'Which treatment do you believe you received?' A randomised blinding feasibility trial of spinal manual therapy

Muñoz Laguna J., Lee H., Poltavskiy E., Kim J., Bang H.

Gevers-Montoro C., Romero-Santiago B., Medina-García I., Larranaga-Arzamendi B., Álvarez-Gálovich L., Ortega-De Mues A., Piché M.

Chronic primary low back pain (CPLBP) refers to low back pain that persists over 3 months, that cannot be explained by another chronic condition, and that is associated with emotional distress and disability. Previous studies have shown that spinal manipulative therapy (SMT) is effective in relieving CPLBP, but the underlying mechanisms remain elusive. This randomized placebo-controlled dual-blind mixed experimental trial (NCT05162924) aimed to investigate the efficacy of SMT to improve CPLBP and its underlying mechanisms. Ninety-eight individuals with CPLBP and 49 controls were recruited. Individuals with CPLBP received SMT (n = 49) or a control intervention (n = 49), 12 times over 4 weeks. The primary outcomes were CPLBP intensity (0-100 on a numerical rating scale) and disability (Oswestry Disability Index). Secondary outcomes included pressure pain thresholds in 4 body regions, pain catastrophizing, Central Sensitization Inventory, depressive symptoms, and anxiety scores. Individuals with CPLBP showed widespread mechanical hyperalgesia (P < .001) and higher scores for all questionnaires (P < .001). SMT reduced pain intensity compared with the control intervention (mean difference: -11.7 [95% confidence interval, -11.0 to -12.5], P = .01), but not disability (P = .5). Similar mild to moderate adverse events were reported in both groups. Mechanical hyperalgesia at the manipulated segment was reduced after SMT compared with the control intervention (P < .05). Pain catastrophizing was reduced after SMT compared with the control intervention (P < .05), but this effect was not significant after accounting for changes in clinical pain. Although the reduction of segmental mechanical hyperalgesia likely contributes to the clinical benefits of SMT, the role of pain catastrophizing remains to be clarified. PERSPECTIVE: This randomized controlled trial found that 12 sessions of SMT yield greater relief of CPLBP than a control intervention. These clinical effects were independent of expectations, and accompanied by an attenuation of hyperalgesia in the targeted segment and a modulation of pain catastrophizing.

Muñoz Laguna J., Kurmann A., Hofstetter L., Nyantakyi E., Clack L., Bang H., Foster N.E., Braun J., Puhan M.A., Farshad M., Hincapié C.A.

Abstract Introduction Blinding is a methodologically important aspect in randomised controlled trials yet frequently overlooked in trials of spinal manual therapy interventions for back pain. To help inform the blinding methods of a future, double-placebo-controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain, we set four objectives: (1) to assess the feasibility of blinding participants, randomly allocated to an active or placebo-control spinal manual therapy intervention protocol, (2) to assess the feasibility of blinding outcome assessors within the trial, (3) to explore the influence of spinal manual therapy experience and low back pain on blinding, and (4) to explore factors contributing to perceptions about intervention assignment among participants and outcome assessors. Methods and analysis Two-parallel-group, single-centre, placebo-controlled, methodological blinding feasibility randomised trial. We will recruit between 60 and 100 adults with or without back pain and with or without experience of spinal manual therapy from Zurich, Switzerland. Participants will be randomised to either an active spinal manual therapy or a placebo-control spinal manual therapy protocol—both interventions delivered over two study visits, up to two weeks apart. The primary outcome is participant blinding using the Bang blinding index within each intervention arm immediately after each of the two study visits. Secondary outcomes are participant blinding using the James blinding index, outcome assessor blinding (Bang and James blinding indices), self-reported factors influencing perceived intervention assignment among participants and outcome assessors, and participant-reported credibility and expectancy of study interventions. Other outcomes—included to blind the study objective from participants—are lumbar spine range of motion, self-rated general health, satisfaction with care, pain intensity, and function. Intervention provider outcomes include intervention component fidelity and quality of intervention delivery. Ethics and dissemination The independent ethics commission of Canton Zurich granted ethical approval for this study (KEK 2023–00381). Written informed consent will be obtained from all participants. Findings will be disseminated in scientific conferences and a peer-reviewed publication and inform the blinding methods of a future double-placebo controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain—the SALuBRITY trial. Trial registration NCT05778396.

