Appropriateness of sham or placebo acupuncture for randomized controlled trials of acupuncture for nonspecific low back pain: a systematic review and meta-analysis

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Journal of Pain Research 2018:11 83–94

Journal of Pain Research

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Appropriateness of sham or placebo acupuncture

for randomized controlled trials of acupuncture

for nonspecific low back pain: a systematic review

and meta-analysis

Yan Xiang1

Jinyuan He2

Rui Li1

1_{Department of Teaching, School of} Acupuncture and Moxibustion and

Tuina, Beijing University of Chinese

Medicine, Beijing, China; 2_Department

of Cardiothoracic Surgery, The Third

Affiliated Hospital of Sun Yat-sen

University, Guangzhou, China

Objectives: To establish whether sham acupuncture (SA) or placebo acupuncture (PA) is more efficacious for reducing low back pain (LBP) than other routine treatments and to discuss whether SA or PA is appropriate for randomized controlled trials of acupuncture for LBP.

Methods: Six databases were searched on 31 May 2017. We included only randomized

con-trolled trials of adults with LBP and lower back myofascial pain syndrome. The studies had at least two control arms: a sham-controlled acupuncture arm and a routine care or waiting list arm (people who did not receive acupuncture until the end of treatment). Trials were combined using meta-analysis methods when the data allowed statistical pooling. Pooled effect sizes were calculated by random effects models.

Results: This review identified 7 trials (1768 participants); all were included in the meta-analysis. We found statistically significant differences in pain reduction post-intervention between SA or PA and routine care or a waiting list, with a standardized mean difference of −0.36 (95% CI −0.54 to −0.18; I2 _statistic=_{16%; participants}=_{624; studies}=_{6) for the Visual Analog Scale and}

−0.35 (95% CI −0.49 to −0.20; I2 _statistic₌_{0%; participants}₌_{736; studies}₌_{1) for the Chronic Pain}

Grade Scale; however, no significant difference was observed between SA or PA and routine care or no treatment for post-intervention function.

Conclusion: Compared with routine care or a waiting list, SA or PA was more efficacious for pain relief post-intervention. Concluding that SA or PA is appropriate for acupuncture research would be premature. Guidelines evaluating SA or PA control methods are needed to determine the specific effect of acupuncture over placebo.

Keywords: acupuncture, alternative medicine, backaches, pain management, placebos, con-trolled clinical trial, lumbago

Introduction

Nonspecific low back pain (LBP) is among the most common health complaints; it is the leading cause of years lived with disability worldwide and sixth in terms

of overall disease burden (disability-adjusted life-years).1_{Although LBP is usually}

a self-limiting and benign disease, a large variety of therapeutic interventions are

available to treat it.2

Acupuncture, based on the concepts of traditional Chinese medicine (TCM), is one of the oldest and most popular complementary or alternative treatment methods. Although it is one of the most commonly used interventions to treat LBP, acupuncture Correspondence: Rui Li

Department of Teaching, School of Acupuncture and Moxibustion and Tuina,

Beijing University of Chinese Medicine, No.11 Bei San Huan Dong Lu, Chaoyang

District, Beijing 100029, China Email [email protected]

Journal name: Journal of Pain Research Article Designation: ORIGINAL RESEARCH Year: 2018

Volume: 11

Running head verso: Xiang et al

Running head recto: Appropriateness of sham or placebo acupuncture for RCTs DOI: http://dx.doi.org/10.2147/JPR.S152743

Journal of Pain Research downloaded from https://www.dovepress.com/ by 118.70.13.36 on 24-Aug-2020

For personal use only.

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Xiang et al

has mixed support. Despite a 2005 Cochrane review that reported the existence of some evidence supporting

acu-puncture for chronic LBP,3_{a conclusion supported by another}

systematic review,4_{the National Institute for Health and Care}

Excellence (NICE) in the UK removed acupuncture from their LBP guidelines in early 2016, citing a lack of evidence

to indicate that it was more effective than sham treatment.5

Sham acupuncture (SA), also called placebo acupunc-ture (PA), performed away from the acupuncacupunc-ture points established by TCM or without stimulation and manipula-tion to avoid eliciting “De Qi” sensamanipula-tions or using a non-penetrating technique, is used as control in scientific studies

to determine the efficacy of acupuncture.6,7_{However, in}

China, wrist-ankle acupuncture and abdomen acupuncture, both with shallow needling, are the primary treatments for LBP. It might be argued that the superficial or minimal acupuncture might stimulate C fibers in the skin to trigger

