bmj.com Rapid Responses for Madsen et al., 338 (jan27

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RESEARCH:
Matias Vested Madsen, Peter C Gøtzsche, and Asbjørn Hróbjartsson
Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups
BMJ 2009; 338: a3115 [Abstract] [Full text]

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Rapid Responses published:

Acupuncture; Treatment for Pain: Merian LL Denning (2 February 2009)

Reviewing the reviews on acupuncture for pain: Francesco Crestani, Ali M. Shaladi and Stefano Tartari (4 February 2009)

All noise and no signal: Michael F Vagg (5 February 2009)

A possible double-blind acupuncture placebo needle: Nobuari Takakura, Hiroyoshi Yajima (5 February 2009)

Acupuncture treatment for pain: trial selection and threshold concerns: Lixing Lao, Eric Manheimer, Margaret A. Chesney, Elizabeth Kimbrough Pradhan, Ker Cheng, Brian M. Berman (27 February 2009)

Acupuncture and placebo acupuncture for pain: Asbj�rn Hr�bjartsson, Peter C. G�tzsche (3 March 2009)

Acupuncture - What is the duration of its analgesic efficacy?: Saravanakumar Kanakarajan, Kay Davies (3 March 2009)

Acupuncture for pain: our result is robust to trial selection, and our threshold for minimal clinically effect is low: Asbj�rn Hr�bjartsson, Peter C. G�tzsche (17 March 2009)

Systematic reviews should consider the quality of administration of acupuncture treatment: Zhen Zheng, School of Health Sciences, RMIT University, Bundoora, Victoria 3083, Australia (26 March 2009)

Authors' reply: The quality of the acupuncture interventions was considered in our systematic review: Asbj�rn Hr�bjartsson, Peter C. G�tzsche (5 October 2009)

Re: Systematic reviews should consider the quality of administration of acupuncture treatment: Leigh Jackson (2 November 2009)

What was the research question?: Adrian R White (6 November 2009)

A doubt about the interpretation of the findings: Adrian White (24 November 2009)

Re: A doubt about the interpretation of the findings: Leigh Jackson (29 November 2009)

Acupuncture; Treatment for Pain 2 February 2009

Merian LL Denning,
Vice Chair AACP
Water Lane Clinic, Wilmslow SK95BB
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Re: Acupuncture; Treatment for Pain

Dear Sirs,
The AACP have read with interest your recent publication on the minimal value of acupuncture in the treatment of pain (BMJ 2009;338:a3115)
The Acupuncture Association of Chartered Physiotherapists (AACP) has approximately 5,300 members who use acupuncture as an adjunctive treatment, largely in the management of chronic and acute pain.
We are perplexed that Madsen et al have included in their meta- analysis a study that looked at the value of acupuncture in treating pain from fibromyalgia, a condition where current evidence does not support the use of acupuncture (1).
We also note that the authors have mixed both acute post-operative pain and chronic arthritic pain within your study. In 3 of the thirteen studies that satisfied their inclusion criteria, acupuncture was given once in a post-operative situation while in a further 8 studies it was given 10 or more times for chronic painful conditions. While fulfilling the inclusion criteria of the systematic review, these studies display significant clinical heterogeneity which may well confound the result.
Statistical analysis of non-pharmacological interventions such as physiotherapy and acupuncture, where interventions are non-standardised and issues of blinding complex, are known to be problematic. The use of the STRICTA guidelines as an extension of the CONSORT guidelines will help in future analyses. Future meta-analyses that contain high quality acupuncture trials that display more clinical homogeneity may shed a different light on this 2,000 year old system of health care.
Yours truly,
Merian Denning MSc MCSP
Vice-Chair Acupuncture Association of Chartered Physiotherapists
Reference: Acupuncture for fibromyalgia-a systematic review of randomized clinical trials. Mayhew E, Ernst E. Rheumatology (Oxford) 2007 Vol 46 (5) p801-4
Competing interests: None declared

Reviewing the reviews on acupuncture for pain 4 February 2009

Francesco Crestani,
Pain Unit, San Luca Hospital
45030 Trecenta (Rovigo), Italy,
Ali M. Shaladi and Stefano Tartari
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Re: Reviewing the reviews on acupuncture for pain

Dear Sirs,
Madsen et al. are to be congratulated for their systematic review of trials on acupuncture for the treatment of pain (1). We are not experts in statistics, so we can�t judge their meta-analysis, that we consider mathematically exact. Nevertheless, we have found an oddity in their discussion; in fact in the paragraph �Other studies� they write that their finding of �limited, at best, analgesic effects of acupuncture corresponds with the seven Cochrane reviews on acupuncture for various types of pain, which all concluded that no clear evidence existed of an analgesic effect of acupuncture�. But, reading the conclusions of at least four of these reviews, the results are quite different.
Proctor et al. (2) reviewed the effects on dysmenorrhoea, and they wrote that �there is..insufficient evidence to determine the effectiveness of acupuncture in reducing dysmenorrhoea, however a single small but methodologically sound trial of acupuncture suggest benefit for this modality�.
Trinh et al.(3), discussing acupuncture for neck disorders, concluded that� there is a moderate evidence that acupuncture relieves pain better than some sham treatments..There is a moderate evidence that those who received acupuncture reported less pain at short term follow-up than those on a waiting list. There is also moderate evidence that acupuncture is more effective than inactive treatments for relieving pain post-treatments and this is maintained at short-term follow-up�.
In the authors� conclusions of the meta-analysis on acupuncture for low back pain by Furlan et al.(3) we can read that �the data suggest that acupuncture and dry-needling may be useful adjuncts to other therapies for chronic low-back pain�.
Moreover, Melchart et al. (4) are clearer, writing in their conclusions about acupuncture for headache that �overall, the existing evidence supports the value of acupuncture for the treatment of idiopathic headaches�.
Probably, there are different ways to say the same words.
1) Madsen MV, G�tzsche PC, Hr�bjartsson A. Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ. 2009 Jan 27;338:a3115.
2) Proctor ML, Smith CA, Farquhar CM, Stones RW. Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea. Cochrane Database Syst Rev. 2002;(1):CD002123.
3) Trinh KV, Graham N, Gross AR, Goldsmith CH, Wang E, Cameron ID, Kay T; Cervical Overview Group. Acupuncture for neck disorders. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004870
4) Furlan AD, van Tulder MW, Cherkin DC, Tsukayama H, Lao L, Koes BW, Berman BM. Acupuncture and dry-needling for low back pain. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001351.
5) Melchart D, Linde K, Fischer P, Berman B, White A, Vickers A, Allais G. Acupuncture for idiopathic headache. Cochrane Database Syst Rev. 2001;(1):CD001218.
Competing interest: None declared
Competing interests: None declared

