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      Acupuncture for the Relief of Chronic Pain: A Synthesis of Systematic Reviews

      review-article
      1 , 2 , * , 2
      Medicina
      MDPI
      acupuncture, pain, systematic review, evidence synthesis

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          Abstract

          Background and Objectives: It is estimated that 28 million people in the UK live with chronic pain. A biopsychosocial approach to chronic pain is recommended which combines pharmacological interventions with behavioural and non-pharmacological treatments. Acupuncture represents one of a number of non-pharmacological interventions for pain. In the current climate of difficult commissioning decisions and constantly changing national guidance, the quest for strong supporting evidence has never been more important. Although hundreds of systematic reviews (SRs) and meta-analyses have been conducted, most have been inconclusive, and this has created uncertainty in clinical policy and practice. There is a need to bring all the evidence together for different pain conditions. The aim of this review is to synthesise SRs of RCTs evaluating the clinical efficacy of acupuncture to alleviate chronic pain and to consider the quality and adequacy of the evidence, including RCT design. Materials and Methods: Electronic databases were searched for English language SRs and meta-analyses on acupuncture for chronic pain. The SRs were scrutinised for methodology, risk of bias and judgement of efficacy. Results: A total of 177 reviews of acupuncture from 1989 to 2019 met our eligibility criteria. The majority of SRs found that RCTs of acupuncture had methodological shortcomings, including inadequate statistical power with a high risk of bias. Heterogeneity between RCTs was such that meta-analysis was often inappropriate. Conclusions: The large quantity of RCTs on acupuncture for chronic pain contained within systematic reviews provide evidence that is conflicting and inconclusive, due in part to recurring methodological shortcomings of RCTs. We suggest that an enriched enrolment with randomised withdrawal design may overcome some of these methodological shortcomings. It is essential that the quality of evidence is improved so that healthcare providers and commissioners can make informed choices on the interventions which can legitimately be provided to patients living with chronic pain.

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          New evidence pyramid

          A pyramid has expressed the idea of hierarchy of medical evidence for so long, that not all evidence is the same. Systematic reviews and meta-analyses have been placed at the top of this pyramid for several good reasons. However, there are several counterarguments to this placement. We suggest another way of looking at the evidence-based medicine pyramid and explain how systematic reviews and meta-analyses are tools for consuming evidence—that is, appraising, synthesising and applying evidence.
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            The Impact of Study Size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews

            Background Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results. Methods and Findings For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ≥50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range −1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease. Conclusions When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.
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              Size is everything--large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects.

              Variability in patients' response to interventions in pain and other clinical settings is large. Many explanations such as trial methods, environment or culture have been proposed, but this paper sets out to show that the main cause of the variability may be random chance, and that if trials are small their estimate of magnitude of effect may be incorrect, simply because of the random play of chance. This is highly relevant to the questions of 'How large do trials have to be for statistical accuracy?' and 'How large do trials have to be for their results to be clinically valid?' The true underlying control event rate (CER) and experimental event rate (EER) were determined from single-dose acute pain analgesic trials in over 5000 patients. Trial group size required to obtain statistically significant and clinically relevant (0.95 probability of number-needed-to-treat within -/+0.5 of its true value) results were computed using these values. Ten thousand trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to random chance alone. Most common analgesics have EERs in the range 0.4-0.6 and CER of about 0.19. With such efficacy, to have a 90% chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30-60. For clinical relevance nearly 500 patients are required in each group. Only with an extremely effective drug (EER > 0.8) will we be reasonably sure of obtaining a clinically relevant NNT with commonly used group sizes of around 40 patients per treatment arm. The simulated trials showed substantial variation in CER and EER, with the probability of obtaining the correct values improving as group size increased. We contend that much of the variability in control and experimental event rates is due to random chance alone. Single small trials are unlikely to be correct. If we want to be sure of getting correct (clinically relevant) results in clinical trials we must study more patients. Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional (small) size.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                24 December 2019
                January 2020
                : 56
                : 1
                : 6
                Affiliations
                [1 ]Research and Development Dept, Airedale National Health Service (NHS) Foundation Trust, Skipton Road, Steeton, Keighley BD20 6TD, UK
                [2 ]Centre for Pain Research, School of Clinical and Applied Sciences, Leeds Beckett University, City Campus, Leeds LS1 3HE, UK; M.Johnson@ 123456leedsbeckett.ac.uk
                Author notes
                [* ]Correspondence: carole.paley@ 123456nhs.net
                Author information
                https://orcid.org/0000-0002-6335-2666
                https://orcid.org/0000-0002-9421-9622
                Article
                medicina-56-00006
                10.3390/medicina56010006
                7023333
                31878346
                462c8f6c-7b32-44e1-b2e4-2b7ceae10163
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 October 2019
                : 06 December 2019
                Categories
                Review

                acupuncture,pain,systematic review,evidence synthesis
                acupuncture, pain, systematic review, evidence synthesis

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