Muñoz Laguna J., Nyantakyi E., Bhattacharyya U., Blum K., Delucchi M., Klingebiel F.K., Labarile M., Roggo A., Weber M., Radtke T., Puhan M.A., Hincapié C.A.

Abstract Study design Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. Background Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. Methods On 7–8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from –1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating ‘random guessing’—balanced ‘active’ and ‘control’ perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. Results 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, −0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (−0.12 to 0.30) and −0.10 (−0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. Conclusions Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. Trial registration ClinicalTrials.gov: NCT05822947 (retrospectively registered)

Ryf C., Hofstetter L., Clack L., Hincapié C.A.

Abstract Background Spinal manual therapy and corticosteroid nerve root injection are commonly used to treat patients with lumbar radiculopathy. The SALuBRITY trial—a two parallel group, double sham controlled, randomised clinical trial—is being developed to compare their effectiveness. By gathering patients’ and clinicians’ perspectives and involving them in discussions related to the trial research question and objectives, proposed trial recruitment processes, methods, and outcome measures, we aimed to improve the relevance and quality of the SALuBRITY trial. Methods We involved patients with lived experience of lumbar radiculopathy (n = 5) and primary care clinicians (n = 4) with experience in the treatment of these patients. Involvement activities included an initial kick-off event to introduce the project, establishing a shared purpose statement, and empowering patient and clinician advisors for their involvement, followed by semi-structured group and individual interviews, and questionnaires to evaluate the experience throughout the project. Results Both patient and clinician advisors endorsed the significance and relevance of the trial’s objectives. Patients assessed the proposed trial methods as acceptable within the context of a trusting patient-clinician relationship. A trial recruitment and enrolment target time of up to five days was regarded as acceptable, although patients with chronic radiculopathy may need more time to consider their trial participation decision. All advisors reached consensus on the acceptability of a medication washout phase of 12- to 24-h before pain outcome measurement, with the inclusion of a rescue medication protocol. Both advisory groups preferred leg pain over back pain as the primary clinical outcome, with patient advisors advocating for personalized primary pain localization. Furthermore, patients requested expanding the pain, enjoyment, and general activity scale with peak pain intensity, rather than average pain alone. Patient and clinician advisors evaluated their engagement in clinical research as meaningful and impactful. Conclusion Patient and public involvement resulted in important and relevant considerations for the SALuBRITY trial, spanning all research phases. These findings hold promise for enhancing the trial’s quality and relevance and improving its translation into clinical practice.

Hohenschurz‐Schmidt D., Phalip J., Chan J., Gauhe G., Soliman N., Vollert J., Lunde S.J., Vase L.

AbstractBackgroundThe magnitude of placebo effects from physical and psychological ‘sham’ is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three‐armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in ‘sham’ control intervention and non‐exposure arms.MethodsRCTs with treatment, ‘sham’ control intervention, and non‐exposure groups were included, enrolling adults with any pain. A protocol was pre‐registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta‐analysis of pain measures at short‐, medium‐ and long‐term was performed with random‐effects models of standardised mean differences (SMD).Studies were sub‐grouped according to control intervention type.ResultsSeventeen RCTs were included. The average short‐term placebo effect was small (0.21 SMD, 0.1–0.33 95% CI, p = 0.0002, 1440 participants). It showed no heterogeneity (Tau2 = 0.1, I2 = 11%, p = 0.3), preventing meta‐regression analyses of effect modifiers. However, sub‐group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments’ short‐term effectiveness. No placebo effects were found at medium‐term (7 RCTs, 381 participants) or long‐term follow‐up (3 RCTs, 173 participants).ConclusionsThe observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long‐term studies and sample heterogeneity.SignificanceThis systematic review directly quantifies placebo effects from physical and psychological ‘sham’ control interventions and compares them to treatments’ overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.

Hohenschurz-Schmidt D., Vase L., Scott W., Annoni M., Ajayi O.K., Barth J., Bennell K., Berna C., Bialosky J., Braithwaite F., Finnerup N.B., Williams A.C., Carlino E., Cerritelli F., Chaibi A., et. al.

Control interventions (often called “sham,” “placebo,” or “attention controls”) are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers’ decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour.

