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Mediation analysis is a common statistical method used to investigate mechanisms of health exposure and interventions. The reporting quality of mediation studies used in randomised controlled trials has been considered heterogeneous and incomplete. The reporting quality of mediation analysis in observational studies is unknown. We conducted a systematic review to describe the reporting standards of recently published observational studies that used mediation analysis to understand the mechanism of health exposures. We searched for studies published between June 2017 and June 2019 indexed in EMBASE, MEDLINE and PsycINFO. Two reviewers screened articles and selected a random sample of 50 eligible studies for inclusion. We included studies across 13 healthcare fields and ten different health conditions. Most studies (74%) collected data on healthy individuals to assess their risk of developing a health disorder. Psychosocial and behavioural factors (self-control, self-esteem, alcohol consumption, pain) were the most prevalent exposures (n = 30, 60%), outcomes (n = 23, 46%) and mediators (n = 29, 58%). Most studies used a cross-sectional design (64%, n = 32), and a few studies reported sample size calculations (4%, n = 8). In 20% (n = 10) of the studies, adjustment for confounders was reported. Only 10% (n = 5) of studies reported the assumptions underlying the mediation analysis, and 14% (n = 7) of studies conducted some sensitivity analysis to assess the degree which unmeasured confounders would affect the estimate of the mediation effect. Mediation analysis is a common method used to investigate mechanisms in prevention research. The reporting of mediation analysis in observational studies is incomplete and may impact reproducibility, evidence synthesis and implementation.

BACKGROUND: Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.OBJECTIVES: To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.METHODS: The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.MAIN RESULTS: Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention). Muscle relaxants and benzodiazepines There was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57). Opioids There was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26). There was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25). There was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11). Antidepressants There was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29).AUTHORS' CONCLUSIONS: We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

Background Antidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP. Methods We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0–100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason. Results We included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI − 6.15 to − 2.50) on a 0–100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo. Conclusions Treatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP. Trial registration We prospectively registered the protocol for this systematic review on PROSPERO (CRD42020149275).

Refereed/Peer-reviewed Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, Setting, and Participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main Outcomes and Measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P =.001), favoring the intervention group. Conclusions and Relevance: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial Registration: ANZCTR Identifier: ACTRN12615000610538.

Question What are the effects of specific types of exercise treatments on pain intensity and functional limitation outcomes for adults with chronic low back pain? Design Systematic review with network meta-analysis of randomised controlled trials. Participants Adults with non-specific low back pain for ≥ 12 weeks. Intervention Exercise treatments prescribed or planned by a health professional that involved conducting specific activities, postures and/or movements with a goal to improve low back pain outcomes. Outcome measures Pain intensity (eg, visual analogue scale or numerical rating scale) and back-related functional limitations (eg, Roland Morris Disability Questionnaire or Oswestry Disability Index), each standardised to range from 0 to 100. Results This review included 217 randomised controlled trials with 20,969 participants and 507 treatment groups. Most exercise types were more effective than minimal treatment for pain and functional limitation outcomes. Network meta-analysis results were compatible with moderate to clinically important treatment effects for Pilates, McKenzie therapy, and functional restoration (pain only) and flexibility exercises (function only) compared with minimal treatment, other effective treatments and other exercise types. The estimated mean differences for these exercise types compared with minimal treatment ranged from −15 to −19 for pain and from −10 to −12 for functional limitation. Conclusion This review found evidence that Pilates, McKenzie therapy and functional restoration were more effective than other types of exercise treatment for reducing pain intensity and functional limitations. Nevertheless, people with chronic low back pain should be encouraged to perform the exercise that they enjoy to promote adherence. Registration DOI: 10.1002/14651858.CD009790 .

Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference −7.7, 95% confidence interval−12.1 to−3.3) but not a reduction in disability (−3.3, −7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/ .

