mean point increases, with 95% confidence intervals shown in parentheses.
Two-sided t test.
HFAQ, Hannover Functional Ability Questionnaire; SF-36, Medical Outcomes Study 36-Item Short Form.
Lower values indicate less pain.
The control group also received acupuncture.
Parameter . | Randomized groups . | . | . | . | Nonrandomized group . | Nonrandomized vs. randomized . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture . | Control . | Acupuncture vs. control . | . | . | . | . | ||||
. | . | . | Difference . | p value† . | . | Difference . | p value† . | ||||
Back function and back pain | Reduction (%) | Reduction (%) | Reduction (%) | ||||||||
3-month change from baseline | |||||||||||
Back function loss (HFAQ‡) | 33.3 (31.4, 35.3) | 11.3 (9.5, 13.1) | 22.0 (19.3, 24.7) | <0.001 | 35.5 (34.7, 36.4) | 2.2 (0.1, 4.4) | 0.044 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 37.0 (35.2, 38.9) | 9.8 (7.9, 11.7) | 27.2 (24.5, 20.9) | <0.001 | 39.4 (38.6, 40.1) | 2.3 (0.3, 4.3) | 0.023 | ||||
6-month change from baseline¶ | |||||||||||
Back function loss (HFAQ) | 32.4 (30.3, 34.4) | 28.6 (26.5, 30.8) | 3.7 (0.7, 6.7) | 0.015 | 35.5 (34.3, 36.8) | 3.2 (0.7, 5.7) | 0.012 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 33.5 (31.4, 35.7) | 30.8 (28.7, 33.0) | 2.7 (–0.3, 5.7) | 0.082 | 37.0 (35.7, 38.2) | 3.4 ( 0.9, 5.9) | 0.007 | ||||
Quality of life (SF-36‡) | Mean increase (points) | Mean increase (points) | Mean increase (points) | ||||||||
3-month change from baseline | |||||||||||
Physical component score | 7.0 (6.5, 7.5) | 2.3 (1.8, 2.8) | 4.7 (4.0, 5.4) | <0.001 | 7.9 (7.7, 8.1) | 0.8 (0.3, 1.4) | 0.004 | ||||
Mental component score | 2.4 (1.9, 2.9) | 0.3 (–0.2, 0.8) | 2.1 (1.4, 2.8) | <0.001 | 2.1 (1.9, 2.4) | –0.2 (–0.8, 0.3) | 0.356 | ||||
6-month change from baseline¶ | |||||||||||
Physical component score | 6.9 (6.3, 7.4) | 6.3 (5.8, 6.9) | 0.6 (–0.2, 1.3) | 0.154 | 8.0 (7.6, 8.3) | 1.1 (0.4, 1.7) | 0.002 | ||||
Mental component score | 1.5 (1.0, 2.0) | 1.3 (0.8, 1.9) | 0.2 (–0.6, 1.0) | 0.607 | 1.7 (1.4, 2.0) | 0.2 (–0.4, 0.8) | 0.535 |
Parameter . | Randomized groups . | . | . | . | Nonrandomized group . | Nonrandomized vs. randomized . | . | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
. | Acupuncture . | Control . | Acupuncture vs. control . | . | . | . | . | ||||
. | . | . | Difference . | p value† . | . | Difference . | p value† . | ||||
Back function and back pain | Reduction (%) | Reduction (%) | Reduction (%) | ||||||||
3-month change from baseline | |||||||||||
Back function loss (HFAQ‡) | 33.3 (31.4, 35.3) | 11.3 (9.5, 13.1) | 22.0 (19.3, 24.7) | <0.001 | 35.5 (34.7, 36.4) | 2.2 (0.1, 4.4) | 0.044 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 37.0 (35.2, 38.9) | 9.8 (7.9, 11.7) | 27.2 (24.5, 20.9) | <0.001 | 39.4 (38.6, 40.1) | 2.3 (0.3, 4.3) | 0.023 | ||||
6-month change from baseline¶ | |||||||||||
Back function loss (HFAQ) | 32.4 (30.3, 34.4) | 28.6 (26.5, 30.8) | 3.7 (0.7, 6.7) | 0.015 | 35.5 (34.3, 36.8) | 3.2 (0.7, 5.7) | 0.012 | ||||
Back pain loss (Low Back Pain Rating Scale§) | 33.5 (31.4, 35.7) | 30.8 (28.7, 33.0) | 2.7 (–0.3, 5.7) | 0.082 | 37.0 (35.7, 38.2) | 3.4 ( 0.9, 5.9) | 0.007 | ||||
Quality of life (SF-36‡) | Mean increase (points) | Mean increase (points) | Mean increase (points) | ||||||||
3-month change from baseline | |||||||||||
Physical component score | 7.0 (6.5, 7.5) | 2.3 (1.8, 2.8) | 4.7 (4.0, 5.4) | <0.001 | 7.9 (7.7, 8.1) | 0.8 (0.3, 1.4) | 0.004 | ||||
Mental component score | 2.4 (1.9, 2.9) | 0.3 (–0.2, 0.8) | 2.1 (1.4, 2.8) | <0.001 | 2.1 (1.9, 2.4) | –0.2 (–0.8, 0.3) | 0.356 | ||||
6-month change from baseline¶ | |||||||||||
Physical component score | 6.9 (6.3, 7.4) | 6.3 (5.8, 6.9) | 0.6 (–0.2, 1.3) | 0.154 | 8.0 (7.6, 8.3) | 1.1 (0.4, 1.7) | 0.002 | ||||
Mental component score | 1.5 (1.0, 2.0) | 1.3 (0.8, 1.9) | 0.2 (–0.6, 1.0) | 0.607 | 1.7 (1.4, 2.0) | 0.2 (–0.4, 0.8) | 0.535 |
All data are percentages or mean point increases, with 95% confidence intervals shown in parentheses.
