Long term benefits of acupuncture for chronic pain: what makes a difference? Hugh MacPherson www.hughmacpherson.com 1
Outline 1. Acupuncture for chronic pain the Acupuncture Trialists Collaboration, and long-term effects 2. Longer-term effects of acupuncture from trials conducted in the UK 3. Exploring explanation of longer term effects in the ATLAS chronic neck pain trial 2
J.-S. Han, Y.-S. Ho / Neuroscience and Biobehavioral Reviews 35 (2011) 680 687
1.1. Members of the Acupuncture Trialists Collaboration www.acupuncturetrialistscollaboration.org 4
Methods: We combined 29 high quality acupuncture trials in a single database with 17,922 patients with chronic pain: Aims: Acupuncture trialists collaboration Osteoarthritis Headache/migraine Low back and neck pain 1. Establish effect of acupuncture vs. usual/standard care 2. Establish effect of acupuncture vs. sham 3. Establish long term trajectory of benefit www.acupuncturetrialistscollaboration.org 5
Individual patient data meta-analysis Single database with raw data obtained from 29 trials with 17,922 patients: 20 trials with sham controls (5,230 patients) 18 trials with usual/standard care controls (14,597 patients) NB: some trials had three arms
Is acupuncture better than sham Acupuncture, varies across trials Sham acupuncture controls vary: Non-needle sham (e.g. inactive TENS) Needle-based sham Penetrating needles Non-penetrating needle At acupuncture points At non-acupuncture points
Individual patient data meta-analysis Acupuncture vs. Sham controls (n= 5,230) Indication Effect size (Fixed effects) Acupuncture vs. Sham controls (excluding outliers) Migraine/headache -0.15 (-0.24, -0.07) P<0.001 Osteoarthritis -0.16 (-0.25, -0.07) P<0.001 LBP & Neck Pain -0.23 (-0.33, -0.13) P<0.001 Interpretation of effect sizes: 0.8 = LARGE 0.5 = MODERATE 0.3 = SMALL Negative values represent better outcomes Values in parentheses are 95% confidence intervals
Is acupuncture better than nonacupuncture controls Acupuncture, varies across trials Non-acupuncture controls vary: No treatment Wait list Attention control Rescue medication Usual care Other standard treatment
Individual patient data meta-analysis Acupuncture vs. Sham controls, and Acupuncture vs. Non-acupuncture controls (n= 14,597 ) Indication Effect size (Fixed effects) Acupuncture vs. Sham controls (excluding outliers) Migraine/headache -0.15 (-0.24, -0.07) P<0.001 Osteoarthritis -0.16 (-0.25, -0.07) P<0.001 Back & Neck Pain -0.23 (-0.33, -0.13) P<0.001 Acupuncture vs. Non-acupuncture controls Migraine/headache -0.42 (-0.46, -0.37) P<0.001 Osteoarthritis -0.57 (-0.64, -0.50) P<0.001 Back & Neck Pain -0.55 (-0.58, -0.51) P<0.001 Negative values represent better outcomes Values in parentheses are 95% confidence intervals Effect sizes: 0.8 = LARGE 0.5 = MODERATE 0.3 = SMALL
Summary of findings: Effect size of acupuncture vs. usual care = 0.5 Effect size of acupuncture vs. sham acupuncture = 0.2 Effect size of sham acupuncture plus context vs. usual care = 0.3 Effect sizes: LARGE = 0.8 MODERATE = 0.5 SMALL = 0.3 All statistically significant : P<0.001
Acupuncture provides an additional 40% benefit over and above sham (placebo) Effect size 0.6 Effect sizes: 0.8 = Large 0.5 = Moderate 0.5 0.3 = Small 0.4 0.3 0.2 0.1 0 Acup vs. usual care 40% 60% Effect size Acupuncture vs. sham Sham acupuncture plus context effects vs. usual care
Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo.. (a result) that can be distinguished from bias. Vickers et al. Archives of Internal Medicine. 2012, 172 (19): pp.1444-1453
ATC trials: Acupuncture vs. usual care Trajectory: ~10% of the benefit of acupuncture relative to usual care is lost at 12 months Thicker line = 5 trials or more MacPherson et al. PAIN. In press 2016
ATC trials: Acupuncture vs. sham ATC trials: Acupuncture vs. usual care Trajectory: ~50% of the benefit of acupuncture vs. sham controls is lost at 12 months Thicker line = 10 trials or more MacPherson et al. PAIN. In press 2016
Why inconsistency with other reviews? What at sample sizes? Estimated effect size Approx sample size* for a twoarm trial Medium 0.5 170 Small 0.3 468 Effect sizes: 0.8 = Large 0.5 = Moderate 0.3 = Small *Number needed to show a difference, if one existed, based on 90% power and 0.05 significance
