Acupuncture is a widespread form of complementary

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1 ORIGINAL ARTICLE Acupuncture for Chronic Low Back Pain in Routine Care A Multicenter Observational Study Wolfgang Weidenhammer, PhD,* Klaus Linde, MD,* Andrea Streng, PhD,* Andrea Hoppe, MD,* and Dieter Melchart, MD*w Objective: To investigate patient characteristics and outcomes after undergoing acupuncture treatment for chronic low back pain (clbp) in Germany and to analyze chronification, pain grading, and depression as predictors for treatment outcomes. Patients and Methods: Patients with clbp (ICD-10 diagnoses M54.4 or M54.5) who underwent acupuncture therapy (mean number of sessions 8.7 ± 2.9) within the framework of a reimbursement and research program sponsored by German statutory sickness funds were included in an observational study. Patients were asked to complete detailed questionnaires that included questions on intensity and frequency of pain and instruments measuring functional ability, depression, and quality of life (SF-36) before and after treatment and 6 months after beginning acupuncture. Participating physicians assessed pain chronification in patients. Results: A total of 2564 patients (mean age 57.7 ± 14.0 y, 78.7% female), who were treated by 1607 physicians, were included in the main analysis. After 6 months (6-mo follow-up), 45.5% of patients demonstrated clinically significant improvements in their functional ability scores. The mean number of days with pain was decreased by half (from 21 to 10 d/mo). Employed patients (employed patient subgroup analysis) reported a 30% decrease from baseline in days of work lost. In all, 8.1% of patients reported adverse events, the majority of which were minor. Subgroup analyses focusing on pain severity, stage of chronification, and depression revealed statistically significant relationships both to baseline measures and to reduction of pain after acupuncture. Received for publication July 15, 2005; accepted September 17, From the *Department of Internal Medicine II, Center for Complementary Medicine Research, Technische Universität Mu nchen, Germany; and wdivision of Complementary Medicine, Department of Internal Medicine, University Hospital Zurich, Switzerland. The research program on acupuncture is funded by the following German statutory sickness funds: Deutsche Angestellten- Krankenkasse (DAK), Hamburg; Barmer Ersatzkasse (BEK), Wuppertal; Kaufmännische Krankenkasse (KKH), Hannover; Hamburg-Mu nchener Krankenkasse (HaMü), Hamburg; Hanseatische Krankenkasse (HEK), Hamburg; Gmu nder Ersatzkasse (GEK), Schwäbisch Gmu nd; HZK Krankenkasse fu r Bau- und Holzberufe, Hamburg; Bru hler Ersatzkasse, Solingen; Krankenkasse Eintracht Heusenstamm (KEH), Heusenstamm; Buchdrucker Krankenkasse (BK), Hannover. Reprints: Wolfgang Weidenhammer, PhD, Kaiserstr. 9, Munich, Germany ( Wolfgang.Weidenhammer@lrz.tu-muenchen.de). Copyright r 2007 by Lippincott Williams & Wilkins Conclusions: Acupuncture treatment is associated with clinically relevant improvements in patients suffering from clbp of varying degrees of chronification and/or severity. Key Words: acupuncture, chronic low back pain, depression, chronification of pain, observational study (Clin J Pain 2007;23: ) Acupuncture is a widespread form of complementary medicine. 1,2 Low back pain is one of the leading indications for acupuncture. 3 Regarding chronic pain, results from randomized trials indicate that acupuncture is superior to no treatment or sham therapy for shortterm relief of pain and functional improvement. 4 6 Keeping in mind that there are no evidence-based guidelines for chronic low back pain (clbp), 7 there is no evidence that acupuncture is more effective than conventional standard treatment. However, a large study which was recently completed 8 indicates that acupuncture is superior to standard treatment in patients with clbp. 9 Although findings from such randomized trials can help answer the efficacy question, they cannot provide conclusive results regarding the benefits of acupuncture in the routine care setting. Throughout the 1990s, German statutory sickness funds (which cover about 90% of the population) offered reimbursement for acupuncture on an informal basis. Under increasing pressure to budget health care costs, the German Federal Committee of Physicians and Statutory Sickness Funds decided in October 2000 that the scientific evidence supporting acupuncture was insufficient to justify routine reimbursement. However, it allowed the reimbursement of acupuncture treatment for a limited period of time for a group of conditions where the evidence was considered promising (chronic forms of low back pain, osteoarthritic pain, and headaches) under the precondition that effectiveness be evaluated. To this end, a research program including both randomized trials and a large scale observational study was initiated. 