WHITE Adrian

WHITE, Adrian

Meiji University of Integrative Medicine Academic Repository

明治国際医療大学誌第 1回国際シンポジウム　第一部－統合医療の確立に向けて－明治国際医療大学誌　創刊号：23–28，2009© 明治国際医療大学Recent Progress in Clinical Research of AcupunctureAdrian WHITEClinical Research Fellow, General practice and Primary Care, Institute of Health and Social Care, Peninsula Medical School, Universities of Exeter and PlymouthIntroductionI.  This report mainly summarise the results of recent clinical trials and systematic reviews of acupuncture on musculoskeletal disorders. Several issues regarding sham intervention and placebo eff ects in acupuncture trials are discussed because they aff ect the way clinical research should be interpreted. Results of cost-eff ectiveness analysis of acupuncture trials are also briefl y introduced. Research on safety of acupuncture could not be referred in detail but its safety is confi rmed in numerous clinical trials. Evidence of effectiveness of acupunctureII.  1. Randomized controlled trial (RCT)A series of carefully designed, large scale, three-arm RCTs compared acupuncture with sham (off  point, shallow) needling and with usual care were conducted in German with fi nancial support by the German insurance companies. The target diseases were musculoskeletal disorders such as knee osteo-arthritis, low back pain, migraine and tension-type headache. Figure 1 shows two typical examples of three arm RCTs of knee pain. One is real acupuncture, sham acupuncture and waiting list, and the other is real acupuncture, sham acupuncture and drug therapy. The pain was measure using WOMAC score. Acupuncture induced long-lasting pain suppression. Both RCTs indicate signifi cantly stronger eff ects of acupuncture than waiting list or drug therapy groups.In general, recent RCTs demonstrated that acupuncture is signifi cantly bett er than usual care for patients. The size of the eff ect was clinically useful. But in the comparisons with sham acupuncture, acupuncture repeatedly showed a non-signifi cant trend towards superiority. It was only signifi cantly superior in one study of acupuncture for osteo-arthritis of the knee. (see Figure 1, Witt  2005). Safety of acupuncture intervention by trained practionaers has been well established in several diff erent countries. Witt 2005  n=300010203040506070AcupunctureS ham acupWaiting list*S c harf 2006  n=100705101520253035404550AcupunctureS ham acupDrug therapy**Fig. 1. Two RCTs of acupuncture on knee painThe Bulletin of Meiji University of Integrative Medicine24 明治国際医療大学誌　創刊号2. Systematic review and meta-analysis of clinical trialsSystematic reviews of RCTs represent the highest level of evidence, and the increasing number of high quality trials has allowed recent reviews to provide a more reliable summary of the evidence on acupuncture. Figure 2 and 3 demonstrate the results of meta-analysis using pooled data of several RCTs of acupuncture for knee pain In comparison of real acupuncture with usual care, a highly signifi cant diff erence, favour to acupuncture, was obtained (Fig. 2, p<0.00001). Slight but still signifi cant diff erence was observed in comparison of real acupuncture with sham acupuncture. (Fig. 3, p<0.01).In two cases, earlier reviews which were unable to reach conclusions have now been updated, with positive results. For low back pain (Manheimer et al. 651–63) and for osteoarthritis of the knee, (White et al. 384–90) acupuncture is superior both to sham acupuncture and to usual care. Although the size of the eff ect of acupuncture when compared with sham is not large, the size of acupuncture’s eff ect on knee pain is large enough to be similar or even superior to the eff ect of non-steroidal anti-infl ammatory drugs (NSAIDs). Figure 4 illustrates the comparison of eff ect sized between them.It is interesting to note that two recent, high quality studies showed no eff ect of acupuncture for knee pain compared with sham acupuncture; in Real acupuncture vs usual carepain, short term (N=927)Fig. 2. Meta-analysis of acupuncture on knee OA. White et al. Rheumatology 2007; 46(3): 384-90.Real acupuncture vs sham acupuncturepain, short term (n=1334)*Fig. 3. Meta-analysis of acupuncture on knee OA. Modifi ed from White et al. Rheumatology 2007.