BackgroundThere is limited evidence for the comparative effectiveness of analgesic medicines for adults with low back pain. This systematic review and network meta-analysis aims to determine the analgesic effect, safety, acceptability, effect on function, and relative rank according to analgesic effect, safety, acceptability, and effect on function of a single course of [an] analgesic medicine(s) or combination of these medicines for people with low back pain.MethodsWe will include published and unpublished randomised trials written in any language that compare an analgesic medicine to either another medicine, placebo/sham, or no intervention in adults with low back pain, grouped according to pain duration: acute (fewer than 6 weeks), sub-acute (6 to 12 weeks), and chronic (greater than 12 weeks). The co-primary outcomes are pain intensity following treatment and safety (adverse events). The secondary outcomes are function and acceptability (all-cause dropouts). We will perform a network meta-analysis to compare and rank analgesic medicines. We will form judgements of confidence in the results using the Confidence in Network Meta-Analysis (CINeMA) methodology.DiscussionThis network meta-analysis will establish which medicine, or combination of medicines, is most effective for reducing pain and safest for adults with low back pain.Systematic review registrationPROSPERO CRD42019145257

Objective To review and assess the methodological quality of randomised controlled trials that test physical therapy interventions for low back pain. Study Design and Setting Systematic review of trials of physical therapy interventions to prevent or treat low back pain (of any duration or type) in participants of any age indexed on the Physiotherapy Evidence Database (PEDro). Existing PEDro scale ratings were used to evaluate methodology quality. Results This review identified 2215 trials. The majority of trials were for adults (n=2136, 96.4%), low back pain without specific aetiology (n=1863, 84.1%), and chronic duration (n=947, 42.8%). The quality of trials improved over time, however most were at risk of bias. Less than half of the trials concealed allocation to intervention (n=813, 36.7%), used intention-to-treat principles (n=778, 35.1%), blinded assessors (n=810, 36.6%), participants (n=174, 7.9%) and therapists (n=39, 1.8%). These findings did not vary by type of therapy. Conclusion The majority of trials that test physical therapy interventions for low back pain have methodological limitations that could bias treatment effect estimates. Greater attention to simple methodological features, such as allocation concealment and the reporting of intention-to-treat effects, would improve the quality of trials testing physical therapy interventions for low back pain.

Background Statistical analysis plans describe the planned data management and analysis for clinical trials. This supports transparent reporting and interpretation of clinical trial results. This paper reports the statistical analysis plan for the RESOLVE clinical trial. The RESOLVE trial assigned participants with chronic low back pain to graded sensory-motor precision training or sham-control. Results We report the planned data management and analysis for the primary and secondary outcomes. The primary outcome is pain intensity at 18-weeks post randomization. We will use mixed-effects models to analyze the primary and secondary outcomes by intention-to-treat. We will report adverse effects in full. We also describe analyses if there is non-adherence to the interventions, data management procedures, and our planned reporting of results. Conclusion This statistical analysis plan will minimize the potential for bias in the analysis and reporting of results from the RESOLVE trial. Trial registration ACTRN12615000610538 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368619 ).

Recently, the degree to which scientific publications provides a reliable source of information has come under intense scrutiny. Reports suggest that a substantial amount of published literature is likely to be biased, distorted, and non-reproducible. This cuts across basic, pre-clinical, and clinical research. It has been estimated that non-reproducible preclinical research consumes $28 billion/year (USD) and that 85% of biomedical research resources are wasted on biased research. The response from the scientific and policy community has been to identify common practices that contribute to the problem, and develop methods to counteract them. This matter is very relevant to the pain field. Understanding the causes of non-reproducible and non-replicable research and its ultimate impact on how we prevent and treat pain should assist pain researchers to improve the reproducibility and replicability of their work. The distinction between reproducibility and replicability is presented in Figure 1 and defined elsewhere. This paper aims to: (1) define drivers of non-reproducible and non-replicable research with examples from pain sciences and broader research fields; and (2) provide an overview of potential solutions and practices that could improve reproducibility and replicability of pain research.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Scientific progress requires transparency and openness. The ability to critique, replicate and implement scientific findings depends on the transparency of the study design and methods, and the open availability of study materials, data and code. Journals are key stakeholders in supporting transparency and openness. This study aimed to evaluate 10 highest ranked pain journals' authorship policies with respect to their support for transparent and open research practices. Two independent authors evaluated the journal policies (as at 27 May 2019) using three tools: the self-developed Transparency and Openness Evaluation Tool, the Centre for Open Science (COS) Transparency Factor and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosure of conflicts of interest. We found that the journal policies had an overall low level of engagement with research transparency and openness standards. The median COS Transparency Factor score was 3.5 (IQR 2.8) of 29 possible points, and only 7 of 10 journals' stated requirements for disclosure of conflicts of interest aligned fully with the ICMJE recommendations. Improved transparency and openness of pain research has the potential to benefit all that are involved in generating and using research findings. Journal policies that endorse and facilitate transparent and open research practices will ultimately improve the evidence base that informs the care provided for people with pain.