10 Between August 2001 and July 2003, about half a million patients with the above-mentioned pain conditions and 10,000 physicians participated in this project. The conditions for participation were that (1) the physician be accredited for the program (major inclusion criteria: at least 140 h acupuncture training, license to provide medical 128 Clin J Pain Volume 23, Number 2, February 2007

2 Clin J Pain Volume 23, Number 2, February 2007 Acupuncture for Back Pain care within the statutory sickness fund system) and (2) documentation of at least basic information on characteristics, treatment, and outcomes by the physician. A total of about 227,000 patients with clbp as their primary indication for acupuncture were documented. 11 A random sample of these patients was included in an observational study of which we report the results here. The objectives of this study in routine care were to investigate (1) which patients are undergoing acupuncture treatment, (2) whether pain frequency, pain induced disability, and quality of life change after treatment, and (3) how chronification, pain severity, and depression are associated with treatment outcome. PATIENTS AND METHODS To avoid major selection effects and minimize workload, physicians were asked to recruit the first patients, up to a maximum of 6, who had been born in the month randomly assigned to the physician by the coordinating study center. The general inclusion criteria were: age of at least 18 years, knowledge of German and the ability to understand and fill in questionnaires. The following preconditions also had to be met: diagnosis either of lumbago with sciatica (ICD-10: M54.4) or low back pain (ICD-10: M54.5), complaints lasting more than 6 months, no indication for other diseases in the context of back pain, and no acupuncture treatment in the previous 6 months. Acupuncture (insertion of sterile single-use needles at classic acupuncture points) could be provided for up to a maximum of 15 treatment sessions. However, after 6 and 10 sessions, physicians had to provide reasons why further sessions were deemed necessary. The sessions had to be at least 30 minutes in duration. All other aspects of treatment were at the discretion of the treating physicians. Other treatments (medication, physiotherapy, etc) could be prescribed or recommended as needed. Physicians were asked to document details of patient history and the treatments performed and prescribed. They were also asked to complete a scoring form to assess pain chronification [Mainz Pain Staging System (MPSS) 12 ]. The MPSS includes 12 items representing 4 axes (temporal and spatial aspects of pain, drug intake and previous drug withdrawal treatments, and utilization of the health care system). Responses are converted into points using a defined scale and are then used to determine a final classification of I, II, or III, indicating increasing stages of chronification. Patients completed a modified version of the Pain Questionnaire of the German Society for the Study of Pain (DGSS) before the first acupuncture session, after the last session, and 6 months after the first session. It included the following validated instruments: (1) the German version of the Pain Disability Index (PDI), 13 (2) a scale for assessing sensory and affective aspects of pain [Pain Perception Scale (SES)], 14 (3) the German version of the Center for Epidemiological Studies Depression Scale (ADS), 15 and (4) the German version of the SF-36 to assess health-related quality of life. 16 Furthermore, it included numerical rating scales for pain intensity and questions on patient characteristics as well as a question on the number of days with pain and analgesics used during the last 4 weeks. Additionally, patients answered questions on side effects due to acupuncture, made a global assessment of treatment efficacy, and completed a version of the German Hannover Functional Ability Questionnaire (HFAQ), 17 regarding back pain. The HFAQ is a well-validated instrument assessing back function on a scale from 0 to 100 points (100 = perfect back function). All handling of the questionnaires was done by the treating physician and the study center received only anonymous data. Patients were categorized (1) into 3 subgroups according to