Why inconsistency with other reviews? Sample sizes too small Estimated effect size Approx sample size* for a twoarm trial Medium 0.5 170 Small 0.3 468 True vs. sham acupuncture 0.2 1,052 Effect sizes: 0.8 = Large 0.5 = Moderate 0.3 = Small *Number needed to show a difference, if one existed, based on 90% power and 0.05 significance
Researching acupuncture Acupuncture as simple or complex? Acupuncture can be defined in two contrasting ways Simple intervention: Insertion of needles Complex intervention: A package of care Different mechanisms
Pragmatic trials for complex interventions. Randomised, controlled Typically usual/standard care is comparator Assessing comparative effectiveness Routine care context Practitioners can provide treatments that reflect their everyday practice Results are more generalisable Relevant for cost- effectiveness Decision making 19
2. Pragmatic trials from the UK n date Headache and migraine 401 2004 Chronic back pain 241 2006 Irritable bowel syndrome 233 2012 Depression 755 2013 Chronic neck pain 517 2015
40 Headache and migraine (n=401) Acupuncture for chronic headache/migraine Acupuncture Usual care 20 Diff = 3.9 pts P=0.001 Diff = 4.6 pts P=0.002 0 Baseline 3 months 12 months Vickers et al BMJ 2004
Acupuncture for low back pain vs. usual care 100= no pain Low back pain (n=241) Thomas et al BMJ 2006; 333: 623-626 22
Irritable bowel syndrome (n=233) Acupuncture for irritable bowel syndrome 23 MacPherson et al. BMC Gastroenterology 2012, 12:150
Depression (n=755) MacPherson et al. PLoS Medicine, 2013, 10 (9): e 1001518 24
Headache /migraine Long-term effects Low back pain Irritable bowel Depression 25
Components of routine acupuncture Specific components integral to treatment include: Acupuncture-related diagnosis Explanations of the diagnosis Needling of points Diagnosis-related lifestyle advice given Patient take-up of lifestyle advice NB: Specific because theory-related and designed to impact on outcome 26
3. Case study: Acupuncture for chronic neck pain (ATLAS trial) 1. Is acupuncture clinically effective compared to usual care? 2. Is Alexander technique clinically effective compared to usual care? Secondary research questions: Life-style advice given? Why? Is it acted upon? Does self-efficacy increase with treatment? Do changes in self-efficacy reduce pain? 27
Trial Flow Chart Assessed 1,144 patients Randomly allocated 517 Acupuncture 173 (33%) Alexander 172 (33%) Usual GP Care 172 (33%) 3 month 3 month 3 month 20 SMS follow ups 6 month 6 month 6 month Questionnaire follow ups Practitioner focus group 12 month 12 month Analysis 12 month Patient interviews at 3 and 12 months 28
Design Patient eligibility criteria: 18 years of age and over Diagnosed with neck pain by GP Baseline score 28 or above on NPQ (Northwick Park neck pain & disability Questionnaire) Exclusion criteria: currently receiving acupuncture/alexander terminal illness, transmissible blood disorder serious underlying pathology 29
The acupuncture Acupuncture Up to 12 sessions, mostly weekly, approx 50 minutes Individualised needling and acupuncture diagnosisrelated lifestyle and self-care advice Active engagement of patient if possible Members of British Acupuncture Council (BAcC) 3 years post qualification experience
Outcomes Questionnaire data collected from patients at baseline, 3, 6 and 12 months Primary outcome measure: Northwick Park neck pain and disability Questionnaire (NPQ) Primary end-point at 12 months Secondary outcome measures include: Lifestyle advice Chronic Pain Self-Efficacy Scale 31
Recruitment: Participants Recruitment from 33 general medical practices in York, Manchester, Leeds and Sheffield, UK Baseline characteristics: Predominantly female (70%) Mean age 53 In paid employment (61%) Duration of neck pain (6 years) Taking prescription medication (76%) 32
Acupuncture provided Characteristics of the acupuncture 18 acupuncturists, average 15 years in practice Average 7 patients per practitioner Average 11 treatments per patient Practitioners completed logbooks documenting: Diagnosis and treatment Lifestyle advice & rationale 33
Raw outcome data (n=517) Acupuncture or Alexander lessons vs. usual care Unadjusted neck pain (NPQ) scores over 12 months MacPherson et al. Annals of Internal Medicine, 2015 34
Acupuncture log-book data Lifestyle advice: 134 patients (84%) received advice Advised lifestyle change No. patients given advice % no. patients use on who received advice (n=134) Exercise 72 54% Relaxation 59 44% Diet 54 40% Rest 47 35% Work 31 23% Other 29 22% 35