some kind of analgesic effect.8,9_{Of those sham-controlled}

clinical trials, several of them found no significant differ-ences between real acupuncture and SA/PA in pain relief for LBP.10–14_{As a result, controversy persists regarding whether}

acupuncture for LBP works primarily by the placebo effect. Meanwhile, some investigators argued that using SA/PA as a control is problematic because SA/PA might not meet the

criteria of being physiologically inert.15,16

Regardless, no systematic review and meta-analysis to date has addressed whether SA/PA has effects for LBP. We, therefore, performed a systematic review and meta-analysis of acupuncture for the treatment of LBP to determine whether SA/PA was more efficacious in reducing LBP than routine care and to discuss whether SA/PA is appropriate for use in randomized controlled trials (RCTs) of acupuncture for LBP.

Methods

Criteria for considering studies for this

review

Types of studies

We included only RCTs, which provide the highest level of evidence to assess the effects of interventions. Moreover, the studies had at least two control arms: a sham-controlled acupuncture arm and a routine care or waiting list (people who did not receive acupuncture until the end of treatment) or no treatment arm. Articles published in English or Chinese without region restriction were included.

Types of participants

We included studies which recruited adults (>18 years) with

LBP or myofascial pain syndrome in the lower back. RCTs

that included subjects with LBP caused by specific pathologi-cal entities such as infection, metastatic disease, neoplasm, osteoarthritis, rheumatoid arthritis, inflammatory processes, radicular syndrome, or fractures were excluded. Patients with LBP associated with sciatica as the major symptom, pregnancy, post-partum status, and post-operative LBP were

also excluded. Patients with acute, sub-acute (≤12 weeks),

or chronic LBP (>12 weeks) were included.

Types of interventions

We included studies in which acupuncture points were stimulated by needle insertion (with or without electroacu-puncture), accompanied by a definite sensation of De Qi. The studies in which methods of stimulating acupuncture points by acupressure, transcutaneous electrical nerve stimulation, or infrared light for verum acupuncture were excluded. Bee venom acupuncture and ear acupuncture were excluded. Tri-als comparing two techniques of acupuncture were excluded. Trials assessing the efficacy of acupuncture as an adjunct treatment to other therapies compared to SA/PA as an adjunct treatment to other therapies were included.

Types of outcome measures

RCTs were included if they used at least one of the following two outcome measures considered salient in the field of LBP:

1. Pain intensity (e.g., Visual Analog Scale [VAS]); 2. Back-specific functional status (e.g., Roland–Morris

Disability Questionnaire [RMDQ]).

The primary outcome was pain intensity. The secondary outcome measure was back-specific functional status.

Search methods for identification of

studies

Electronic searches

We searched the following databases:

1. Cochrane Central Register of Controlled Trials (CEN-TRAL; the Cochrane Library, to Issue 5 of 12 May 2017) on 31 May 2017

2. PubMed (1980 to May 2017) on 31 May 2017

3. EMBASE (Ovid SP, 1980 to May 2017) on 31 May 2017 4. China National Knowledge Infrastructure, the Wan Fang

and the Wei Pu databases up to 31 May 2017

Keywords, free words, and MeSH terms including “acupunc-ture” OR “acupuncture therapy” OR “acupuncture points” AND “low back pain” OR “lower back pain” OR “backache” OR “lumbago” were used.

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Dovepress Appropriateness of sham or placebo acupuncture for RCTs Searching other resources

Keywords of the references of all pertinent publications were traced, including systematic reviews and meta-analyses, to identify citations omitted by the electronic search.

Data collection and analysis

Selection of studies

For this review, one author generated the electronic search strategies in the CENTRAL, PubMed, EMBASE, and Chi-nese databases and downloaded the citations. Two authors independently applied the aforementioned inclusion criteria to identify trials. Any disagreements between them were resolved by consensus with a third review author acting as an arbiter. The authors of recent original studies were contacted to obtain more information when needed.

Data extraction and management

Two authors independently extracted data on the study characteristics, study population, duration of symptoms, treatment type, frequency and duration of the intervention, outcome measurements, and type of comparisons. A standard extraction form was used. Discrepancies were reassessed and consensus was reached by discussion. If necessary, a third author reviewed the data to reach consensus.

Assessment of risk of bias in included studies

Two authors independently assessed the risk of bias of each included trial using the criteria recommended in The Cochrane Handbook for Systematic Reviews of Interven-tions.17_{Six domains of bias were assessed: selection bias,}

performance bias, detection (or measurement) bias, attrition bias, reporting bias, and other bias (registered or not, ethics approval obtained or not, participants gave the informed consent or not, etc.). For each study, we scored each criterion as “high risk”, “low risk”, or “unclear”. Any disagreements were resolved by consensus and a third author was consulted if disagreements persisted. We also used the risk of bias assessment of the included trials for grading the quality of the evidence.