Two-sided t test.
HFAQ, Hannover Functional Ability Questionnaire; SF-36, Medical Outcomes Study 36-Item Short Form.
Lower values indicate less pain.
The control group also received acupuncture.
Nonrandomized comparisons
At 3 months, back function improvement was more pronounced in the nonrandomized acupuncture group than in the randomized acupuncture group (mean HFAQ scores increased by 12.1 (SE, 0.4) to 74.5 (SE, 0.4) points in the randomized acupuncture group and by 14.6 (SE, 0.3) to 75.9 (SE, 0.2) points in the nonrandomized acupuncture group; difference = 1.5 points (95 percent CI: –2.4, –0.5); p < 0.003).
Comparing the randomized and nonrandomized acupuncture groups (table 2) for the other outcome parameters after 3 months revealed that the effect of acupuncture was more pronounced in nonrandomized patients with regard to back function loss, back pain, and physical quality of life, whereas mental quality of life was similar in both groups. The proportion of responders was 53.0 percent in the nonrandomized acupuncture group and 52.6 percent in the randomized acupuncture group (p = 0.75).
Factors affecting 3-month back function or pain improvement scores
After adjustment for all other variables, back function loss was significantly more reduced among men, younger patients, patients with more education (>10 years), patients with reduced baseline back function or less back pain, patients with higher baseline physical or mental quality of life, and (regardless of whether the patient received acupuncture) patients whose treating physician had greater experience in acupuncture treatment, as measured by the percentage of acupuncture treatments performed as part of daily clinical practice. Back pain reduction was significantly more pronounced among women, patients with more education, younger patients, patients with higher baseline back pain, patients with a higher baseline physical or mental quality of life, and patients whose treating physician had greater experience in acupuncture treatment.
After inclusion of these baseline variables, the back function loss or back pain differences between the randomized and nonrandomized acupuncture patients disappeared. In other words, the selection due to the randomization requirement could be completely explained by the model. However, three acupuncture effect modifiers could be identified: The acupuncture effects on back function as well as on back pain were more pronounced in patients with worse initial back function (p < 0.001) and younger patients (p < 0.001). Furthermore, the acupuncture effect on back function was higher in patients with more than 10 years of schooling (p = 0.01). The physician's acupuncture qualifications (hours of training, years of experience) had no significant influence on the effect of the treatment.
Durability of acupuncture effects over 6 months
The 6-month follow-up results in the treatment groups are shown in table 2. The 6-month effects in the randomized and nonrandomized acupuncture groups were only slightly lower than they had been at 3 months. In the randomized acupuncture group, the 6-month response rate was 50.0 percent. In the nonrandomized acupuncture group, the response rate was 52.8 percent.
Delayed acupuncture
Of the 1,390 control patients included in the study, 1,205 (87 percent) received delayed acupuncture. Following delayed acupuncture, the improvement in back function loss seen in control patients almost equaled that observed in patients who had been randomized to receive immediate acupuncture therapy (table 2). However, immediate acupuncture was significantly superior to delayed acupuncture with regard to back function loss and the 6-month response rate (50.0 percent vs. 45.5 percent; p = 0.02). In contrast, back pain reduction was not significantly different between the groups.
Side effects
In total, 6 percent of patients (n = 646) reported experiencing side effects after acupuncture; the total number of side effects was 767 (54 percent of patients had minor local bleeding or hematoma, 17 percent had pain (e.g., needling pain), 8 percent had vegetative symptoms, and 21 percent had other side effects). No life-threatening side effects were reported.