All noise and no signal 5 February 2009

Michael F Vagg,
Pain Specialist
Geelong, Australia
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Re: All noise and no signal

The current systematic review demonstrates eloquently the difficulty in deciding whether a treatment under review is effective if biological plausibility is not taken into account.
So-called Traditional Chinese Medicine (TCM) acupuncture is a prescientific modality, which has a putative mechanism of action which is not supported by physiological and anatomical knowledge. There has not ever been a demonstration of 'chi' which has met scientific standards, nor has any evidence of 'meridians' been adduced to convince scientifically minded practitioners. The details of any meta-analysis or systematic review are unimportant if the concept under review is fundamentally unsound. Recent high-quality acupuncture studies in Germany and the US have succeeded in demonstrating the lack of superiority of sham acupuncture over 'verum' acupuncture. (1,2)Other types of 'acupuncture' including laser acupuncture, auricular acupuncture, electroacupuncture and 'trigger point' acupuncture were never described by the Chinese and need to be evaluated separately from TCM acupuncture.
The at-best-tepidly positive conclusions of large systematic reviews, combined with the implausible mechanism of action given for TCM acupuncture suggest to me as it should to most that these data are all noise and no signal.
1.Acupuncture for Treatment of Persistent Arm Pain Due to Repetitive Use A Randomized Controlled Clinical Trial (Clin J Pain 2008;24:211�218)
2. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. 2006 Jul 4;145(1):12-20
Competing interests: None declared

A possible double-blind acupuncture placebo needle 5 February 2009

Nobuari Takakura,
Professor
2-9-1, Ariake, Koto-ku, Tokyo, 135-0063, Japan,
Hiroyoshi Yajima
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Re: A possible double-blind acupuncture placebo needle

It is definite that blinding of patients and treatment providers (acupuncturist) is crucial to discriminate true treatment effect of needle penetration in future acupuncture trials (1). Madsen et al. suggested that blinding of the healthcare provider can be achieved by having the needling done by acupuncture naive clinicians blinded to the hypothesis of the trials (1) because placebo needles aimed at masking practitioners have been considered unfeasible (2, 3).
However, we reported the design of double-blind (practitioner-patient masking) non-penetrating placebo and matched real needles (fig) with a statistical evaluation of the masking effect of these needles (4, 5). Both needles comprise an opaque guide tube and upper stuffing to give resistance to the needle body during its passage through the guide tube. The needle body of the real needle is longer than the guide tube by an amount equal to the insertion depth, but the needle body of the placebo needle is just long enough to allow its blunt tip to press against the skin when the needle body is advanced as far as possible. The placebo needle contains lower stuffing to give a similar sensation to that of skin puncture and tissue penetration. Both needles have a stopper, which prevents the needle handle from advancing further when the sharp tip of the real needle or the blunt tip of the placebo needle reaches the specified position. The pedestal on each needle is adhesive, allowing it to stick firmly to the skin surface. The appearance and feel of the placebo and real needles are virtually identical.

10 experienced acupuncturists each applied 23 placebo needles and 17 real needles (diameter 0.16 mm) to the LI 4 point, and were asked to guess the nature of each one after removal. They were informed of the possibility of applying an impenetrable needle. Of the 40 needle applications, a mean of 17.0 (SD 4.1) were identified correctly, 6.4 (3.6) were unidentifiable, and 16.6 (3.0) were identified incorrectly.
To test the effectiveness of masking on the patients, we applied the needles to 114 healthy individuals at bilateral TE 5 points. The subjects incorrectly identified 56% of 114 placebo needles and 32% of 114 real needles (5 mm insertion depth).
We believe that these double-blind needles meet the challenge of blinding patients and practitioners in acupuncture trials.
1) Acupuncture treatment for pain: systematic review of randomised clinical trails with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ 2009;338;a3115.
2) Kaptchuk TJ. Placebo needle for acupuncture. Lancet 1998; 352: 992.
3) Kaptchuk TJ, Frank E, Shen J. Methodological issues in trials of acupuncture. JAMA 2001; 285: 1015-6.
4) Takakura N, Yajima H. A double-blind placebo needle for acupuncture research. BMC Complementary and Alternative Medicine 2007;7:31.
5) Takakura N, Yajima H. A placebo acupuncture needle with potential for double blinding- a validation study. Acupunct Med 2008;26(4):224-230.
Competing interests: NT and Hanada Gakuen possess an US patent 6575992B1, a Canadian patent CA 2339223, a Korean patent 0478177, a Taiwan patent 150135, a Chinese patent ZL00800894.9 (Title: Safe needle, placebo needle, and needle set for double blind) and a Japanese patent 4061397 (Title: Placebo needle, and needle set for double-blinding) on the needles described in this manuscript. NT is a salaried employee of Hanada Gakuen and has received research funding from the Hanada Gakuen.