their stage of chronification (according to MPSS) and (2) into 4 subgroups based on the severity of their chronic pain (according to Von Korff et al 18 ). The severity of chronic pain was determined according to pain intensity and degree of disability using a subset of items of the DGSS Pain Questionnaire and the PDI. Using simple scoring rules, 4 hierarchical classes (subgroups) were created (grade 1: low disability and intensity; grade 2: low disability and high intensity; grade 3: high disability, moderately limiting; and grade 4: high disability, severely limiting). A third subgroup category referred to the extent of depressive symptoms. A total score of more than 23 points in the ADS questionnaire was defined as the cut-off point for depression. 15 The study was not intended to be a confirmatory analysis requiring a single primary result. Instead, variables of major interest were predefined to build a comprehensive profile of outcomes ( quality profile ), for example back function, number of days with pain, and with use of pain medication within the previous 4 weeks, the average intensity of pain on the numerical rating scale during the last 4 weeks, the PDI, perception of pain, depressive symptoms, and quality of life. Descriptive analyses were performed for all data using SPSS software (version 11.5, SPSS Corp, Chicago, IL). Changes from premeasures to postmeasures were presented as mean differences with the 95% confidence interval as an indication of their precision. To estimate the effect sizes for these differences, standardized response means were calculated dividing the mean difference by its standard deviation (SD). 19 Testing for differences between subgroups was performed by w 2 test and by analysis of variance. Multiple linear regression models (stepwise inclusion) were performed to analyze correlations of predictors with treatment outcomes as dependent variables. Because of the exploratory character of the analyses, we did not adjust for multiple testing. To investigate the possible impact of selection for patients in the analysis on treatment outcome, a comparison of basic data with those patients excluded from the analysis was carried out. Furthermore, the effects of different methods for replacing missing data (by last value carried forward or by baseline value) were demonstrated using essential outcome measures. r 2007 Lippincott Williams & Wilkins 129

3 Weidenhammer et al Clin J Pain Volume 23, Number 2, February 2007 All patients were informed about the study preconditions and methods and had to provide written consent. The program was approved by all responsible ethical review boards (regional ethics committees of the German Medical Association). RESULTS Patients A total of 4032 patients were included in the study. A complete set of questionnaires was available for 2564 patients (63.6%) that form the basis for subsequent analyses (Fig. 1). Compared with those patients excluded because of incomplete data sets, there were no statistically significant differences concerning age, sex, frequency of concomitant diseases, or chronification of pain (Table 1). However, the level of education and the rate of employment were lower (P<0.05) in patients with complete documentation. The 2564 patients included in the analysis were treated by 1607 physicians. In all, 47.4% of the physicians were general practitioners, 30.7% were orthopedists, and other diverse disciplines were represented by 22.0%. In addition to the mandatory basic qualification, 31% of the physicians had 350 hours of training in acupuncture. Patient characteristics are summarized in Table 1. Owing to single item missing, the MPSS of chronification could be analyzed in only 73% of the patients. Of these, 38.5% were graded stage I, 48.0% stage II, and 13.5% stage III, the highest stage of chronification. The distribution of chronic pain severity covered the entire range of grades, with 19.7% of patients considered grade 1, 35.8% grade 2, 26.4% grade 3, and 18.1% grade 4. Grades 3 and 4 represent a high degree of pain-induced disability. With respect to the ADS criterion, 39.7% of all Data available: 274 M,P1** Basic sample n=4,880 patients* screened for inclusion 4, General inclusion criteria not fulfilled 4, Specific inclusion criteria notfulfilled 4,032 patients included in study 1,114 M,P1,P2** 341 additional indication for acupuncture 80 2,564 patients M,P1,P3** M,P1,P2,P3** included in main analysis FIGURE 1. Flow chart of the number of patients with low back pain for documentation and statistical analysis. *Physician s questionnaire plus patient