As a service to its readership, BJSM publishes educational editorials in order to provide methodological guidance and direction to clinicians and researchers.1 For example, a recent BJSM invited commentary outlined important methodological aspects of randomised controlled trials ( RCTs ) in order to help readers better understand and interpret findings.2 Similarly, a recent BJSM editorial written for clinicians has outlined five essential methodological considerations or ‘hacks’ to consider when reading a systematic review (SR), while another editorial has outlined common pitfalls for authors conducting a SR.3 4 In light of recent suggestions of untrustworthiness of systematic review and meta-analyses (SRMA) findings,5–7 researchers are encouraged to maximise the transparency of their work. Similarly, clinicians and policymakers are encouraged to scrutinise SRMA in order to decide if the findings should influence clinical decisions or policies. The purpose of our two-part educational editorial series is to highlight important methodological aspects of SRMA of the effects of interventions and thus help clinicians make judicious choices when considering whether to accept the findings. By using a worked example, we hope this resource serves as a guide for clinicians when critically appraising SRMA findings and deciding whether (or not) to accept the reported findings or the interpretation of the authors. A SR attempts to collate all empirical evidence that fits prespecified eligibility criteria in order to answer a specific research question.8 An interventional SR specifically assesses the benefits and harms of an intervention and should provide an unbiased, robust, transparent and reproducible overview of the effect of an intervention and the quality of the evidence from identified clinical studies.9 Should the SR contain sufficient and appropriate quantitative data from the included studies, a meta-analysis (MA) can be conducted to provide a pooled estimate of effect, and to examine variation among individual study …

Systematic review and meta-analyses (SRMA) represent the highest quality of evidence of the effects of interventions and have the capacity to usefully inform clinical decisions, reduce research waste and direct policy making.1–4 Interventional SRMA often amalgamate the results of multiple randomised controlled trials (RCTs) to determine the magnitude of the estimate of the effect for a chosen intervention and to examine variation among study outcomes (heterogeneity).5 As such they represent the highest level of evidence to inform clinicians on the usefulness of a given treatment. Of course, the robustness of SRMA findings is dependent on the quality of the trials that have been pooled. The aim of this two-part Educational Editorial Series is to outline a process of scrutiny and analysis for SRMA to facilitate answering the important question ‘Should this SRMA change my practice?’. An understanding of key features of SRMA which have been outlined in related BJSM Educational Editorials is needed by clinicians in order to make this decision.2 6–10 Here, we present a worked example for clinicians illustrating some important considerations when reading an interventional SRMA. Specifically, we highlight the need to consider the pooling of comparators, clinical diversity, comparisons to active control, risk of bias and confidence in the results when interpreting interventional SRMA findings. The example SRMA investigated the efficacy of platelet-rich plasma (PRP) injections for tendinopathy.11 Based on data extracted from 16 RCTs (see online supplementary file 1 for a list of references), the authors reported a moderate treatment effect in favour of PRP with a standard mean difference (SMD) of 0.47 (95% CI 0.22 to 0.72, p

The sacroiliac joint (SIJ) is often considered to be involved when people present for care with low back pain where SIJ is located. However, determining why the pain has arisen can be challenging, especially in the absence of a specific cause such as pregnancy, disease, or trauma, when the SIJ might be identified as a source of symptoms with the help of manual clinical tests. Nonspecific SIJ-related pain is commonly suggested to be causally associated with movement problems in the SIJ(s)—a diagnosis traditionally derived from manual assessment of movements of the SIJ complex. Management choices often consist of patient education, manual treatment, and exercise. Although some elements of management are consistent with guidelines, this Perspective article argues that the assumptions on which these diagnoses and treatments are based are problematic, particularly if they reinforce unhelpful, pathoanatomical beliefs. This article reviews the evidence regarding the clinical detection and diagnosis of SIJ movement dysfunction. In particular, it questions the continued use of assessing movement dysfunction despite mounting evidence undermining the biological plausibility and subsequent treatment paradigms based on such diagnoses. Clinicians are encouraged to align their assessment methods and explanatory models with contemporary science to reduce the risk of their diagnoses and choice of intervention negatively affecting clinical outcomes.