Acupuncture treatment for pain: trial selection and threshold concerns 27 February 2009

Lixing Lao,
Professor
University of Maryland School of Medicine, Center for Integrative Medicine, Baltimore, MD USA 21207,
Eric Manheimer, Margaret A. Chesney, Elizabeth Kimbrough Pradhan, Ker Cheng, Brian M. Berman
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Re: Acupuncture treatment for pain: trial selection and threshold concerns

Madsen and colleagues� recent meta-analysis of acupuncture for pain contains methodological shortcomings and assumptions that render their conclusions problematic.[1]
The authors� stated inclusion criteria required that standard care be applied equally across three study arms of acupuncture, sham acupuncture and no-acupuncture. This requirement appears to have been violated by the inclusion of the trial by Scharf et al. In this study, the no-acupuncture group received up to 10 physician visits that were not offered to the other groups.[2] Its inclusion in the meta-analysis throws into question the exclusion of other studies, such as Berman et al 2004, which tested acupuncture versus sham acupuncture versus education, and found a benefit of acupuncture relative to sham (effect size=0.22 for pain).[3] Furthermore, while 10 of 13 studies in Madsen�s meta-analysis assessed the effect of 6-10 sessions of acupuncture for chronic pain over several weeks, 3 of the 10 studies looked at acupuncture for acute pain over merely 1 day. The substantial heterogeneity observed in the meta-analysis may have resulted from this lack of illness outcome and design specificity.
Madsen and colleagues assert that the effects of true acupuncture relative to sham do not meet thresholds for clinical relevance. However, few if any other commonly-used treatments for knee pain[4] or back pain[5] meet these cut-offs[6] for minimal clinically important differences, including NSAIDS[7] and acetaminophen.[8] This should not be interpreted to mean that we simply have no effective treatment for pain. Rather, it may be that the threshold applied by Madsen et al for clinical relevance is too high for any individual treatment alone, and that a multimodal approach to patient management, with a focus on combining several non- pharmacological therapies[9] is necessary. Many clinicians and patients consider acupuncture as an important treatment option in such an integrative approach[9].
Reference List
1. Madsen MV, Gotzsche PC, Hrobjartsson A. Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ 2009;338:a3115.
2. Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med 2006;145:12-20.
3. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2004;141:901-10.
4. Bjordal JM, Klovning A, Ljunggren AE, Slordal L. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials. Eur J Pain 2007;11:125-38.
5. Deyo RA. Treatments for back pain: can we get past trivial effects? Ann Intern Med 2004;141:957-8.
6. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105- 21.
7. Bjordal JM, Ljunggren AE, Klovning A, Slordal L. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ 2004;329:1317.
8. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006;(1):CD004257.
9. Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 2003;62:1145-55.
Competing interests: None declared

Acupuncture and placebo acupuncture for pain 3 March 2009

Asbj�rn Hr�bjartsson,
Senior Researcher
Nordic Cochrane Centre,
Peter C. G�tzsche
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Re: Acupuncture and placebo acupuncture for pain

In reply to Merian LL Denning, the Vice Chair of the Acupuncture Association of Chartered Physiotherapists, there is no reason to be �perplexed� about our inclusion of a fibromyalgia study, as our aim was to estimate the effect on pain in general. To exclude certain pain conditions because reviews have failed to find an effect, might bias the overall estimate. In this case, however, it makes no difference, as our result is the same after exclusion of this small trial, SMD �0.17 (-0.26 to �0.08) (1).
Denning also criticises the clinical heterogeneity of the included studies. However, we studied a broad research question, as there is no good agreement, or theoretical reason, why acupuncture should be better for some pain conditions than for others. We found that the results of the individual trials of acupuncture vs. placebo did not differ from each other more than is expected by chance after we had excluded a clear outlier from our analyses. When we re-analysed the trials, as suggested by Denning, we found no difference in the effect of acupuncture in trials of short duration, SMD -0.16 (-0.50 to -0.18), and in trials of long duration SMD -0.17 (-0.26 to -0.08).
Francesco Crestani finds that the conclusions of four out of seven Cochrane reviews are �quite different� from how we summarised them. In our discussion we pointed out that none of the 7 Cochrane reviews concluded �clear evidence of an analgesic effect of acupuncture, and most stressed the methodological shortcomings of the included trials.� By clear evidence we understand that a clinically relevant effect has been demonstrated in an analysis involving a low risk of bias and a low risk of chance findings. We revisited the four Cochrane reviews:
Proctor et al. (2) stated in the Author�s conclusion that �There is also insufficient evidence to determine the effectiveness of acupuncture in reducing dysmenorrhoa, however a single small but methodologically sound trial of acupuncture suggest benefit for this modality�. A single small trial does not represent �clear evidence�.
Trinh et al. (3) stated in the Author�s conclusion that there is �moderate evidence� for an effect on neck pain. In the plan language summary they inform us that this is based on small trials, and that they could �only draw limited conclusions�. Moderate evidence, based on small trials involve a considerable risk of bias, and does not represent �clear evidence�.
Furlan et al. (4) wrote in the Author�s conclusion �The data do not allow firm conclusion about the effectiveness of acupuncture for acute low -back pain�, and they stress the low methodological quality of the trials involving chronic low back pain, and call for more trials. This is not �clear evidence�.
Melchart et al. (5) lean towards a positive conclusion: �Overall, the existing evidence supports the value of acupuncture for the treatment of idiopathic headaches�, but their subsequent moderation is important: �However, the quality and amount of evidence are not fully convincing. There is an urgent need for well planned, large scale studies to assess the effectiveness and cost-effectiveness of acupuncture under real-life conditions.� It is hardly �clear evidence� when further studies are urgently needed.
Unfortunately, the review by Melchart et al. is already out of date. Within the same week of the publication of our paper, a new version of was published in The Cochrane Library in which this review was replaced by two reviews by Linde et al. (6,7). In the Author�s conclusion of the first review on migraine prophylaxis Linde et al stated: �There is no evidence for an effect of 'true' acupuncture over sham interventions ��.
In the Author�s conclusion of the second review, on tension type headache, Linde et al. did not differentiate between acupuncture vs. placebo, and acupuncture vs. other control groups. However, in the plain language summary they stated: �Overall, these trials [true acupuncture vs. placebo acupuncture] found slightly better effects in the patients receiving the true acupuncture intervention.�
It is not obvious that �sligthly better� implies a clinically worthwhile effect. Furthermore, the assessment at two months after randomisation (5 trials; 723 patients; one trial providing 70% of the weight) found only marginally statistically significant effects on response rate, and on number of headache days (P values 0.03 and 0.04), and no effect on headache scores (two trials). In our view these small, and marginally statistically effects, in combination with a noteworthy risk of bias, and of chance findings, do not represent �clear evidence�.
We reiterate that none of the 7 reviews summarised by us concluded �clear evidence of an analgesic effect of acupuncture, and most stressed the methodological shortcomings of the included trials.� The general pattern of findings in these reviews, and in the two additional reviews available after the publication of our paper, is fully consistent with our findings that there are small and uncertain effects of acupuncture on pain.
We thank Michael F. Vagg for his comments on the problems of interpreting assessments of effects of interventions that have implausible effect mechanisms. We also thank Nobuari Takakura & Hiroyoshi Yajima for describing a placebo acupuncture needle as a possible tool for assessing effects of acupuncture in a double-blind design.
1. Sprott H, Mennet P, Stratz T et al. Wirksamkeit der Akupunktur bei Patienten mit generalisierter Tendomyopathie (Fibromyalgie). Akt Rheumatol 1993;18:132-5.
2. Proctor ML, Smith CA, Farquhar CM, Stones RW. Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea. Cochrane Database Syst Rev 2002;1:CD002123.
3. Trinh KV, Graham N, Gross AR, Goldsmith CH, Wang E, Cameron ID, Kay T; Cervical Overview Group. Acupuncture for neck disorders. Cochrane Database Syst Rev 2006 3:CD004870.
4. Furlan AD, van Tulder MW, Cherkin DC, Tsukayama H, Lao L, Koes BW, Berman BM. Acupuncture and dry-needling for low back pain. Cochrane Database Syst Rev 2005;1:CD001351.
5. Melchart D, Linde K, Fischer P, Berman B, White A, Vickers A, Allais G. Acupuncture for idiopathic headache. Cochrane Database Syst Rev 2001;1:CD001218.
6. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for tension-type headache. Cochrane Database Syst Rev 2009;1:CD007587.
7. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev 2009;1:CD001218.
Competing interests: None declared