Measures of treatment effect

The analyses compared SA/PA to no treatment or routine care. For continuous measures, the use of weighted mean differences was preferred to analyze the results when the outcome measures were identical. Standardized mean dif-ferences (SMD) were used when different instruments were

used for the same outcome measurements.18,19

Unit of analysis time frame

We extracted data from the outcomes measured immediately following the end of the sessions for up to 1 week after the end of the sessions.

Missing data management

When data were missing, attempts were made to obtain information by contacting the study authors.

Assessment of heterogeneity

Random effects models were used for all meta-analyses. This method is recommended by the CBN Group Edito-rial Board because the assumptions underlying the random effects model are better suited to the statistical combination

of trials in this field.20

Assessment of reporting biases

Publication bias was assessed using funnel plots generated using RevMan (version: 5.3.5 [Java 7 64 bit]) Analysis

Software.21_{We used the method of independent visual}

inspection by two review authors. A third review author was consulted in cases of disagreement.

Data synthesis

We entered all quantitative results into RevMan (version:

5.3.5 [Java 7 64 bit]) Analyses Software.21_{A meta-analysis}

was considered when homogeneity existed in terms of population, comparison group, and outcome. The mag-nitude of the effect size was categorized as follows: 0.2 indicates a small effect, 0.5 a moderate effect, and 0.8 a

large effect.22

The GRADE approach was utilized to assess the qual-ity of the evidence. This grading method for each outcome considered risk of bias, inconsistency of results, indirectness

of evidence, imprecision, and publication bias.23

Subgroup analysis and assessment of heterogeneity

Assessments not planned in this review were subgroup or meta-regression analyses and sensitivity analysis.

Results

Description of studies

Results of the search

The flow of studies is illustrated in Figure 1 study flow diagram. In this review, we identified seven trials for

inclusion.10,11,13,14,24

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Included studies

In total, we included 7 trials (1768 participants). Four studies

were conducted in Germany (1139 participants),10,13,24,25_one

was conducted in the USA (323 participants),11_{one was}

con-ducted in Spain (206 participants),14_{and one was conducted}

in China (100 participants).26

Most patients included in these trials had chronic non-specific LBP. The control groups included conventional treatment, standard therapy, routine care, and waiting list.

The type of SA/PA varied among the included trials: four studies used a superficial insertion method at non-

acupuncture points,10,13,24,25_{one used a toothpick in a needle}

guide tube,11_{and one penetrated at nonspecific}

acupunc-ture points that were then puncacupunc-tured following the usual

procedure.14_{The sham needles in the final study differed}

from regular needles in that they had blunt and retractable

tips, although true acupuncture points were treated.26

Details of each included trial are presented in Table 1.

Risk of bias in included studies

Some degree of publication bias was suggested (Figure 2), which may be attributed in part to the small number of studies. A summary of the risk of bias for each article is shown in Figure 3.

Figure 1 Study flow diagram.

Duplicate records found (n=265)

Additional records identified through other sources

(n=20) Records identified through

database searching (n=2930)

Records screened (n=2685)

Full-text articles assessed for eligibility

(n=44)

Full-text articles excluded, with reasons

(n=37) 1. Acupuncture not appropriate (n=19)

Studies included in qualitative synthesis

(n=7)

Included

Eligibility

Screening

Identification

Studies included in quantitative synthesis

(meta-analysis) (n=7)

7. Results not reported (n=3)

6. Conference abstract (n=2)

5. Outcome measures not appropriate (n=2)

4. Absence of no treatment or routine care (n=7) 2. Patients with multiple sclerosis (n=2)

3. Absence of sham treatment (n=2)

Records excluded (n=2641)

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Table 1

Study design and outcome measures

Trials

Number of treatments/ Frequency/Duration per treatment Intervention group (N, Age, Sex) Type of intervention Control group (N, Age, Sex) Type of comparison Duration of pain Duration of intervention Outcome measures Adverse effects

Brinkhaus et

al

10

12 sessions, 30 min per session

a

N

=

73 (18M, 55F) Mean

age

=

58

Minimal acupuncture

N

=

79 (25M, 54F)

Mean age = 59 Waiting list > 6 months 8 weeks

VAS, FFbH-Rscore, PDI score

Reported

Cherkin et

al

11

b

N

=

162 (102M, 60F)

Mean age

=

47

Simulated acupuncture

N

=

161 (97M, 64F)