Acupuncture log-book data Relationship between advice and diagnosis Advice given Rationale for patients with Liver-related diagnosis Rationale for patients with Spleen diagnosis Exercise To move Liver Qi N=67 (93%) To tonify Spleen Qi N=2 (3%) Relaxation To soothe Liver N=33 (56%) To conserve Qi N=12 (20%) Diet To reduce Liver Heat N=17 (31%) To tonify Spleen Qi clear Damp N=34 (63%) Rest To relax Liver N=8 (17%) To conserve Qi N=24 (51%) Work To sedate Liver N=16 (52%) To conserve Qi N=3 (10%) 36
Patient reported variables Better outcomes for acupuncture compared to usual care at 6 months associated with: Changes made in exercise, relaxation, diet or rest Number of lifestyle changes made Extent advice was put into practice Ability to make improvements in self-care Extent changes perceived as helpful [All P<0.005]
Chronic Pain Self-Efficacy Scale 38
Patient reported self-efficacy In the acupuncture group (and Alexander group) compared to the usual care group, we found: Change in self efficacy at 6 months greater in the acupuncture group (P<0.0002) Better self-efficacy associated with: Reduced pain scores at 6 months (P<0.0004) Reduced pain scores at 12 months (P<0.0004) 39
Implications for acupuncture and research Acupuncture is beneficial in reducing chronic pain effect size is moderate (~0.5) 90% of effect sustained at 12 months Acupuncture is more than a placebo effect size is small (~0.2) a result that is not due to bias Trials need a large enough sample size to have sufficient power 40
Implications for acupuncture and research Pragmatic trials are relevant for the evaluation of routine care Trials need to document life-style advice and measure long-term outcomes Lifestyle advice related to diagnosis can improve self-efficacy related to pain Improved self-efficacy can reduce pain over the longer term 41
ATC publications to date: 1. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Victor N, et al. Individual patient data meta-analysis of acupuncture for chronic pain: protocol of the Acupuncture Trialists Collaboration. Trials. 2010;11:90. 2. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE, et al. Acupuncture for Chronic Pain: Individual Patient Data Meta-analysis. ArchInternMed. 2012 Sep 10;172(19):1444 53. 3. Vickers AJ, Maschino AC, Lewith G, MacPherson H, Sherman KJ, Witt CM, et al. Responses to the Acupuncture Trialists Collaboration individual patient data metaanalysis. Acupunct Med. 2013 Mar;31(1):98 100. 4. MacPherson H, Maschino AC, Lewith G, Foster NE, Witt C, Vickers AJ, et al. Characteristics of acupuncture treatment associated with outcome: an individual patient meta-analysis of 17,922 patients with chronic pain in randomised controlled trials. PLoS ONE. 2013;8(10):e77438. 5. MacPherson H, Vertosick E, Lewith G, Linde K, Sherman KJ, Witt CM, et al. Influence of Control Group on Effect Size in Trials of Acupuncture for Chronic Pain: A Secondary Analysis of an Individual Patient Data Meta-Analysis. PLoS ONE. 2014 Apr 4;9 (4):e93739. 6. Vickers AJ, Linde K. Acupuncture for chronic pain. JAMA. 2014 Mar 5;311(9):955 6. 7. MacPherson H, Vertosick E, Foster N, Lewith G, Linde, K, Sherman K, Witt C, Vickers A. The persistence of the effects of acupuncture after a course of treatment. In Press with PAIN.
Pragmatic trials with long-term outcomes 1. Vickers AJ, Rees RW, Zollman CE, McCarney R, Smith CM, Ellis N, et al. Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial. BMJ. 2004;328(1468-5833):744. 2. Thomas KJ, MacPherson H, Thorpe L, Brazier J, Fitter M, Campbell MJ, et al. Randomised controlled trial of a short course of traditional acupuncture compared with usual care for persistent non-specific low back pain. BMJ. 2006 Sep 23;333:623 6. 3. MacPherson H, Tilbrook H, Bland JM, Bloor K, Brabyn S, Cox H, et al. Acupuncture for irritable bowel syndrome: primary care based pragmatic randomised controlled trial. BMC Gastroenterol. 2012;12:150. 4. MacPherson H, Richmond S, Bland M, Brealey S, Gabe R, Hopton A, et al. Acupuncture and Counselling for Depression in Primary Care: A Randomised Controlled Trial. PLoS Medicine. 2013 Sep 24;10(9):e1001518. 5. MacPherson H, Tilbrook H, Richmond S, Woodman J, Ballard K, Atkin K, et al. Alexander Technique Lessons or Acupuncture Sessions for Persons With Chronic Neck Pain: A Randomized Trial. Ann. Intern. Med. 2015 Nov 3;163(9):653 62. 43