s questionnaire before acupuncture available at least; **M = physician s questionnaire; P1 = patient questionnaire before acupuncture; P2 = after acupuncture; P3 = 6 months after start of acupuncture therapy. patients had to be classified as depressive. Thirty percent of the patients already had experience with acupuncture. Before the study, 18% of patients had received acupuncture because of their low back pain and 12% because of other diseases. Treatment The mean number of acupuncture sessions was 8.7 (SD 2.9; Table 2). The median duration of the treatment cycle was 48 days. In 25.1% of patients, physicians prescribed conventional drugs for the treatment of acute pain and in 6.0% for interval therapy. Herbal medicines were prescribed in 4.8% and homeopathic remedies in 4.1%. Neural therapy or related therapies were each used in about 13%. Physiotherapy was recommended to 24.6% of patients, relaxation techniques to 12.7%, physical training in general to 22.4%, and nutritional advice was given to 9.2%. Summarizing all multiple responses, 39% of all patients did not have any single form of concomitant treatment documented. Basic treatment was prescribed in 32.3% of patients, treatment for acute pain only was prescribed in 7.9%, and 21.1% of patients received a combination of both. Treatment Outcomes After completion of acupuncture and 6 months after inclusion in the study, patients reported markedly improved status for all relevant outcome measures. The HFAQ functional ability score improved, after completion of the acupuncture treatment cycle, by an average of 9.4 points (from a mean value of 53.7 before acupuncture) (Table 3). Six months after the start of the treatment the score ranged even higher, with an average improvement of 11.3 points. The corresponding effect sizes in terms of standardized response means were 0.58 and 0.61, respectively. A clinically relevant improvement of 12 points or more 15 was seen in 39.4% of the patients immediately after completing the acupuncture cycle and in 45.5% of the patients by the time of the 6 months query. The mean number of days with pain within the previous 4 weeks was reduced from 20.9 (SD 8.7) to 10.5 days between baseline and 6 months after starting treatment. This represents an effect size of The mean number of days requiring use of pain medication was also reduced by about 50%. However, because of a higher level of variance, the effect size (0.47) was markedly smaller. For further results of outcome measures see Table 3. After completion of acupuncture, 54.4% of patients judged the global effects of treatment to have been good or very good; 30.7% rated the global effects as moderate; and 14.8% considered the effects slight or insufficient. Six months after starting acupuncture, 47.4% of patients rated the success of the treatment as very good or good, 31.6% as moderate, and 21.0% as slight or insufficient. An additional analysis showed that the assessment at the end of treatment by patients with complete documentation was not significantly different from that of patients who discontinued documentation (excluded from main analysis). 130 r 2007 Lippincott Williams & Wilkins

4 Clin J Pain Volume 23, Number 2, February 2007 Acupuncture for Back Pain TABLE 1. Basic Patient Characteristics for the Sample in Analysis (n = 2564) Compared With Patients Excluded From Analysis (n = 1468) Testing for Differences Patients in Analysis Patients Excluded Between Groups n = 2564 n = 1468 P Age (y) mean (SD) 57.7 (14.0) 56.9 (14.4) r40 y 13.8% 14.9% 41 to 60 y 39.2% 41.3% >60 y 47.0% 43.9% Sex: female 78.7% 77.2% Education >10 y school 13.6% 16.1% Employed 41.5% 45.4% Single household 24.2% 25.3% Concomitant diseases 59.2% 56.7% Pain since more than 10 y 34.3% 32.2% MPSS of chronification Stage I = low 38.5% 38.6% Stage II = medium 48.0% 47.5% Stage III = high 13.5% 13.9% Sensitivity analyses, which included all patients (n = 4032), revealed only minor changes in improvement with respect to pain intensity or functional ability when missing 6-month follow-up data were replaced by the last value carried forward method. The changes in response were much larger when missing values were replaced by baseline scores (mean changes diminish from 2.1 to 1.4 for pain intensity and from 11.3 to 6.9 for functional ability). According to the patients, their use of nonmedical services decreased from an average of 3.3 (SD 8.2) visits during the 6 months before acupuncture to 2.2 (SD 7.1) visits for the 6 months after starting acupuncture. For the TABLE 2. Description of Treatment for the Patients With Low