Economic analyses
Data on QALYs were available for 2,388 of the 2,841 randomized patients (84 percent; 1,231 acupuncture, 1,157 control). As a result, 2,388 patients were included in the economic analysis.
From baseline to 3 months, we observed significant differences in overall and diagnosis-specific costs between the acupuncture and control groups (€1,062.46 (SD, 1,539.74) vs. €782.36 (SD, 1,728.80) (p < 0.001) and €557.15 (SD, 872.94) vs. €251.91 (SD, 1,065.41) (p < 0.001), respectively). The mean difference between the two treatment groups (€280.10 (95 percent CI: 148.42, 411.78) vs. €305.24 (95 percent CI: 226.79, 383.68)) was essentially due to the costs of acupuncture (€366.95 (SD, 84.90)) in the acupuncture group, whereas no significant differences were observed for other cost components.
Table 3 shows QALY utility values at baseline and after 3 months. There were no significant differences between the two randomized groups at baseline. After 3 months, QALY utility values were higher in the acupuncture group than in the control group (0.65 QALYs (SD, 0.10) vs. 0.62 QALYs (SD, 0.10); p < 0.001).
Time point . | Acupuncture group . | . | Control group . | . | p value† . | ||
---|---|---|---|---|---|---|---|
. | Mean . | SD* . | Mean . | SD . | . | ||
At baseline (α) | 0.60 | 0.11 | 0.61 | 0.11 | 0.455 | ||
At 3 months (β) | 0.69 | 0.12 | 0.63 | 0.12 | <0.001 | ||
Over duration of study: (α – β)/2 | 0.65 | 0.10 | 0.62 | 0.10 | <0.001 |
Time point . | Acupuncture group . | . | Control group . | . | p value† . | ||
---|---|---|---|---|---|---|---|
. | Mean . | SD* . | Mean . | SD . | . | ||
At baseline (α) | 0.60 | 0.11 | 0.61 | 0.11 | 0.455 | ||
At 3 months (β) | 0.69 | 0.12 | 0.63 | 0.12 | <0.001 | ||
Over duration of study: (α – β)/2 | 0.65 | 0.10 | 0.62 | 0.10 | <0.001 |
QALY, quality-adjusted life years; SD, standard deviation.
Two-sided t test.
Time point . | Acupuncture group . | . | Control group . | . | p value† . | ||
---|---|---|---|---|---|---|---|
. | Mean . | SD* . | Mean . | SD . | . | ||
At baseline (α) | 0.60 | 0.11 | 0.61 | 0.11 | 0.455 | ||
At 3 months (β) | 0.69 | 0.12 | 0.63 | 0.12 | <0.001 | ||
Over duration of study: (α – β)/2 | 0.65 | 0.10 | 0.62 | 0.10 | <0.001 |
Time point . | Acupuncture group . | . | Control group . | . | p value† . | ||
---|---|---|---|---|---|---|---|
. | Mean . | SD* . | Mean . | SD . | . | ||
At baseline (α) | 0.60 | 0.11 | 0.61 | 0.11 | 0.455 | ||
At 3 months (β) | 0.69 | 0.12 | 0.63 | 0.12 | <0.001 | ||
Over duration of study: (α – β)/2 | 0.65 | 0.10 | 0.62 | 0.10 | <0.001 |
QALY, quality-adjusted life years; SD, standard deviation.
Two-sided t test.
The incremental cost-effectiveness ratios were estimated to be €10,526 per QALY gained (overall cost perspective) and €11,470 per QALY gained (diagnosis-specific cost perspective). Bootstrapping of the original sample showed that acupuncture in addition to routine care was more effective and more costly than routine care alone (figure 3). The net benefit for a benchmark of €50,000 was €1,050, and the probability that acupuncture was cost-effective was close to 100 percent (figure 4).
DISCUSSION
Patients with chronic low back pain treated with acupuncture in addition to routine care showed significant improvements in symptoms and quality of life compared with patients who received routine care alone. Acupuncture plus routine care was associated with higher costs but was estimated to be cost-effective. In patients who consented to randomization, treatment outcomes after acupuncture were similar to those seen in patients who declined randomization. All of the differences observed can be explained by differences at baseline.
The present study is by far the largest randomized trial of acupuncture in patients with chronic low back pain to date, including 12 percent of physicians specializing in acupuncture and a full 3 percent of all primary care physicians in Germany. We took a pragmatic approach, aiming to evaluate acupuncture in a manner that would reflect as closely as possible the conditions of daily medical practice and maximize external validity. The additional inclusion of patients who declined randomization allowed us to investigate any potential selection effects. Although the study had high follow-up rates, we nevertheless used conservative methods to deal with missing data.