Acupuncture - What is the duration of its analgesic efficacy? 3 March 2009

Saravanakumar Kanakarajan,
Consultant in Anaesthesia and Pain
Aberdeen Royal Infirmary,
Kay Davies
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Re: Acupuncture - What is the duration of its analgesic efficacy?

We read with interest the meta-analysis on acupuncture treatment for pain by Madsen et al (1). They use the sophisticated standardised mean differences of pain scores to compare the effect of acupuncture with placebo and placebo with no acupuncture as well as translate their results to reductions in pain intensity.
The Initiative on Methods, Measurement, and Pain Assessment on Clinical Trials (IMMPACT) attempts to standardise the outcome measures in clinical trials so that clinically meaningful results can be obtained (2). In addition to pain intensity, other recommended domains include physical and emotional functioning, and participant global impression to encompass the different aspects of pain. Based on the research, the provisional benchmark to determine clinically important differences in pain intensity is the percentage reduction in pain intensity. Reductions of 10 -20%, > 30% and > 50% pain intensity reflect minimally important, moderately important clinical change and substantial improvement respectively (3).
Masden et al report a 4 % reduction of pain with acupuncture compared to placebo and 10 % reduction of pain with placebo acupuncture compared to no acupuncture in their meta-analysis. Furthermore, the pain assessment at the first time point after treatment was used in the data extraction. We assume that this is to negate the different duration of treatment, which ranged from 1 day to 12 weeks in the included trials.
Even with the limitations IMMPACT recommendations and the possible data extraction errors (4), the analgesic efficacy of acupuncture seems to be limited for chronic pain. It would be more useful and relevant to know the duration of analgesic efficacy. This would allow both the clinicians and the patients to make more informed recommendations and decisions.
References:
1. Madson MV, Gotzsche PC, Hrobjartsson A. Acupuncture treatment for pain-systemic review of randomised clinical trials with acupuncture, placebo acupuncture and no acupuncture. BMJ 2009; 338: a3115
2. Turk DC, Dworkin RH, Allen RR, Bellamy N et al. Core outcome domains for chronic pain clinical trials. IMMPACT recommendations: Pain 2003; 106: 337-45
3. Dworkin RH, Turk DC, Wyrwich KW et al. Interpreting the clinical evidence of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations: Journal of Pain 2008; 9: 105-121
4. Gotzsche et al. Data extraction errors in meta-analyses that use standardized mean differences JAMA 2007; 298: 430-437.
Competing interests: None declared

Acupuncture for pain: our result is robust to trial selection, and our threshold for minimal clinically effect is low 17 March 2009

Asbj�rn Hr�bjartsson,
Senior Researcher
Nordic Cochrane Centre,
Peter C. G�tzsche
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Re: Acupuncture for pain: our result is robust to trial selection, and our threshold for minimal clinically effect is low