明治国際医療大学誌25Recent progress in clinical research of acupunctureboth studies, acupuncture was given in addition to exercise therapy. It seems probable that exercise allowed patients to achieve the maximum improve-ment possible and acupuncture could have no addi-tional benefi t (called a ‘ceiling eff ect’). In comparison with sham acupuncture, acupuncture has a signifi cant eff ect on post-operative pain, a signifi cant but somewhat limited eff ect on tension headache, and (at least for electroacupuncture) an eff ect on fi bromyalgia. The current evidence is moderately in favour of an eff ect on neck pain, and there is insuffi  cient evidence on elbow pain. In contrast, there is no eff ect on migraine compared to sham. Systematic reviews have for some years consistently demonstrated that acupuncture is eff ective for nausea and vomiting. More recently, acupuncture was shown to be eff ective as an adjunct to infertility treatment and in generalised anxiety disorder, but in both cases the amount of evidence is somewhat limited. Systematic reviews have found insuffi  cient good quality evidence for estimating its eff ect on asthma, bowel diseases, hay fever or insomnia. Current evidence suggests acupuncture is not eff ective in smoking cessation or for recovery from stroke.Components of acupuncture treatmentIII.  An important step forward in understanding acupuncture was the recent study confi rming what had long been suspected, but never proved – that a large part of the eff ect of acupuncture is due to the patient’s expectation, loosely called the ‘placebo’ eff ect. In patients with irritable bowel syndrome, the eff ect of needling is much greater when it is accompanied by the full, elaborate procedures involved in the acupuncture consultation. Expectation plays a part in all medical interventions, but it now seems very likely that the expectation of acupuncture is much greater than that of conventional medical treatment, at least when the patient considers acupuncture to be ‘unconventional’.The question arises: is it very important that a large part of acupuncture’s eff ect is due to expectation? The answer will depend on your viewpoint, and is the distinction between clinical relevant eff ect and biological eff ect. Patients and their health care staff  will be more concerned with whether acupuncture will improve the patient’s symptoms than what is its mode of action. They will accept acupuncture if trials show that it off ers additional benefi ts compared with usual treatment. But scientists, and health care regulators, are more likely to reject acupuncture, on principle, if it cannot be shown to be even slightly superior to placebo, in other words to have a ‘specifi c’ eff ect. The placebo question has dominated the approach to acupuncture research for the last decade, which may not have been in the best interests of patients. In addressing the placebo question, two problems arise: 1) it seems that this ‘specifi c’ eff ect of acupuncture is small in relation to its expectation eff ects, and therefore clinical trials need to be very large to demonstrate it. 2) these studies require an inactive ‘placebo’ control for acupuncture.‘Placebo’ (sham) controlsIV.  Finding an inactive ‘placebo’ control for acupuncture LargeMediumSmallFig. 