Back Pain (n = 2564 Patients) No. acupuncture sessions Mean (SD) 8.7 (2.9) r6 34.8% 7 to % >10 9.2% Concomitant treatment No treatment specified 38.8% Only basic 32.3% Only acute 7.9% Additional treatment prescribed Additional treatment recommended Both 21.1% Conventional drugs for 25.1% acute treatment Conventional drugs for 6.0% basic treatment Herbal drugs 4.8% Homeopathy 4.1% Manual therapy 13.3% Neural therapy 12.6% Physical exercises 12.4% Food therapy 4.3% Other 3.2% Physiotherapy 24.6% Relaxation 12.7% Physical training 22.4% Nutrition 9.2% Other 1.4% subgroup of employed patients (n = 1039), the mean number of days off work owing to low back pain decreased from 11.6 (SD 29.9) to 7.0 (SD 23.5) over the 6-month observation period. Patients with no days off work were assigned a value of 0. For unemployed patients (n = 1466), the number of days with pain-related handicaps in daily life were estimated. This parameter showed a reduction from 36.0 (SD 54.0) days per 6 months on average before acupuncture to 18.1 (SD 34.4) days for the 6-month period starting with acupuncture therapy. Side effects from acupuncture were reported by 8.1% of the patients; about 20% of these considered the side effects to be truly bothersome. Physicians documented adverse reactions in 8.2% of patients, most frequently minor local bleeding or hematoma (4.7%) and needling pain (3.7%). No life-threatening side effects were reported. Associations With Depression, Chronification, and Severity of Pain Chronification of pain, severity of pain, and depression were all shown to have statistically significant associations with the majority of treatment outcomes. However, the standardized weights from regression analysis were small, and the multiple correlations of these predictors with the change scores hardly exceeded a level of Differences in results of short or longer-term treatment effects were incidental. The following examples illustrate in detail the impact of the predictors on baseline values and on changes after treatment. Functional ability was clearly correlated with the severity of chronic pain. The mean HFAQ-scores proved decrease linearly as the grade of pain severity increased (Fig. 2). Treatment effects were greatest in patients with grade 3 (high disability, moderately limiting) and smallest in patients with grade 1 (low disability with low pain r 2007 Lippincott Williams & Wilkins 131

5 Weidenhammer et al Clin J Pain Volume 23, Number 2, February 2007 TABLE 3. Means and SD for Outcomes Before Acupuncture, After Acupuncture and 6 mo after Beginning of Acupuncture Treatment; Mean Differences (With 95% Confidence Interval) and Effect Sizes (Standardized Response Means) Related to Baseline Before Acupuncture After Acupuncture 6 mo After Difference Before/After Difference Before/6 mo After Mean (SD) Mean (SD) Mean (SD) Mean (95% CI) SRM* Mean (95% CI) SRM* Disability HFAQ functional ability (n = 2203) 53.7 (20.8) 63.1 (22.2) 65.0 (22.7) 9.4 (8.7 to 10.1) (10.6 to 12.1) PDI pain disability (n = 2149) 28.8 (14.5) 19.1 (14.9) 17.5 (15.3) 9.7 ( 10.2 to 9.1) ( 12.0 to 10.7) Pain Average pain intensity (n = 2402) 5.6 (1.9) 3.6 (2.2) 3.5 (2.3) 2.0 ( 2.1 to 1.9) ( 2.2 to 2.0) Days with painw (n = 1935) 20.9 (8.7) na 10.5 (10.3) na 10.4 ( 10.9 to 9.9) Days with analgesicsw (n = 2241) 9.7 (10.6) na 5.0 (8.6) na 4.7 ( 5.1 to 4.2) SES pain perception affective (n = 2130) 31.4 (10.0) 25.3 (10.1) 24.0 (10.2) 6.1 ( 6.5 to 5.8) ( 7.8 to 7.0) SES pain perception sensory (n = 2094) 17.9 (6.4) 15.5 (5.8) 15.1 (6.0) 2.5 ( 2.7 to 2.2) ( 3.1 to 2.6) Depression, Quality of Life ADS depressionz (n = 1679) 55.7 (9.4) 50.1 (10.2) 50.0 (10.8) 5.6 ( 6.0 to 5.2) ( 6.2 to 5.3) SF-36 physical healthz (n = 2121) 31.3 (8.2) 37.7 (10.4) 39.1 (10.8) 6.4 (6.0 to 6.8) (7.4 to 8.2) SF-36 mental healthz (n = 2121) 45.5 (12.2) 49.6 (11.0) 48.8 (11.4) 4.1 (3.7 to 4.5) (2.8 to 3.7) Differing sample sizes are due to single items missing; concerning the ADS Depression scale more patients had to be excluded from analysis because of inconsistent response patterns. *SRM = standardized response mean (mean difference/sd of difference). wwithin the past 4 wk. zresults are presented as standard scores using a norm based T-scale with mean = 50 and SD = 10. CI indicates confidence interval; na, not applicable. intensity). The hypothesis of equal before-after differences in patient subgroups according to their severity grade had to be rejected (P<0.001). Mean baseline scores ranged from 68.6 (SD 17.5) for patients with grade 1 to 38.3 (SD 17.5) for patients with grade 4 (P<0.001). A similar