Objective: Systematic reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n = 5 individual source systematic reviews. We reproduced the meta-analyses using data available from the original reviews and then reran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared with sham, for recent-onset low back pain from −21.71 (95% CI: −28.23 to −15.19) to −2.34 (95% CI: −3.34 to −1.34) on a 0–100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared with sham, for chronic low back pain from −10.10 (95% CI: −12.81 to −7.39) to −9.31 (95% CI: −11.51 to −7.11). The effect reduced in the subgroup of enriched design studies, from −12.40 (95% CI: −16.90 to −7.91) to −11.34 (95% CI: −15.36 to −7.32), and in the subgroup of nonenriched design studies, from −7.27 (95% CI: −9.97 to −4.57) to −7.19 (95% CI: −9.24 to −5.14). Conclusion: Systematic reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful. Refereed/Peer-reviewed

Background Exercise is recommended for the management of chronic low back pain (CLBP). Trialists have proposed numerous mechanisms to explain why exercise improves pain and function in people with CLBP, but these are yet to be synthesised. Objective To synthesise the proposed mechanisms of benefit for exercise in people with CLBP. Design Review. Methods The Physiotherapy Evidence Database (PEDro) was searched from inception to July 2019. Randomised controlled trials of adults with CLBP, indexed in PEDro as ‘fitness training’, were included. Two reviewers independently screened and extracted data from each study. Data were analysed quantitatively and qualitatively using thematic analysis. Results 186 studies were identified and 110 were included in the analysis. Thirty-six studies (33%) did not provide a mechanism of benefit for exercise in people with CLBP. Of the remaining studies, most provided more than one mechanism, from which 33 unique mechanisms were identified. These were grouped into five themes which, from most to least common, were: neuromuscular (n = 105 (44%)); psychosocial (n = 87 (36%)); neurophysiological (n = 22 (9%)); cardiometabolic (n = 15 (6%)); and tissue healing (n = 12 (5%)). The effects of these proposed mechanisms on outcomes for people with CLBP were seldom examined. Conclusions This review identified a variety of mechanisms proposed in clinical trials to explain why ‘fitness training’ works for people with CLBP, but these mechanisms were seldom tested. Randomised controlled trials investigating the mediating effects of these mechanisms may be warranted to better understand why exercise works for CLBP.

The recent network meta-analysis by Owen and colleagues1 included 89 trials of exercise for chronic low back pain (LBP) and reported low quality evidence that Pilates, stabilisation, resistance and aerobic exercises are the most effective treatments for these patients. We were surprised by how few trials were included and even more surprised by how large the estimates of treatment effect were. For example, with Pilates the effect is reported to be 1.86 standardised mean difference (SMD) in the abstract and 2.32 SMD in online supplementary table 5. These estimates are about 3–4 times effect sizes normally reported for exercise interventions in LBP and so we took a closer look at the review to try to understand what had happened. That investigation revealed some important issues that we would like to share with readers. First, the review has missed a lot of relevant trials. The Cochrane review of exercise for chronic LBP that is currently underway has identified over 350 trials, whereas the Owen review included only 89. Even applying the restrictive selection criteria of the Owen …

Low back pain (LBP) has a significant impact on the sufferer and society as a whole. Therefore, we read with great interest the Specific Treatment of Problems of the Spine (STOPS) trial1 suggesting that an individualised physiotherapy approach had a favourable outcome when compared with advice in a cohort of participants with LBP lasting for more than 6 weeks. These findings highlight important issues in the design and subsequent interpretation of randomised controlled trials (RCTs) in this area. The primary purpose of RCTs is to determine if an intervention meaningfully improves clinical outcomes. This is realised by comparing the intervention with an appropriate control.2 To determine efficacy, the ideal control is a credible placebo, but this is often difficult to design for non-pharmacological treatments. Thus, an alternative intervention is frequently used as the control. This design does not estimate efficacy; rather, it compares whether one approach is superior to another. Therefore, it is possible for an intervention to be deemed effective when compared with a control for which outcomes are suboptimal. This is relevant in LBP clinical trials and in other …