Obviously, such an approach also has its methodological limitations. In this study, neither providers nor patients were blinded to treatment. Therefore, a bias due to unblinding cannot be ruled out. To minimize social acceptability bias, all questionnaires were sent directly to and from the coordinating research institute. The numbers of patients who used analgesic agents during the study were similar in the two randomized groups. Because both the specifics of acupuncture treatment and the specifics of any cointerventions were left to the discretion of the physicians, the treatment regimens in our study were highly variable. Moreover, inclusion criteria were broad, which resulted in a heterogeneous patient sample and possibly some diagnostic misclassification. While these issues might be considered limitations from an experimental perspective, the study design was chosen to reflect general medical practice. Another limitation of our study was that it contained comparative data for only 3 months.
Patient self-selection in randomized studies of complementary and alternative medical treatments could be a relevant problem (24). Although a variety of study designs have been recommended for including both randomized and nonrandomized patients, few studies have actually employed them to date (25). In our investigation, approximately three out of four eligible patients refused randomization, in spite of a minor financial incentive and the seemingly slight disadvantage of having a 50 percent chance of a 3-month delay before starting acupuncture treatment (following an average disease duration of 6.3 years). Although differences in baseline characteristics and treatment outcomes between randomized and nonrandomized patients were small in absolute numbers, our findings indicate that randomization was associated with some selection. This pragmatic study included a large sample of “normal” patients with low back pain in Germany. The patients received acupuncture from physicians who also offered other treatments, including conventional medicine. As a result, our study may have been less subject to selection bias than smaller experimental studies of acupuncture. Therefore, the use of study designs that also include nonrandomized patients appears to be desirable.
It is notable, however, that the benefits of treatment were similar in the randomized and nonrandomized acupuncture groups after adjustment for baseline differences. This suggests that the results of randomized trials can be representative for routine medical care situations, at least in large pragmatic studies. This finding is supported by a review which found that randomized controlled trials and observational studies of acupuncture had comparable results (26).
In both randomized and nonrandomized patients, the improvements seen in back function were clinically relevant (14). An important finding of our study is that the improvements seen immediately after 3 months of treatment continued for at least another 3 months.
Our finding that the formal qualifications of the physician and his/her number of years of acupuncture experience had no significant influence on treatment outcome could be interpreted as a further indication that formal acupuncture training plays only a limited role with regard to treatment effect. However, these results should be interpreted with caution, because the indicators in the present study may not adequately reflect the quality of treatment offered by individual physicians. In general, our regression analyses identified only three variables that predicted treatment outcome, including younger age, more severe complaints, and more than 10 years of schooling.
Our study provides further evidence that acupuncture is a safe intervention. This is in agreement with large, previously published surveys (27, 28). When interpreting these findings, however, one must keep in mind that all acupuncture in this study was administered by physicians.
Acupuncture is a relatively resource-intensive intervention because of the time involved for physicians and patients alike. One randomized trial, a United Kingdom study of acupuncture in the treatment of chronic headache, has included a methodologically sound analysis of cost-effectiveness (23). Those authors concluded that acupuncture is relatively cost-effective in comparison with a number of other interventions provided in the United Kingdom. Our study showed that acupuncture was associated with additional costs but was cost-effective according to international threshold values (22, 29). These results are comparable to the findings of Thomas et al. (30), who calculated a cost-effectiveness ratio of approximately €6,500 for acupuncture treatment of low back pain in the United Kingdom. Although a number of studies have claimed to investigate the cost-effectiveness of other treatment options for patients with chronic low back pain (31–34), no incremental cost-effectiveness ratios have been published to date.
In conclusion, our study showed that acupuncture, in addition to routine care, resulted in a clinically relevant benefit and was cost-effective among patients with chronic low back pain from primary care practices in Germany. Thus, acupuncture should be considered a viable option in the management of patients with chronic low back pain.
This study was funded by a number of German social health insurance funds, including Techniker Krankenkasse BKK Aktiv, Betriebskrankenkasse der Allianz Gesellschaften, Bertelsmann BKK, Bosch BKK, BKK BMW, DaimlerChrysler BKK, BKK Deutsche Bank, Ford Betriebskrankenkasse, BKK Hoechst, HypoVereinsbank Betriebskrankenkasse, Siemens-Betriebskrankenkasse, Handelskrankenkasse, and Innungskrankenkasse Hamburg.
The authors thank Iris Bartsch and Beatrice Eden for data acquisition, the members of the advisory board (Dr. Konrad Beyer, Dr. Josef Hummelsberger, Hardy Müller, Dr. Albrecht Molsberger, Dr. Helmut Rüdinger, Dr. Wolfram Stör, and Dr. Gabriel Stux) for helpful advice, and all participating physicians.
Dr. Bodo Liecker is an employee of Techniker Krankenkasse (Hamburg, Germany), which provided financial support for this study.
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