In reply to Lixing Lao et al., our analysis of acupuncture vs. placebo acupuncture (1) is robust to substantial variation in which trials to include, and our threshold for what constitute a minimal clinically relevant difference in effect is, if anything, low.
According to Lao et al. the �inclusion criteria required that standard care be applied equally across three study arms of acupuncture, sham acupuncture and no-acupuncture�. This is not correct. Our inclusion criterion was that equal standard care was intended for all three groups. However, variations in how components of a �standard care package� are utilised easily develop in trials with no treatment groups. Thus, we allowed for, and described in detail, such variations.
Lao et al. are concerned about the inclusion of Scharf et al (2). The standard care package involved 10 �sessions or visits�, up to 6 visits to physiotherapy and variable doses of analgesic drugs (2, Table 1). The �sessions� referred to an acupuncturist in the placebo and acupuncture groups and the �visits� to a general practitioner in the no-acupuncture group. Thus, the standard care package treatment involved the same number of visits/sessions, and the interventions offered were the same (NSAIDs and physiotherapy), but were provided by different types of health providers. We regarded the intended standard care as equal, and we included the trial, but we acknowledge that it may be seen as a borderline decision. Had we excluded the trial it would have made little difference. Our overall estimate of the effect of acupuncture on pain would change only marginally from SMD -0.17 (-0.26 to -0.08) to SMD -0.21 (-0.36 to -0.06).
We excluded Berman et al.�s trial (3) because it compared 23 sessions of acupuncture vs. 23 sessions of placebo acupuncture vs. 6 sessions involving the Arthritis Self-management Program (an �education-attention control� intervention). The trial therefore apparently compared acupuncture, acupuncture-placebo, and attention-placebo, and the groups had very different number of visits/sessions. Had we included the trial (WOMAC pain score at 26 weeks) our pooled effect of acupuncture would change only marginally to SMD -0.18 (-0.26 to �0.10). It would then, however, have been natural also to include two other three-armed acupuncture trials. Diener compared the effect of acupuncture, placebo acupuncture, and standard drug prophylaxis for migraine (4). Haake et al. compared the effect of acupuncture, placebo acupuncture, and guideline based conventional therapy in patients with chronic low back pain (5). Neither trial found a statistically significant effect of acupuncture vs. sham acupuncture on pain scores. The pooled result when adding these two trials to our analyses would have been virtually unchanged: SMD �0.16 (-0.25 to �0.06).
Lao et al. also raise the issue of thresholds for clinical relevance of minor analgesic effects. They state that �However, few if any other commonly-used treatments for knee pain or back pain meet these cut-offs [10 mm on a 100 mm visual analogue scale] for minimal clinically important differences �.� This is incorrect. First, the review on osteoarthritis of the knee quoted by Lao et al. in support of their position (6), reports several interventions with analgesic effects above the 10 mm threshold: oral and topical NSAIDs, intra-articular steroid injection, and opioids (see Figure 1). Other pharmacological interventions, for example, paracetamol, glucosamine sulphate and chondroitin sulphate, did not reach that threshold as they had mean pain reduction of approximately 4 mm. The review defined 12.3 mm as representing �slight improvement� and 19.9 mm �important improvement�, and their conclusion that �clinical effects of pharmacological interventions for OAK [osteoarthrosis of the knee] are small� is fully consistent with this. It is noteworthy that the same lead author reviewed non-pharmacological interventions for the same condition (7), and reported (see Table 4) that manual acupuncture had no statistically significant analgesic effect, 1.3 mm (-2.7 to 4.7).
Furthermore, several systematic reviews have reported analgesic effects of, for example NSAIDs and paracetamol on various pain conditions, which clearly are clinically relevant. The effect of NSAIDs vs. placebo for arthritis related pain was found to be SMD �0.95 in a review of 130 randomised trials (8), and a Cochrane review found that single dose paracetamol caused marked reduction in acute postoperative pain in 50% of patients (9).
Lao et al. generalise to all pain conditions when they state that: �This should not be interpreted to mean that we simply have no effective treatment for pain. Rather, it may be that the threshold applied by Madsen et al. for clinical relevance is too high �.�. This is incorrect. We chose a very low threshold when we applied the 10 mm threshold suggested by IMMPACT for minimal clinically relevant effect (10). It might have been more clinically relevant to choose 20-27 mm, suggested by the IMMPACT to define �some� or �much� improvement. Others have suggested thresholds of 30 mm (11). The implication of Lao et al.�s approach is that a clinically relevant threshold should be set at 3 or 4 mm. Besides the lurking suspicion that thresholds are set according to a desired conclusion, it simply makes no sense with such a minute difference. Furthermore, Lao et al. miss the important point that acupuncture trials are difficult to blind, and that the small effects they find are fully consistent with bias.
Lao et al. suggest that acupuncture should be used as a component in a multidisciplinary package to treat pain. It does not seem rational to include a treatment where randomised trials repeatedly find no or low and uncertain effects, especially when the intervention cannot easily be blinded.
In reply to Saravanakumar Kanakarajan, we agree that the duration of an effect, found to be reliable and large post treatment, is interesting. However, we found a small and uncertain effect of acupuncture on pain, and we therefore think its duration is less interesting.
References
1) Madsen MV, Gotzsche PC, Hrobjartsson A. Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ 2009;338:a3115.
2) Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med 2006;145:12-20.
3) Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2004;141:901-10.
4) Diener HC, Kronfeld K, Boewing G, Lungenhausen M, Maier C, Molsberger A, Tegenthoff M, Trampisch HJ, Zenz M, Meinert R; GERAC Migraine Study Group. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol 2006;5(4):310-6.
5) Haake M, M�ller HH, Schade-Brittinger C, Basler HD, Sch�fer H, Maier C, Endres HG, Trampisch HJ, Molsberger A. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med. 2007;167(17):1892-8.
6) Bjordal JM, Klovning A, Ljunggren AE, Slordal L. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials. Eur J Pain 2007;11:125-38.
7) Bjordal JM, Johnson MI, Lopes-Martins RAB, Bogen B, Chow R, Ljunggren AE. Short-term efficacy of physical interventions in osteoarthritic knee pain: A systematic review and meta-analysis of randomised placebo-controlled trials. BMC Musculosceletal Disorder 2007;8.51
8) G�tzsche PC. Sensitivity of effect variables in rheumatoid arthritis: a meta-analysis of 130 placebo controlled NSAID trials. J Clin Epidemiol 1990;43:1313-8.
9) Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database Syst Rev 2008;(4):CD004602.
10) Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105- 21.
11) ten Klooster PM, Drossaers-Bakker KW, Taal E, van de Laar MA. Patient-perceived satisfactory improvement (PPSI): interpreting meaningful change in pain from the patient's perspective. Pain 2006;121(1-2):151-7.
Competing interests: None declared

Systematic reviews should consider the quality of administration of acupuncture treatment 26 March 2009

Zhen Zheng,
Senior Lecturer, PhD
Traditional & Complementary Medicine Research Group,
School of Health Sciences, RMIT University, Bundoora, Victoria 3083, Australia
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Re: Systematic reviews should consider the quality of administration of acupuncture treatment