relationship could be found between chronification and function as measured by the PDI. Again, there were statistically significant differences in baseline values (P<0.001), representing a range of mean baseline scores from 26.7 (SD 14.0) in stage I to 35.8 (SD 14.5) in stage III. However, the magnitude of improvement was similar in all 3 subgroups of patients (no statistically significant differences between groups). Before treatment, depressed patients showed an average intensity of pain of 6.3 (SD 1.9) on a 0-10 point rating scale, whereas patients without depression reported a lower mean value of 5.2 (SD 1.8) (P<0.001). After acupuncture, in both subgroups with and without depression, pain intensity decreased by an average 2.2 and 2.0 points, in the subgroups with and without depression, respectively. These changes lasted for 6 months after starting acupuncture. There were also clear differences in both groups concerning health-related quality of life. Patients without depression showed a significantly higher improvement (P<0.01) in physical health (SF-36 Physical Component Score) than patients with depression (Fig. 3). Concerning mental health, the results were just the opposite. While patients with Functional Ability, mean +/- 1 sd low disability/intensity (1) low disability/ high intensity (2) high disability, moderately limiting (3) high disability, severely limiting (4) FIGURE 2. Mean functional ability (HFAQ; 0 = minimal to 100 = perfect back function) ± SD before acupuncture (dark gray bars), after acupuncture (gray bars) and 6 months after onset of acupuncture (light bars) stratified by chronic pain severity. 132 r 2007 Lippincott Williams & Wilkins

6 Clin J Pain Volume 23, Number 2, February 2007 Acupuncture for Back Pain FIGURE 3. Mean quality of life (SF-36 component scores: physical health = left side and mental health = right side; 50 ± 10 = range of population based normal quality of life with higher values corresponding to better quality of life) ± SD before, after acupuncture and 6 months after (dark bars = without depression, light bars = with depression). Physical health, mean +/- 1 sd before acupuncture after acupuncture 6 months after Mental health, mean +/- 1 sd before acupuncture after acupuncture 6 months after depression who indicated a decreased baseline level of quality of life clearly improved after acupuncture, differences in mean scores of patients without depression varied very little in a small range above the mean level of normal population samples. The percentage of depressed patients was strongly associated with pain severity grading (P<0.001), but there was no statistically significant relationship with chronification. Furthermore, no interactive effect of severity and chronification could be observed with respect to the prevalence of depression. Regardless of the stage of chronification, the rate of depressed patients was higher in patients with a higher severity grading (at severity grade 4 about 60% depressed patients). DISCUSSION The results of this observational study show that a large number of patients with clbp has been treated with acupuncture by physicians within the reimbursement and research program in Germany. Compared with outpatients in routine care, study participants presented a slightly elevated mean age, a higher proportion of females, and a better education level. 20 Patients reported significant benefit both after treatment and after 6 months for a broad range of different outcome measures. The amount of improvement exceeded commonly accepted criteria for clinical importance in treatment for clbp. 21 This is linked to a relevant relief in disease-related complaints being felt by the patients. Reduction in days off work or use of nonmedical services during the 6- month period after starting acupuncture treatment demonstrated a relevant reduction of the economic burden of the condition. Acupuncture was well tolerated by the patients. Clear strengths of our study are the large sample size and its external validity. This assures sufficient power when comparing the different subgroups. Because of its minimal interference with routine practice, the findings of the study reflect current practice in Germany, even though defined by the general regulations of the refunding program. The questionnaire used is recommended by the German Society for the Study of Pain for documentation in patients with chronic pain and is widely applied in Germany. 