Mean age = 46 Usual care > 3 months 7 weeks

RMDQ, symptom bothersomeness

Reported

Haake et

al

24

N

=

387 (140M, 247F)

Mean age

=

49

Sham acupuncture

N

=

388 (165M,

223F) Mean age

= 51 Standard therapy > 6 months 6 weeks

Von Korff CPGS, HFAQ

Reported

Leibing et

al

13

N

=

45 (18M, 27F) Mean

age

=

49

Sham acupuncture

N

=

46 (19M, 27F),

Mean age = 48 Control group > 6 months 12 weeks VAS, PDI Reported

Molsberger et al

25 12 sessions, 3 per week,

30 min per session

N

=

61 (33M, 28F) Mean

age

=

50

Sham acupuncture

N

=

60 (28M, 32F),

Mean age = 49 COT alone ≥ 6 weeks 4 weeks VAS No Yuan et al 26

N

=

50 (15M, 35F) Mean

age

=

46

Sham acupuncture

N

=

50 (16M, 34F)

Mean age = 44 Waiting list < 2 weeks 6 weeks VAS, ODI Reported Vas et al 14

N

=

68 (29M, 39F)

Mean age = 44; N = 69

(35M, 34F) Mean age

=

44

Sham acupuncture; placebo acupuncture

N

=

70 (25M, 45F),

Mean age

=

41

Conventional treatment

< 2 weeks 2 weeks VAS, RMDQ No Notes:

aUsually two sessions in each of the first 4 weeks, followed by one session per we

ek in the remaining 4 weeks.

bTwice weekly for 3 weeks and then once weekly for 4 weeks.

Abbreviations: COT, conventional orthopedic therapy; CPGS, Chronic Pain Grade Scale; F, female; FFbH-R, Funktionsfragebogen Hannover-Rücken (back function questionnaire); HFAQ, Hanover Functional Ability Questionnaire; M,

male; ODI, Oswestry Disability Index; PDI, Pain Disability Index; RMDQ, Roland-Morris Disability Questionnaire; VAS, Visual Analog Scale.

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Figure 3 provides an overview of the methodological quality assessment of the included studies. Three of the

tri-als had a low risk of bias.11,14,24_{Two studies had a high risk}

of bias.25,26_{The remaining two studies had an unclear risk of}

bias.10,13_{All studies fully or partially fulfilled the categories}

of allocation concealment, selective outcome, incomplete outcome data, and other sources of bias. The two trials at high risk of bias were deemed as such because of the lack of blinding of participants and personnel.

Effects of interventions

The studies compared SA/PA to routine care or waiting list. Based on the current evidence, SA/PA was clearly more effective than routine care or waiting list for pain relief post-intervention, with an SMD of −0.36 (95% CI −0.54 to −0.18;

I2_statistic=_{16%) in VAS and −0.35 (95% CI −0.49 to −0.20; I}2

statistic=0%) in Chronic Pain Grade Scale (CPGS; Figure 4).

Five of the seven included trials measured functional dis-ability outcomes, with two using the RMDQ, two using the Pain Disability Index (PDI), and one using the Oswestry Dis-ability Index (ODI). No significant difference was observed between SA/PA and routine care or no treatment as measured immediately after the end of the sessions (RMDQ: SMD of

0.11; 95% CI −0.78 to 1.00; I2 _statistic=_{94%; PDI: SMD of}

−0.42; 95% CI −0.90 to 0.05; I2_statistic=_{66%; ODI: SMD}

of −0.30; 95% CI −0.69 to 0.10; Figure 5).

A summary of the findings for the main comparison is presented in Table 2.

Subgroup analysis

We added the subgroup analysis of VAS post-intervention, though we did not plan it in the protocol, because control groups in the included studies contained routine care and waiting list. Thus, we made the subgroup routine care versus waiting list. The results are consistent with pain differences in favor of SA/PA in both the routine care (mean difference [MD] −6.98 [95% CI −12.37, −1.59]) and waiting list sub-groups (MD −13.70 [95% CI −20.32, −7.08]; Figure 6). The total MD and 95% CI were −9.66 (−13.84, −5.84) in favor of SA/PA. A similar finding was shown in chronic LBP sub-group for VAS (Figure 7). But there were no differences found in acute and chronic LBP subgroups for RMDQ (Figure 8).

Discussion

Summary of main results

Seven RCTs comprising a total of 1768 patients were included in this systematic review and meta-analysis. Moderately significant evidence was obtained for the

Figure 2 Funnel plot of comparison between SA/PA and routine care for LBP. Outcome: pain intensity (higher score signifies greater pain).