4. Comparison of eff ect size of acupuncture and NSAIDs on knee pain. White and Kawakita Acupunct Med 2006; 24(supp): 71-6.The Bulletin of Meiji University of Integrative Medicine26 明治国際医療大学誌　創刊号is diffi  cult. In the most common version, used in many trials, the control group have received acupuncture needles, but inserted in the wrong site and only superfi cially, and not stimulated. The patients oft en believe that they have been given real acupuncture, but this treatment may not be inactive – superfi cial needling is used as a form of treatment in some sett ings. An additional, more theoretical, limitation of the ‘placebo’ control is that it only applies in traditional approach to acupuncture, in which it is believed that the correct point has to be treated. Increasing numbers of acupuncturists are coming to use a medical approach to acupuncture, in which reduces the importance of specifi c acupuncture points, and emphasises the need to stimulate the nervous system in an appropriate way. Needles do not have to be inserted in specifi c points, and needles inserted into the same spinal segment as the pain, as done in these control groups, may be an active treatment. The search for a suitable placebo for acupuncture appeared to be over when a blunt, telescopic needle was developed. However, it now seems that this device, even though it amounts to no more than light touch, has signifi cant eff ects on the pain matrix of the brain, and is far from inactive. (Pariente et al. 1161–67) Although these eff ects are signifi cant, they are nevertheless diff erent from the eff ects of needling. It has been suggested that the blunt needle stimulates a subgroup of the C fi bres in the skin, the so-called C-tactile fi bres. Since these controls are active, they should be called ‘sham’ rather than ‘placebo’. Evidence of cost-effectivenessV.  Clinical trials with full economic analysis have now been conducted on acupuncture for migraine, back pain, and osteoarthritis of knee and hip. The results are summarized in Table 1. In all cases, the results indicated that the additional cost of acupuncture was less than £20,000 per Quality Adjusted Life Year (QALY). This is the limit usually applied for accepting treatments for the health care of an industrialised nation, and may mean that acupuncture should be adopted more widely. Making decisions on health care on the basis of best value for money.ConclusionVI.  1. Acupuncture is more eff ective than placebo (sham) for some conditions (knee OA, low back pain and neck pain).2. Acupuncture is clearly more eff ective than usu-al care for several conditions (migraine, tension headache).3. Cost- eff ectiveness of acupuncture is relatively high comparing with usual drug therapies.Implications for future research1. Three-arm studies must be approached with great caution. 2. For eff ectiveness question, acupuncture should be compared with standard care using multi-centre, pragmatic trial design.3. For specifi c eff ect question, acupuncture should be compared with non-penetrating placebo, in a single centre, fastidious experimental design.Condition Author N Cost/QALY yenMigraine Vincent, Wonderling 283 £ 9,951 ¥ 2,044,703Headache Witt 3182 £ 9,326 ¥ 1,916,279Low back pain Thomas, Ratcliffe 182 £ 4,241 ¥ 871,428Low back pain Witt 3093 £ 8,420 ¥ 1,730,117Neck pain Willich 3451 £ 9,975 ¥ 2,049,634Knee pain Reinhold 489 £ 14,276 ¥ 2,933,391Maximum acceptable in UK is £20,000 per QALY (about ¥4,100,000) QALY: Quality Adjusted Living YearsTable 1. Cost-eff ectiveness of acupuncture明治国際医療大学誌27Recent progress in clinical research of acupunctureReferences[RCT, knee OA]Witt  C, Brinkhaus B, Jena S, Linde K, Streng A, Wagenpfeil S et al. Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet 2005; 366(9480): 136-43.Berman BM, Singh BB, Lao L, Langenberg P, Li H, Hadhazy V et al. A randomized trial of acu-puncture as an adjunctive therapy in osteo-arthritis of the knee. Rheumatology (Oxford) 1999; 38(4): 346-54.Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Eff ectiveness of acupunc-ture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2004; 141(12): 901-10.Scharf HP, Mansmann U, Streitberger K, Witt e S, Kramer J, Maier C et al. Acupuncture and knee osteoarthritis - a three-armed randomized trial. Ann Intern Med 2006; 145(1): 12-20.Takeda W, Wessel J. Acupuncture for the treatment of pain of osteoarthritic knees. Arthritis Care Res 1994; 7(3): 118-22.Tukmachi E, Jubb R, Dempsey E, Jones P. The eff ect of acupuncture on the symptoms of knee os-teoarthritis--an open randomised controlled study. Acupunct Med 2004; 22(1): 14-22.Vas J, Mendez C, Perea-Milla E., Vega E, Panadero MD, Leon JM et al. Acupuncture as a comple-mentary therapy to the pharmacological treat-ment of osteoarthritis of the knee: randomised controlled trial. BMJ 2004; 329(7476): 1216-9.[RCT, low back pain]Brinkhaus B, Witt  CM, Jena S, Linde K, Streng A, Wagenpfeil S et al. Acupuncture in patients with chronic low back pain: a randomized con-trolled trial. Arch Intern Med 2006; 166(4): 450-7.Haake M, Muller HH, Schade-Britt inger C, Basler HD, Schafer H, Maier C et al. German Acu-puncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, paral-lel-group trial with 3 groups. Arch Intern Med 2007; 167(17): 1892-8.[Systematic Review, knee pain]White A, Foster NE, Cummings M, Barlas P. Acu-puncture treatment for chronic knee pain: a systematic review. Rheumatology (Oxford) 2007; 46(3): 384-90.White A, Foster N, Cummings M, Barlas P. The ef-fectiveness of acupuncture for osteoarthritis of the knee - a systematic review. Acupunct Med 2006; 24 Suppl: S40-S48.White A, Kawakita K. The evidence on acupuncture for knee osteoarthritis - editorial summary on the implications for health policy. Acupunct Med 2006; 24 Suppl: S71-S76.[Systematic Review, low back pain]Manheimer E, White A, Berman B, Forys K, Ernst E. Meta-analysis: acupuncture for low back pain. Ann Intern Med 2005; 142(8): 651-63.[Expectation; Placebo effects]Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE et al. Components of placebo eff ect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 2008; 336(7651): 999-1003.Pariente J, White P, Frackowiak RS, Lewith G. Ex-pectancy and belief modulate the neuronal sub-strates of pain treated by acupuncture. Neuro-image 2005; 25(4): 1161-7.[Sham acupuncture]Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. Lancet 1998; 352: 364-5.Park J, White A, Stevinson C, Ernst E, James M. Vali-dating a new non-penetrating sham acupunc-ture device: two randomised controlled trials. Acupunct Med 2002; 20(4): 168-74.Takakura N, Yajima H. A double-blind placebo nee-dle for acupuncture research. BMC Complement Altern Med 2007; 7: 31.[Cost-effectiveness of acupuncture]Wonderling D, Vickers AJ, Grieve R, McCarney R. Cost eff ectiveness analysis of a randomised tri-al of acupuncture for chronic headache in pri-mary care. BMJ 2004; 328(7442): 747-9.Witt  CM, Reinhold T, Jena S, Brinkhaus B, Willich SN. Cost-eff ectiveness of acupuncture treat-ment in patients with headache. Cephalalgia The Bulletin of Meiji University of Integrative Medicine28 明治国際医療大学誌　創刊号2008; 28(4): 334-45.Ratcliff e J, Thomas KJ, MacPherson H, Brazier J. A randomised controlled trial of acupuncture care for persistent low back pain: cost eff ective-ness analysis. BMJ 2006; 333(7569): 626-628A.Witt  CM, Jena S, Selim D, Brinkhaus B, Reinhold T, Wruck K et al. Pragmatic randomized trial eval-uating the clinical and economic eff ectiveness of acupuncture for chronic low back pain. Am J Epidemiol 2006; 164(5): 487-96.Willich SN, Reinhold T, Selim D, Jena S, Brinkhaus B, Witt  CM. Cost-eff ectiveness of acupuncture treatment in patients with chronic neck pain. Pain 2006; 125(1-2): 107-13.Reinhold T, Witt  CM, Jena S, Brinkhaus B, Willich SN. Quality of life and cost-eff ectiveness of acu-puncture treatment in patients with osteoar-thritis pain. Eur J Health Econ 2007; 9(3): 209-19.Witt  CM, Brinkhaus B, Reinhold T, Willich SN. Effi  -cacy, eff ectiveness, safety and costs of acupunc-ture for chronic pain - results of a large research initiative. Acupunct Med 2006; 24(Supp): S33-9.

Recent Progress in Clinical Research of Acupuncture

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Recent Progress in Clinical Research of Acupuncture

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