Dear Editor,
The systematic review (SR) by Madsen and colleagues aimed to answer a very important question: the difference between real and sham acupuncture for treating painful conditions. The authors have written a review with well-accepted methods and have also considered various threats to the validity of the study. The review failed to discuss two major problems that have impacted on the conclusion: a lack of assessment of the quality of acupuncture treatment and the inclusion of both chronic and acute pain. Consequently, the recommendation of using na�ve acupuncturists in future trials is neither scientific nor ethical.
SRs are more effective in assessing the effectiveness of simple interventions, such as medications, in which the active ingredients and dosage are known, the delivery modes are standardised and the therapists can be effectively blind to group allocation. Complex interventions, such as acupuncture, pose challenges to SRs. Herbert and B� (1) argued that how well complex interventions were administered influenced the results and conclusions of SRs. They demonstrated that when trials of well and poorly administered pelvic floor exercise programs for urinary incontinence were included in one review, the pooled result showed that exercise was not effective for the condition. When they removed one trial with a poorly administered exercise program from the analysis, the pooled result became statistically and clinically significant, indicating exercise was effective.
The same argument applies to SRs of acupuncture. It is commonly agreed that an effective acupuncture treatment should induce De Qi sensation, be delivered by experienced acupuncturists and have a certain number of sessions of treatment (2, 3). Madsen and colleagues have selected studies accordingly. Their approach is commendable. Such strategies are, however, insufficient. Unless the administration of acupuncture treatment is of high quality and comparable among selected studies, the conclusion of the SR is invalid.
Let us compare two studies to see the problems I have raised. In recent years, two large acupuncture clinical trials for tension type of headache were conducted in Germany (4, 5). The Melchart study was included in the Madsen review. The designs of the two trials were similar: both were multi-centre trials, compared real with sham acupuncture, selected similar acupuncture points, and the treatment was delivered by physicians who had similar qualifications. The results are, however, different. For headache days, the weighted mean difference in Melchart�s study was -0.90 (95% CI -3.57 to 1.77), and in Endres�s was -2.30 (95% CI -3.75 to -0.80). The Endres study demonstrated that real acupuncture was significantly better than sham acupuncture. The only possible explanation of the disparity in the results is the administration of acupuncture and the adherence to protocol. In the Melchart study, 42 physicians treated 270 patients with the length of physicians� practice varying from 1 to 41 years. Furthermore, one of the eight centres that delivered 214 out of 1507 sessions of treatment did not use two of the three mandatory points for 80% of their patients. Chinese medicine diagnosis was not mandatory and �De Qi was achieved if possible� (6). In contrast, in the Endres study, more than 112 physicians treated 413 subjects. Individual diagnosis was applied. More importantly, mandatory points had to be needled in every patient and in every session, �De Qi � had to be elicited at all points�, and needles were manipulated 2-3 times during the treatment to achieve consistent De Qi. Independent clinical monitors visited the trial centres repeatedly to ensure the quality of the intervention (7).
It is not surprising that the recent CONSORT statement on trials assessing non-pharmacological treatments (8) expanded the �Invention� section from one item in the previous statement (9) to three items. The statement also emphasises the inclusion of experienced therapists. For instance, trial surgeons must be experienced in and comfortable with the studied surgical procedure. With multi-centre trials, the distribution of experts in different centres and in each group, and the expertise of each centre are recommended to be reported in the trial because these factors impact on the quality of administration of interventions and affect the review outcomes (10).
The authors of the Madsen review should have discussed the above- mentioned confounding factors before concluding that acupuncture has only a small analgesic effect that is of little clinical relevance. The suggestion of using �na�ve clinicians� so as to ensure the blinding of therapists is not scientifically sound and clearly against the CONSORT statement as outlined above. Such a suggestion will only introduce more variances. The suggestion is also unethical, being against the International Conference on Harmonization Guideline for Good Clinical Practice (ICH-GCP) E6 (1996). Item 4 states that in order to protect trial subjects, the investigators should meet �all the qualifications specified by the applicable regulatory requirement(s)�and their qualifications should be up-to-date. I would be very concerned if I were a subject in an acupuncture trial where the therapist is a �na�ve� acupuncturist. I would also be concerned if any Human Research Ethics Board or Committee approves such practice in acupuncture trials.
The second weakness of including both acute and chronic pain has been pointed out by other readers, and I shall restrict my comments to those aspects that have not been discussed. Fibromyalgia (FM) is quite different from commonly seen musculoskeletal conditions, such as lower back pain or keen pain. One study showed that both real and sham acupuncture increased the blood flow in the muscle of FM patients; whereas in the healthy humans, only real acupuncture had this effect (11). The results indicated that both types of acupuncture could be similarly effective in FM patients, possibly due to physiological, rather than psychological factors. Experienced acupuncturists would know that only shallow needling, as that used in sham acupuncture, is to be used in FM at the early stage because patients are often extremely sensitive to needling.
The Madsen review provokes more questions than it provides answers. Future SRs need to take the quality of treatment administration and adherence to protocol into account. These factors of acupuncture treatment need to be further studied in relation to their impact on the outcomes. In addition, before we understand the underlying mechanisms of FM, SRs of pain should not confuse wide-spread musculoskeletal pain with other types of pains.
References
1. Herbert RD, B� K. Analysis of quality of interventions in systematic reviews. BMJ 2005;331:507-9.
2. MacPherson H, White A, Cummings M, Jobst K, Rose K, Niemtzow R. Standards for reporting interventions in controlled trials of acupuncture: the STRICTA recommendations. Complement Ther Med 2001;9(4):246-9.
3. Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB. Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain 2000;86:217-25.
4. Melchart D, Streng A, Hoppe A, Brinkhaus B, Witt C, Wagenpfeil S, et al. Acupuncture in patients with tension-type headache: randomised controlled trial. BMJ 2005;331(7513):376-82.
5. Endres HG, al e. Acupuncture for tension-type headache: a multicentre, sham-controlled, patient-and observer-blinded, randomised trial. . J Headache Pain, 2007;8(5):306-14.
6. Melchart D, Streng A, Hoppe A, Brinkhaus B, Becker-Witt C, Hammes M, et al. The acupuncture randomised trial (ART) for tension-type headache --details of the treatment. Acupunct Med. 2005;23(4):157-65.
7. Molsberger AF, Boewing G, Diener HC, Endres HG, Kraehmer N, Kronfeld K, et al. Designing an acupuncture study: the nationwide, randomized, controlled, German acupuncture trials on migraine and tension- type headache. J Altern Complement Med. 2006;12(3):237-45.
8. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, Group tC. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med 2008;148:295-309.
9. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med 2001;134:657-62.
10. Halm EA, Lee C, Chassin MR. Is volume related to outcome in health care? A systematic review and methodologic critique of the literature. Ann Intern Med 2002;137:511-20.
11. Sandberg M, Lindberg LG, Gerdle B. Peripheral effects of needle stimulation (acupuncture) on skin and muscle blood flow in fibromyalgia. Eur J Pain 2004;8(2):163-71.
Competing interests: Dr Zheng is a researcher, educator and practitioner of acupuncture. She specialises in pain research. Dr Zheng is the Editor in Chief of Australian Journal of Acupuncture and Chinese Medicine, and is a board member of Australian Acupuncture and Chinese Medicine Association.