Abbreviations: CPGS, Chronic Pain Grade Scale; LBP, low back pain; PA, placebo acupuncture; SA, sham acupuncture; SE, standard error; SMD, standardized mean differences; VAS, Visual Analog Scale.

0.5

Subgroups

Pain (VAS) Pain (CPGS)

–2 –1 0 1 2

SMD 0.4

0.3 0.2 0.1

0 SE (SMD)

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Dovepress Appropriateness of sham or placebo acupuncture for RCTs effectiveness of SA/PA for pain intensity as measured at the end of the treatments for LBP management. However, the review demonstrates scant support for the superior effectiveness of SA/PA compared with routine care or waiting list for back-specific functional status at the end of the treatments.

Overall completeness and applicability of

evidence

We did not find a large effect size in the meta-analysis of continuous outcomes for pain intensity. All meta-analyses of continuous outcomes were performed using SMD values because the included trials used different measurement instruments for the outcomes of interest (pain and function). The disadvantage of using SMD values is that clinicians and patients are unlikely to relate to this way of presenting results. No serious adverse events were observed in these trials; the most common adverse event was increased pain after the massage sessions.

Quality of the evidence

In this review, we found two trials with unclear allocation of concealment bias and one trial with unclear selective report-ing bias, suggestreport-ing that some studies may have exaggerated estimates of the intervention effect size compared with large trials. Two trials did not blind participants and personnel, suggesting that blinding patients and health-care providers was the most challenging methodological step in clinical trials of acupuncture, notwithstanding the recently improved methodological quality of the included RCTs.

Figure 3 Summary of risks of bias.

Note: +, yes; -, no; ?, unclear.

Brinkhaus et al10

Random sequence generation (selection bias

)

Allocation concealment (selection bias

)

Blinding of participants and personnel (performance bias

)

Blinding of outcome assessment (detection bias

)

Incomplete outcome data (attrition bias

)

Selective reporting (reporting bias

)

Other bias

Cherkin et al11

Haake et al26

Leibing et al13

Molsberger et al27

Yuan et al28

Vas et al14

Figure 4 Forest plot of comparison between SA/PA and routine care or waiting list for LBP. Outcome: pain intensity – VAS and CPGS.

Abbreviations: CPGS, Chronic Pain Grade Scale; IV, inverse variance; LBP, low back pain; PA, placebo acupuncture; SA, sham acupuncture; Std, standard; VAS, Visual Analog Scale.

Study or subgroup 1.1.1 Pain (VAS)

Brinkhaus et al10 _43.7

32 36 46 33 45

29.8 22 19 27 50.8 70.3

70 40 58 50 62 63

58.6 44 39 58.3 49 49

25.1 17 21 22.5 72.1 72.1

57.1 16.5 361

361 74 39 58 50 30 30 281

10.6% 5.7% 8.8% 7.4% 6.1% 6.2% 44.8%

−0.54 [−0.87, −0.21]

−0.60 [−1.05, −0.15] −0.15 [−0.51, 0.22] −0.49 [−0.89, −0.09] −0.27 [−0.71, 0.17] −0.06 [−0.49, 0.38]

−2 −1 0 1 2

−0.36 [−0.52, −0.20]

55.2%

55.2% −0.35 [−0.49, −0.20]−0.35 [−0.49, −0.20]

343

51 18.7

375

642 100.0% −0.35 [−0.46, −0.24] 718

375

Leibing et al13

Molsberger et al27

Yuan et al28

Vas et al14

Haake et al26

Heterogeneity: c2_=5.97,_df₌₅₍_p_=0.31);_I2_=16%

Test for overall effect: Z=4.36 (p<0.0001)

Heterogeneity: c2_=5.99,_df_{=6 (}_p_=0.42);_I2_=0%

Test for subgroup differences: c2_=0.02,_df_{=1 (}_p_=0.90),_I2_=0%

Heterogeneity: not applicable

Subtotal (95% Cl)

Total (95% Cl) 1.1.2 Pain (CPGS)

Sham

Mean acupuncture Routine care

Sham acupuncture Routine care

Std mean difference Std mean difference

IV, Fixed, 95% Cl IV, Fixed, 95% Cl

SD Total Mean SD Total Weight

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Potential biases in the review process

Acupuncture is not a standardized therapy, and many vari-ables may affect its potential effect on LBP, such as the needling technique, duration, frequency and number of sessions, points treated, manipulation, stimulus intensity, acupuncturists’ experience, patient heterogeneity, and con-founding variables, such as co-interventions or the emotional effect of counseling by the acupuncturists.