Persistent low back pain (LBP) is the leading cause of disability globally, for which ever-larger increases in healthcare expenditure have not made a difference in terms of prevalence or burden.1 It is unquestionable that current healthcare is failing individuals with chronic LBP, and we contend that recent evidence from the interventional pain medicine field points clearly to what these failings are. There has been remarkable growth in the use of interventional pain medicine procedures to manage chronic LBP, particularly radiofrequency denervation.2 In this approach, various diagnostic practices are used to identify a peripheral ‘nociceptive driver’, with the presumption that denervation of the peripheral structure will eradicate or significantly reduce pain and improve function.3 The growth in the use of radiofrequency denervation is surprising given that, until recently, the evidence base was equivocal2 and based on conflicting results from a limited number of small trials. A welcome addition to the field was recently provided by Juch et al ,2 who reported on the outcome of three large clinical trials of neuroablative procedures in chronic LBP. All three trials compared guideline-based physical rehabilitation to rehabilitation with the addition of radiofrequency denervation. Despite employing a …

© 2016 Australian Physiotherapy Association Introduction Low back pain is the leading worldwide cause of disability, and results in significant personal hardship. Most available treatments, when tested in high-quality randomised, controlled trials, achieve only modest improvements in pain, at best. Recently, treatments that target central nervous system function have been developed and tested in small studies. Combining treatments that target central nervous system function with traditional treatments directed towards functioning of the back is a promising approach that has yet to be tested in adequately powered, prospectively registered, clinical trials. The RESOLVE trial will be the first high-quality assessment of two treatment programs that combine central nervous system-directed and traditional interventions in order to improve chronic low back pain. Aim To compare the effectiveness of two treatment programs that combine central nervous system-directed and traditional interventions at reducing pain intensity at 18 weeks post randomisation in a randomised clinical trial of people with chronic low back pain. Design Two-group, randomised, clinical trial with blinding of participants and assessors. Participants and setting Two hundred and seventy-five participants with chronic low back pain that has persisted longer than 3 months and no specific spinal pathology will be recruited from the community and primary care in Sydney, Australia. Interventions Both of the interventions contain treatments that target central nervous system function combined with treatments directed towards functioning of the back. Adherence to the intervention will be monitored using an individual treatment diary and adverse events recorded through passive capture. Participants are informed prior to providing informed consent that some of the treatments are not active. Blinding is maintained by not disclosing any further information. Complete disclosure of the contents of the intervention has been made with the UNSW HREC (HC15357) and an embargoed project registration has been made on the Open Science Framework to meet the Declaration of Helsinki requirement for transparent reporting of trial methods a priori. Intervention A Participants randomised to Intervention A will receive a 12-session treatment program delivered as 60-minute sessions, scheduled approximately weekly, over a period of 12 to 18 weeks. All treatment sessions are one-on-one. The program includes a home treatment component of 30 minutes, five times per week. The intervention comprises discussion of the participant's low back pain experience, graded sensory training, graded motor imagery training and graded, precision-focused and feedback-enriched, functional movement training. Treatment progression is determined by participant proficiency, with mandatory advancement at set time points with respect to a standard protocol. Intervention B Participants randomised to Intervention B will receive a 12-session treatment program of the same duration and structure as Intervention A. The intervention comprises discussion of the participant's low back pain experience, transcranial direct current stimulation to the motor and pre-frontal cortices, cranial electrical stimulation, and low-intensity laser therapy and pulsed electromagnetic energy to the area of greatest pain. Treatment is delivered according to published recommendations and progressed with respect to a standard protocol. Measurements The primary outcome is pain intensity at 18 weeks post randomisation. Secondary outcomes will include disability, depression, pain catastrophising, kinesiophobia, beliefs about back pain, pain self-efficacy, quality of life, healthcare resource use, and treatment credibility. Assessment will occur at baseline and at 18, 26 and 52 weeks after randomisation. Treatment credibility will be assessed at baseline and 2 weeks after randomisation only. Analysis A statistician blinded to group status will analyse the data by intention-to-treat using linear mixed models with random intercepts. Linear contrasts will be constructed to compare the adjusted mean change (continuous variables) in outcome from baseline to each time point between intervention A and intervention B. This will provide effect estimates and 95% confidence intervals for any difference between the interventions. Significance Preliminary data suggest that combining treatments that target central nervous system function with traditional interventions is a promising approach to chronic low back pain treatment. In the context of modest effects on pain intensity from most available treatments, this approach may lead to improved clinical outcomes for people with chronic low back pain. The trial will determine which, if either, of two treatment programs that combine central nervous system-directed and traditional interventions is more effective at reducing pain intensity in a chronic low back pain cohort. Central nervous system-directed interventions constitute a completely new treatment paradigm for chronic low back pain management. The results have the potential to be far reaching and change current physiotherapy management of chronic low back pain in Australia and internationally.