Authors' reply: The quality of the acupuncture interventions was considered in our systematic review 5 October 2009

Asbj�rn Hr�bjartsson,
Senior Researcher
The Nordic Cochrane Centre,
Peter C. G�tzsche
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Re: Authors' reply: The quality of the acupuncture interventions was considered in our systematic review

In reply to Dr. Zheng (1), it is not correct that our way of dealing with the quality of the acupuncture treatment goes �clearly against the CONSORT statement� for non-pharmacological trials (2). We both contributed to this CONSORT document, and we therefore obviously agree with Dr. Zheng that it is important to report in detail the interventions of non- pharmacological trials. In coherence with this, we carefully described the type of acupuncture intervention in each included trial in Table 2. We also studied whether the effect of acupuncture was different in the subgroup of trials with experienced acupuncturists, which could select their acupuncture points at their will, but found no such difference.
Dr. Zheng believes our approach is insufficient and states that �Unless the administration of acupuncture treatment is of high quality and comparable among selected studies, the conclusion of the SR [systematic review] is invalid.� This is not a valid statement for systematic reviews in general, or in this particular case where the intervention was acupunture, and where we also looked at the subgroup of trials with experienced acupuncturists. Furthermore, we think Dr. Zheng has misunderstood the nature of our conclusion. Our conclusion was not that acupuncture had no effect, but that the studies we reviewed found no or small effects in general.
We recommended that future acupuncture trials should �try to reduce bias by ensuring blinding when possible.� Subsequently, we gave an example of how this could be obtained, by using acupuncture na�ve clinicians. We could have made it clearer that this suggestion implies an explanatory trial design with a very strict acupuncture treatment plan with no room for individualisation of acupuncture points or other treatment variations. Such a design is neither unethical nor unscientific, as suggested by Dr. Zheng, just different from a clinically orientated pragmatic trial design. Blinding of the acupuncturist in a more pragmatic trial design with experienced acupuncturists who are free to individualise their treatments may possibly be achieved by using the needle developed by Takakura (3).
We have addressed the question of pooling trials with acute and chronic pain in a previous reply, but reiterate that there was no statistically significant difference between the effects of acupuncture on the two types of pain.
Dr. Zheng refers to a trial that reported unusually large effects of acupuncture on headache (4). The trial was not conducted as a three-armed trial, and was therefore not eligible for our review. We are concerned about the substantial risk of cherry-picking an outlier when discussing the effect of an intervention.
Asbj�rn Hr�bjartsson Peter C G�tzsche
1) Zheng Z. Systematic reviews should consider the quality of administration of acupuncture treatment. BMJ Rapid responses (26 March); 2009. www.bmj.com/cgi/eletters/338/jan27_2/a3115#211132.
2) Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, CONSORT Group. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med 2008;148:295-309.
3) Takakura N, Yajima H. A placebo acupuncture needle with potential for double blinding- a validation study. Acupunct Med 2008;26:224-230.
4) Endres HG, B�wing G, Diener HC, Lange S, Maier C, Molsberger A, Zenz M, Vickers AJ, Tegenthoff M. Acupuncture for tension-type headache: a multicentre, sham-controlled, patient-and observer-blinded, randomised trial. J Headache Pain, 2007;8:306-14.
Competing interests: None declared

Re: Systematic reviews should consider the quality of administration of acupuncture treatment 2 November 2009

Leigh Jackson,
Community worker
Wandsworth, SW12 9PZ
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Re: Re: Systematic reviews should consider the quality of administration of acupuncture treatment

The Endres study (1) compared quality controlled traditional Chinese acupuncture for tension headache, with sham acupuncture.The sham treatment involved superficial needling, without needle stimulation at non- acupuncture points. Elicitation of "De Qi" was avoided for the control treatment, as was the placement of needles on the head. The last two restrictions could have had the consequence of reducing the strength of any placebo effect compared with verum acupuncture.
"Neverthless", the authors commented, "the response in the sham group appears unusually large for a �placebo� arm in a randomised trial." (For primary endpoints the response was 33% verum vs 27% sham.)
The conclusion of Endres coheres with Madsen: "the degree to which treatment benefits depend on psychological compared to physiological effects and the degree to which any physiological effects depend on needle placement and insertion depth are unclear."
The quality of traditional Chinese acupuncture treatment in the Endres study - only one of the many forms of acupuncture - does not have implications for the validity of the study by Madsen and colleagues.
1. Endres HG, al e. Acupuncture for tension-type headache: a multicentre, sham-controlled, patient-and observer-blinded, randomised trial. . J Headache Pain, 2007;8(5):306-14.
Competing interests: None declared

What was the research question? 6 November 2009

Adrian R White,
Seniorforsker
The National Research Center in Complementary and Alternative Medicine, University of Troms�, N-9037
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Re: What was the research question?