SA/PA includes several forms. In this review, one type is a superficial insertion into non-acupuncture points and

nonspecific acupuncture points.10,13,14,24–26_{Another type uses}

a non-penetration method, with sham needles having blunt

and retractable tips.11

For the points treated, some studies used a fixed proto-col for all patients while others used a flexible set of points selected for each patient. Since both the methods are con-sidered valid, this systematic review analyzed them together. Limitations of this meta-analysis include the heterogeneity of the participants, because we included people with both acute and chronic nonspecific LBP, though we had subgroups. If there had been more literature, the evidence of the results would be more convincing with analyzing the types of LBP (acute, sub-acute, and chronic) separately, as they have different clinical approaches and disease trajectories. Additionally, the small num-ber of studies for each SA/PA technique is another limitation. Furthermore, while no regions were excluded, the number of non-English-language journals indexed in electronic databases such as MEDLINE and EMBASE is limited. Should additional relevant trials be identified, this review will be updated.

Conclusion

Implications for practice

Notably, SA/PA was originally developed for use in acu-puncture trials to determine the specific effects of needling. In clinical trials, procedures similar to real acupuncture may

bias the results,27_{and the sham or placebo control should be}

indistinguishable from the active treatment and yet be physi-ologically inert. Without meeting both criteria, it may not be appropriate to regard some procedures as sham or placebo controls within systematic reviews. While this review found evidence that SA/PA is more efficacious than routine care or waiting list in terms of pain relief at the end of the treatments, no evidence existed for improved function.

Additionally, variations of acupuncture must be consid-ered. Based on TCM theory, all acupuncture procedures (e.g., points used, method of stimulation, and number of treatment sessions) must be performed according to individual dif-ferences; thus, acupuncture modalities vary among studies

and are difficult to master and unify.28_{Therefore, studies}

that examine the specific sham or placebo techniques used, including needle placement, needle insertion, acupuncture points or non-acupuncture points or nonspecific acupuncture points, and the acupuncturists’ experience are required, so as to differ distinguish from the real acupuncture. Furthermore, future research should focus on the standardization of out-come measures and the duration and frequency of sessions. Besides, because acupuncture functions as a somato-sensory-guided mind-body therapy, SA/PA could similarly enhance bodily sensations around the treatment site and

Figure 5 Forest plot of comparison between SA/PA and routine care or waiting list for LBP. Outcome: functional disability – RMDQ, PDI, and ODI.

Abbreviations: IV, inverse variance; LBP, low back pain; ODI, Oswestry Disability Index; PA, placebo acupuncture; PDI, Pain Disability Index; RMDQ, Roland–Morris Disability Questionnaire; SA, sham acupuncture; Std, standard.

Study or subgroup 1.2.1 Disability (RMDQ)

Cherkin et al11 _5.4

57.2 77.6

4.9 62.98 45.36

162 63 62

8.9 39 39

6 62.9 62.9

161 30 30

34.7% 32.7% 32.6%

−0.64 [−0.86, −0.41]

0.29 [−0.15, 0.72] 0.74 [0.29, 1.19] 0.11 [−0.78, 1.00]

−0.20 [−0.53, 0.12] −0.69 [−1.15, −0.24] −0.42 [−0.90, 0.05]

−2 −1 0 1 2

287 221

113 110

100.0%

55.4% 44.6% 100.0% 18.8

15.8 13.110.5 70 21.522.3 13.27.8 7439

−0.30 [−0.69, 0.10] 100.0%

44.9 15 50 49.7 16.8 50

−0.30 [−0.69, 0.10] 100.0%

50 50

40

Vas et al14

Brinkhaus et al10

Leibing et al13

Yuan et al28

Heterogeneity: t2_=0.58;_c2_=36.01,_df_{=2 (}_p_<0.00001),_I2_=94%

Test for overall effect: Z=0.25 (p=0.80)

Heterogeneity: t2_=0.08;_c2_=2.94,_df_{=1 (}_p_=0.09),_I2_=66%

Test for subgroup differences: c2_{=1.08, df=2 (}_p_=0.58),_I2_=0%

Subtotal (95% Cl)

Subtotal (95% Cl) 1.2.2 Disability (PDI)

1.2.3 Disability (ODI) Sham

Meanacupuncture Routine care

Sham acupuncture Routine care

Std mean difference Std mean difference

IV, Random, 95% Cl IV, Random, 95% Cl

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Table 2

Summary of findings for the main comparison

Sham or placebo acupuncture versus routine care or no treatment for nonspecific low back pain Outcomes