22 The variety of instruments included in the questionnaire allows assessment of different aspects of pain, functionality, and mental health. The observation period of 6 months meets common demands for studies on chronic pain conditions. One important shortcoming of the study is that results might be biased by attrition of the cohort. Change scores between baseline, after treatment and at 6 months, respectively, were derived from our patient sample with a complete set of questionnaires and, hence, may provide an overoptimistic estimate. Patients who terminated acupuncture early and patients who were unsatisfied were less likely to provide all questionnaires. Unfortunately, physicians did not consistently document the reasons why follow-up questionnaires were not available. The reasons that were documented were primarily organizational problems or personal issues (unsuitable dates with the doctor, questionnaire forgotten, unwillingness to fill in one more extensive leaflet). There was, however, nothing that indicated a considerable relationship to unsatisfying treatment results. Regardless, our comparisons of patient characteristics at the different levels of sampling suggest that the degree of overestimation owing to selection bias should be limited. 11 As a consequence, the results of the sensitivity analyses in which all missing data were replaced by baseline values are likely to be r 2007 Lippincott Williams & Wilkins 133

7 Weidenhammer et al Clin J Pain Volume 23, Number 2, February 2007 too conservative and indicate only the theoretical range of true effects. Furthermore, physicians were to select patients with nonspecific forms of low back pain. However, diagnostic procedures excluding specific etiologic factors for back pain could not be standardized or monitored within this trial. Physicians were free to apply, prescribe, and recommend other treatments as our study was intended to reflect routine practice as closely as possible. This led to a high level of cointervention which, of course, might have affected the outcomes. Stages of chronification of pain and severity grading indicated several statistically significant relationships with treatment outcomes. But clinical importance could only be established for chronification with respect to reduced use of analgesics and for pain severity in case of decreased disability or intensity of pain. As a result, acupuncture looks to be similarly useful in clbp with different levels of chronification and severity. Depression proved to be strongly related to an improvement in mental health, and, as a condition of baseline value, with a reduction of depressive symptoms. On the one hand, there is a marked close association between the stage of chronification and depressive disorders. 23 On the other hand, our data indicate a closer relationship between grades of severity of pain and depression. Although affective distress is considered an important predictor for clbp after treatment, 24 we found that patients both with and without suggestive depression scores experienced similar pain relief. The different levels of pain intensity in both groups make it unlikely that the observed improvements were biased by the effect of regression to the mean. Like the ADS, many questionnaires for assessing depression comprise somatic items (eg, sleep disorders, tiredness), which accompany many chronic pain conditions without having a primary psychopathologic meaning. Therefore, our results on prevalence of depressive disorders may overestimate the problem. A study that used standardized diagnostic interview tools found the prevalence of depression among patients with recurring back pain to be 21%. 25 In contrast, we found that 40% of our patients had ADS scores exceeding the critical limit for depressive disorders; another trial on clbp under primary care conditions in Germany reported similar results. 20 Although we believe that our study provides valid and important descriptive data for acupuncture in patients with clbp, it does not offer conclusive evidence regarding the extent to which the observed improvements were caused by acupuncture. As a consequence, we also performed a randomized trial within the research program comparing acupuncture with minimal acupuncture (a sham intervention involving superficial needling at nonacupuncture points) and a waiting list. As in another recently finished large randomized study, 26 acupuncture proved to be clearly superior to the waiting list. 27 Compared to minimal acupuncture, significant differences were found for several secondary outcome measures but not for the predefined main outcome measure (decrease in pain intensity). It is not fully clear why the results of these trials deviate from previous findings. 