The authors of this review stated that their aim was �to study the analgesic effect of acupuncture and placebo acupuncture�. There could be at least three different ways to operationalise these aims as research questions. Each requires a different study method and analysis. The authors seem to intend to address parts of each question, and so their methodology may not be entirely appropriate.
1. Is acupuncture a clinically relevant treatment for chronic pain? The way to address this question would be to compare the normal practice of acupuncture with usual care, and with other existing treatments. There is no reason to limit the evidence to three arm studies. And there is no reason to simply compare acupuncture and �placebo� acupuncture, as done here: the clinical impact of every physical treatment incorporates both psychological and physical components, which are not delivered separately. We would get more of an impression of the clinical value of acupuncture if we combined the results of the two analyses (acupuncture vs �placebo�, and �placebo� vs usual care). This gives an overall acupuncture treatment effect of about 14mm, which is hardly large but may meet the authors� definition of �clinically relevant�. Thus, the analysis used in the review seems inappropriate for the conclusion they made, that the analgesic effect of acupuncture seems to lack clinical relevance.
2. Is acupuncture just a placebo? The authors seem interested in two parts to this question: whether needles have neurophysiological effects of their own, separate from their psychological effects; and, what is the size of the psychological (placebo) effect of acupuncture. At first sight, it seems appropriate to compare acupuncture with �placebo� acupuncture. However, in the Introduction the authors summarise the neurophysiology of acupuncture with the statement: �Studies indicate that penetration of a needle through the skin, whether at an acupuncture point or not, has physiological effects�. Unfortunately, this sentence renders most of their data irrelevant: if needles inserted at non-acupuncture points have physiological effects, they are not a �placebo� and studies using them cannot be included. Only two trials included in the review used needles that did not penetrate the skin and might be placebo, though there is some doubt about whether even non-penetrating needles are completely inert.[1 2] This placebo control problem in acupuncture research is well recognised and unfortunately not overcome by the methodology used here. So the study had little chance of providing any conclusions about whether acupuncture is just a �placebo�, or about the size of the effect of �placebo� acupuncture.
3. Is acupuncture a panacea for pain? This seems to be the authors� main question, expressed mostly clearly in the Discussion and in the Rapid Responses as �an effect on pain in general�. This phrase was used to justify the inclusion of studies in different pain conditions, such as osteoarthritis, fibromyalgia, procedural pain, migraine and postoperative pain. However, it is well accepted that there are several different types of pain (e.g. some do not respond well to morphine) which need different treatments.[3] So the hypothesis that acupuncture is a panacea for pain is surprising and not really scientifically based. It requires some reference to justify it, but none is given. No acupuncturist of my acquaintance has ever made this claim, nor can I readily find it in a peer reviewed publication. I suppose there may be some people on the fringes of acupuncture with little clinical experience of real patients who might say such a thing out of ignorance or innocence, but they make a rather soft target. The methodology may be appropriate for addressing this question, but the question seems rather pointless. It may be that the authors are concerned about the exaggerated claims that are sometimes made for acupuncture, which could be a significant problem. If so it would seem that the appropriate methodology would not be meta-analysis, but regulation.
I have only outlined three possible research questions, and there may be others that the authors were really addressing. It would be interesting to hear from them, so that we can judge how this work stands in relation to the cautious effort to build up the primary evidence on whether or not acupuncture can contribute to the wellbeing of patients, as exemplified by the journal Acupuncture in Medicine. [4]
References
1. Lund I, Lundeberg T. Are minimal, superficial or sham acupuncture procedures acceptable as inert placebo controls? Acupunct. Med 2006;24(1):13-15.
2. Lund I, Naslund J, Lundeberg T. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective. Chinese Medicine 2009;4(1):1.
3. Woolf CJ, Decosterd I. Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients. Pain 1999;Suppl 6:S141-7.
4. White A, Med EBoA. Western medical acupuncture: a definition. Acupunct Med 2009;27(1):33-5.
Competing interests: The author has received fees for lecturing on acupuncture and is paid as the editor in chief of Acupuncture in Medicine, which aims to provide an unbiased approach to the evidence on acupuncture�s place in health care using a western scientific approach

A doubt about the interpretation of the findings 24 November 2009

Adrian White,
Senior researcher
NAFKAM The National Research Center in Complementary and Alternative Medicine, Univ of Troms�
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Re: A doubt about the interpretation of the findings

Madsen et al found a significant difference between acupuncture and �placebo� acupuncture. This difference was robust, remaining significant in subgroup analyses of different outcome measures and of high quality studies.
In interpreting this finding, the authors state that this effect �cannot be clearly distinguished from bias�. They state that these biases arise because patients may distinguish real acupuncture from �placebo� acupuncture, and because patients interact with practitioners who cannot be blinded so may subconsciously influence the outcome.
These inherent biases presumably apply to all placebo controlled studies of acupuncture, in any condition that can respond to non-specific influences. It is noteworthy, therefore, that a meta-analysis of RCTs of acupuncture for migraine shows no difference between acupuncture and �placebo� acupuncture. This was a robust finding which applied both immediately after treatment (seven studies, 1091 patients) and after 3-4 months (11 studies, 1225 patients).[1] It is known that migraine does respond to non-specific influences.[2] The fact that these biases, which these authors claim are inherent in acupuncture, have no effect in studies of acupuncture for migraine argues against their existence in studies of acupuncture for other painful conditions.
Thus it appears that the inherent bias that Madsen et al refer to in these studies is either very small or non-existent. And so it seems more logical to interpret their findings as showing that acupuncture has a significant analgesic effect that is small but robust.
Competing interest The author is paid as the editor in chief of Acupuncture in Medicine.
References 1. Linde K, Allais G, Brinkhaus B, et al. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev 2009(1):CD001218. 2. Macedo A, Banos JE, Farre M. Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain 2008;12(1):68-75.
Competing interests: The author is paid as the editor in chief of Acupuncture in Medicine

Re: A doubt about the interpretation of the findings 29 November 2009

Leigh Jackson,
Community workerw
Wandsworth, SW12 9PZ
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Re: Re: A doubt about the interpretation of the findings

There is an inherent risk of bias in all non-blinded clinical trials. Linde et al. explicitly recognise that bias might have affected their results (1). Madsen et al. and Linde et al. each found a small analgesic benefit for acupuncture compared with no acupuncture.
Madsen et al. conclude that the small benefit of acupuncture does not have clinical relevance and could be due to bias. Linde et al. conclude simply that acupuncture is slightly more effective and has fewer side effects than prophylactic drug treatment. Linde et al. appear to take a more sanguine view of the possible effects of bias than the more cautious view expressed by Madsen et al.
References 1. Linde K, Allais G, Brinkhaus B, et al. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev 2009(1):CD001218.
Competing interests: None declared