Illustrative comparative risks

a (95% CI)

Relative effect (95% CI) Number of participants (studies) Quality of the evidence (GRADE)

Comments

Assumed risk

Corresponding risk

Control

Sham or placebo acupuncture versus routine care or no treatment

Pain intensity immediately after the treatment – Pain

(VAS)

The mean pain intensity immediately after the treatment – pain (VAS) ranged across control groups from 39 to 58.6 mm The mean pain intensity immediately after the treatment – pain (VAS) in the intervention groups was 0.36 SD lower (0.54 to 0.18 lower) 624 (6 studies)

⊕⊕⊕⊝ moderate b SMD − 0.36 ( − 0.54 to − 0.18)

Pain intensity immediately after the treatment – Pain

(CPGS)

The mean pain intensity immediately after the treatment – pain (CPGS) across control groups is 57.1 The mean pain intensity immediately after the treatment – pain (CPGS) in the intervention groups was 0.35 SD lower (0.49 to 0.2 lower)

736 (1 study)

⊕⊕⊕⊕ high SMD − 0.35 ( − 0.49 to − 0.2)

Disability immediately after the treatment – Disability (RMDQ) The mean disability immediately after the treatment – disability (RMDQ) ranged across control groups from 8.9 to 39 The mean disability immediately after the treatment

– disability (RMDQ) in the intervention

groups was 0.11 SD higher (0.78 lower to 1 higher) 508 (3 studies)

⊕⊕⊕⊝ moderate SMD 0.11 (−0.78 to 1)

Disability immediately after the treatment – Disability (PDI) The mean disability immediately after the treatment – disability (PDI) ranged across control groups from 21.5 to 22.3 The mean disability immediately after the treatment – disability (PDI) in the intervention groups was 0.42 SD lower (0.9 lower to 0.05 higher) 223 (2 studies)

⊕⊕⊝⊝ low c SMD − 0.42 ( −

0.9 to 0.05)

Disability immediately after the treatment – Disability (ODI) The mean disability immediately after the treatment – disability (ODI) across control groups is 49.7 The mean disability immediately after the treatment – disability (ODI) in the intervention groups was 0.3 SD lower (0.69 lower to 0.1 higher)

100 (1 study)

⊕⊕⊝⊝ low c SMD − 0.3 ( −

0.69 to 0.1)

Notes: aThe basis for the assumed risk (e.g., the median control group risk across studies). The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). GRADE Working Group grades of evidence. High quality ( ⊕⊕⊕⊕ ): further resea rch is very unlikely to change our confidence in the estimate of effect. Moderate quality ( ⊕⊕⊕⊝ ): further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality ( ⊕⊕⊝⊝ ): further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the

estimate. Very low quality (

⊕⊝⊝⊝

): we are very uncertain about the estimate.

bTwo articles lack blinding of participants and personnel. c95% CI includes no effect.

Abbreviations:

CPGS, Chronic Pain Grade Scale; ODI, Oswestry Disability Index; PDI, Pain Disability Index; RMDQ, Roland-Morris Disability Questionnaire; SMD, standard mean difference; VAS, Visual Analog Scale.

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Xiang et al

Figure 6 Subgroup of VAS post-intervention routine care versus waiting list.

Abbreviations: IV, inverse variance; Std, standard; VAS, Visual Analog Scale. Study or subgroup

1.3.1 Pain intensity: acupuncture vs routine care

Brinkhaus et al10 _43.7 32 36 46 33 45 29.8 22 19 27 50.8 70.3 70 40 58 50 62 63

223 157 100.0%

58.6 44 39 58.3 49 49 25.1 17 21 22.5 72.1 72.1 74 39 58 50 30 30 53.8% 38.8% 54.7% 46.2% 3.5% 3.0%

−14.90 [−23.92, −5.88] −12.00 [−20.66, −3.34] −3.00 [−10.29, 4.29]

−12.30 [−22.04, −2.56] 124

120 100.0% −13.70 [−20.32, −7.08] −16.00 [−44.73, 12.73] −4.00 [−35.10, 27.10] −6.98 [−12.37, −1.59]

−100 −50 0 50 100

Leibing et al13 Molsberger et al27

Yuan et al28 Vas et al14 Vas et al14

Test for subgroup differences: c2_=2.38,_df_{=1 (}_p_=0.12),_I2_=58.0%

Test for overall effect: Z=4.06 (p<0.0001) Subtotal (95% Cl)

Subtotal (95% Cl)

1.3.2 Pain intensity: acupuncture vs waiting list Sham

Mean acupuncture Routine care

Favors [experimental] Favors [control] Mean difference Std mean difference IV, Fixed, 95% Cl IV, Fixed, 95% Cl SD Total Mean SD Total Weight

Figure 7 Subgroup of VAS – acute LBP versus chronic LBP.