5,6 However, effects unrelated to correct placement of acupuncture needles such as nonspecific needling effects, expectations, and other placebo effects might contribute considerably to the total clinical outcome. In conclusion, our large pragmatic observational study in routine care in Germany corroborates findings from randomized trials suggesting that patients with clbp benefit from treatment with acupuncture. The benefit seems to be similar in patients with different grades of chronification and severity, and among patients with and without depression. It recommends acupuncture as a serious treatment option for clbp. Further research is needed to elucidate the mechanisms of the effects associated with acupuncture treatment, the cost-benefit relationship, and whether outcomes under conditions of routine care are similar in other health care systems. REFERENCES 1. Ernst E. Prevalence of use of complementary/alternative medicine: a systematic review. Bull World Health Organ. 2000; 78: Fisher P, Ward A. Complementary medicine in Europe. BMJ. 1994;309: Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, : results of a follow-up national survey. JAMA. 1998;280: Smith LA, Oldman AD, McQuay HJ, et al. Teasing apart quality and validity in systematic reviews: an example from acupuncture in chronic neck and back pain. Pain. 2000;86: Manheimer E, White A, Berman B, et al. Meta-analysis: acupuncture for low back pain. Ann Intern Med. 2005;142: Furlan AD, van Tulder M, Cherkin D, et al. Acupuncture and dry-needling for low back pain: an updated systematic review within the framework of the Cochrane collaboration. Spine. 2005; 30: Bogduk N. Management of chronic low back pain. Med J Aust. 2004;180: Haake M, Muller 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: Press release from October 21, geraclong.pdf. 10. Melchart D, Streng A, Reitmayr S, et al. Patient care evaluation programme on acupuncture (PEP-AC) the scientific concept of the German statutory insurance funds model project. Z a rztl Fortbild Qual Gesundh wes. 2004;98: Weidenhammer W, Streng A, Ju rgens S, et al. Structure, realization and data synopsis of an observational study as part of the patient care evaluation programme on acupuncture (PEP-AC) drafted by German statutory insurance institutions. Gesundheitswesen. 2005;67: Gerbershagen HU. Organized pain management state of the art. Internist. 1986;27: Dillmann U, Nilges P, Saile H, et al. Assessing disability in chronic pain patients. Schmerz. 1994;8: Geissner E, Schulte A. The Pain Perception Scale (Die Schmerzempfindungs-Skala SES). Weinheim: Beltz; r 2007 Lippincott Williams & Wilkins

8 Clin J Pain Volume 23, Number 2, February 2007 Acupuncture for Back Pain 15. Hautzinger M, Bailer M. German Version of the Center for Epidemiological Studies Depression Scale CES-D (Allgemeine Depressionsskala ADS). Weinheim: Beltz; Bullinger M, Kirchberger I. SF-36 Health Survey. Go ttingen: Hogrefe; Kohlmann T, Raspe H. Hannover Functional Questionnaire in ambulatory diagnosis of functional disability caused by backache. Rehabilitation. 1996;35: Von Korff M, Ormel J, Keefe FJ, et al. Grading the severity of chronic pain. Pain. 1992;50: Fortin PR, Stucki G, Katz JN. Measuring relevant change: an emerging challenge in rheumatologic clinical trials. Arthritis Rheumat. 1995;38: Lang E, Eisele R, Jankowsky H, et al. Outcome quality of treatment for chronic low back pain under primary care conditions. Schmerz. 2000;14: Hägg O, Fritzell P, Nordwall A. The clinical importance of changes in outcome scores after treatment for chronic low back pain. Eur Spine J. 2003;12: Nagel B, Gerbershagen HU, Lindena G, et al. Development and evaluation of the multidimensional German pain questionnaire. Schmerz. 2002;16: Frettlo h J, Maier C, Gockel H et al. Validation of the German Mainz pain staging system in different pain syndromes. Schmerz. 2003;17: Michaelson P, Sjo lander P, Johansson H. Factors predicting pain reduction in chronic back and neck pain after multimodal treatment. Clin J Pain. 2004;20: McWilliams LA, Goodwin RD, Cox BJ. Depression and anxiety associated with three pain conditions: results from a nationally representative sample. Pain. 2004;111: Becker-Witt C, Jena S, Lo bel S, et al. Effectiveness of acupuncture in 2,807 patients with chronic low back pain in routine care. Focus Altern Complement Therap (FACT). 2003; 8: Brinkhaus B, Witt C, Jena S, et al. Acupuncture in patients with chronic low back pain a randomised controlled trial. Arch Intern Med. 2006;166: r 2007 Lippincott Williams & Wilkins 135