Abbreviations: IV, inverse variance;LBP, low back pain; VAS, Visual Analog Scale. Study or subgroup

Subtotal (95% CI)

Total (95% CI) 1.4.1 Acute LBP

33 45

43.7 29.8 70 28.6 25.1

17 74 21.5% –14.90 [–23.92, –5.88]–12.00 [–20.66, –3.34]

–3.00 [–10.29, 4.29] –12.30 [–22.04, –2.56] –9.62 [–13.89, –5.36]

–100 –50

Favors [experimental] Favors [control]0 50 100

–9.66 [–13.84, –5.48] 23.3% 32.9% 18.4% 96.1% 100.0% 39 58 50 221 281 21 22.5 44 39 58.3 40 58 50 218 343 22 19 27 32 36 46

50.8 62 49 72.1 30 2.1% –16.00 [–44.73, 12.73]

–4.00 [–35.10, 27.10] –10.47 [–31.58, 10.63] 1.8% 3.9% 30 60 72.1 63 49 125 70.3

1.4.2 Chronic LBP

Vas et al14

Brinkhaus et al10

Leibing et al13

Molsberger et al27

Yuan et al28

Vas et al14

Sham acupuncture Routine care Mean difference

IV, Fixed, 95% CI IV, Fixed, 95% CIMean difference

Mean SD Total Mean SD Total Weight

Heterogeneity: c2_=0.31_;_df_{=1 (}_p_=0.58);_I2_=0%

Test for subgroup differences: c2_=0.01_;_df_{=1 (}_p_=0.94);_I2_=0%

Heterogeneity: t2_=5.07_;_df_{=3 (}_p_=0.17);_I2_=41%

Heterogeneity: t2_=5.38_;_df_{=5 (}_p_=0.37);_I2_=7%

Figure 8 Subgroup of RMDQ – acute LBP versus chronic LBP.

Abbreviations: IV, inverse variance; LBP, low back pain; RMDQ, Roland–Morris Disability Questionnaire.

Study or subgroup Sham acupunctureMean Routine care IV, Random, 95% CIMean difference IV, Random, 95% CIMean difference

57.2 62.98 63 39 62.9 30 29.1% 18.20 [–9.16, 45.56]

38.60 [13.42, 63.78] 29.13 [9.19, 49.07] 30.4% 59.5% 30 60 62.9 39 62 125 45.36 77.6

5.4 4.9 162

162

287 221 100.0%

–100 –50 0 50 100

15.62 [–12.21, 43.45]

8.9 6 161

161 40.5%40.5% –3.50 [–4.70, –2.30]–3.50 [–4.70, –2.30]

Subtotal (95% CI)

Total (95% CI) 1.5.1 Acute LBP

1.5.2 Chronic LBP

Cherkin et al11

Vas et al14

Heterogeneity: t2_=28.13_;_c2_=1.16_df_{=1 (}_p_=0.28);_I2_=14%

Test for subgroup differnces: c2_=10.25_;_df_{=1 (}_p_=0.001);_I2_=90.2%

Heterogeneity: t2_=497.71_;_c2_=13.10_df_{=2 (}_p_=0.001);_I2_=85%

Favors [experimental] Favors [control]

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Dovepress Appropriateness of sham or placebo acupuncture for RCTs induce potential effects related to endogenous pain

modula-tion in the brain.27–29

Thus, we should avoid prematurely concluding that SA/PA is appropriate for acupuncture research. Moreover, guidelines should be developed to assess acupuncture sham– placebo control methods to address the specific effect of acupuncture over placebo.

Implications for research

To provide homogeneous information for future reviews, trial authors are encouraged to use the Consolidated Standards of Reporting Trials (CONSORT) statement as a model for

reporting their trials (www.consort-statement.org) and the

Standards for Reporting Interventions in Clinical Trials of

Acupuncture (STRICTA) criteria30_{to report the interventions.}

From the available trials we included in this meta-analysis, superficial stimulation appears a more promising treatment for LBP than routine care in relieving pain post-intervention. Further studies to assess the superiority of SA/PA are required, as are those with larger sample sizes and those that assess the role of session length by including two (or more) levels of this variable; moreover, the experience of the therapist should also be considered by including practitioners with different levels of experience and training.

Acknowledgment

Prospero registration number: CRD42017070122.

Disclosure

The authors report no conflicts of interest in this work.

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