Reid E., Kamlin O.F., Orsini F., De Paoli A.G., Clark H.W., Soll R.F., Carlin J.B., Davis P.G., Dargaville P.A.

Background: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed. Methods: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated. Results: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm. Conclusion: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.

Nguyen C., Boutron I., Zegarra-Parodi R., Baron G., Alami S., Sanchez K., Daste C., Boisson M., Fabre L., Krief P., Krief G., Lefèvre-Colau M., Rannou F.

Osteopathic manipulative treatment (OMT) is frequently offered to people with nonspecific low back pain (LBP) but never compared with sham OMT for reducing LBP-specific activity limitations.To compare the efficacy of standard OMT vs sham OMT for reducing LBP-specific activity limitations at 3 months in persons with nonspecific subacute or chronic LBP.This prospective, parallel-group, single-blind, single-center, sham-controlled randomized clinical trial recruited participants with nonspecific subacute or chronic LBP from a tertiary care center in France starting February 17, 2014, with follow-up completed on October 23, 2017. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 22, 2018, to December 5, 2018.Six sessions (1 every 2 weeks) of standard OMT or sham OMT delivered by nonphysician, nonphysiotherapist osteopathic practitioners.The primary end point was mean reduction in LBP-specific activity limitations at 3 months as measured by the self-administered Quebec Back Pain Disability Index (score range, 0-100). Secondary outcomes were mean reduction in LBP-specific activity limitations; mean changes in pain and health-related quality of life; number and duration of sick leaves, as well as number of LBP episodes at 12 months; and consumption of analgesics and nonsteroidal anti-inflammatory drugs at 3 and 12 months. Adverse events were self-reported at 3, 6, and 12 months.Overall, 200 participants were randomly allocated to standard OMT and 200 to sham OMT, with 197 analyzed in each group; the median (range) age at inclusion was 49.8 (40.7-55.8) years, 235 of 394 (59.6%) participants were women, and 359 of 393 (91.3%) were currently working. The mean (SD) duration of the current LBP episode was 7.5 (14.2) months. Overall, 164 (83.2%) patients in the standard OMT group and 159 (80.7%) patients in the sham OMT group had the primary outcome data available at 3 months. The mean (SD) Quebec Back Pain Disability Index scores for the standard OMT group were 31.5 (14.1) at baseline and 25.3 (15.3) at 3 months, and in the sham OMT group were 27.2 (14.8) at baseline and 26.1 (15.1) at 3 months. The mean reduction in LBP-specific activity limitations at 3 months was -4.7 (95% CI, -6.6 to -2.8) and -1.3 (95% CI, -3.3 to 0.6) for the standard OMT and sham OMT groups, respectively (mean difference, -3.4; 95% CI, -6.0 to -0.7; P = .01). At 12 months, the mean difference in mean reduction in LBP-specific activity limitations was -4.3 (95% CI, -7.6 to -1.0; P = .01), and at 3 and 12 months, the mean difference in mean reduction in pain was -1.0 (95% CI, -5.5 to 3.5; P = .66) and -2.0 (95% CI, -7.2 to 3.3; P = .47), respectively. There were no statistically significant differences in other secondary outcomes. Four and 8 serious adverse events were self-reported in the standard OMT and sham OMT groups, respectively, though none was considered related to OMT.In this randomized clinical trial of patients with nonspecific subacute or chronic LBP, standard OMT had a small effect on LBP-specific activity limitations vs sham OMT. However, the clinical relevance of this effect is questionable.ClinicalTrials.gov Identifier: NCT02034864.

Freed B., Williams B., Situ X., Landsman V., Kim J., Moroz A., Bang H., Park J.J.

Background: Blinding aims to minimize biases from what participants and investigators know or believe. Randomized controlled trials, despite being the gold standard to evaluate treatment effect, do not generally assess the success of blinding. We investigated the extent of blinding in back pain trials and the associations between participant guesses and treatment effects. Methods: We did a review with PubMed/OvidMedline, 2000–2019. Eligibility criteria were back pain trials with data available on treatment effect and participants’ guess of treatment. For blinding, blinding index was used as chance-corrected measure of excessive correct guess (0 for random guess). For treatment effects, within- or between-arm effect sizes were used. Analyses of investigators’ guess/blinding or by treatment modality were performed exploratorily. Results: Forty trials (3899 participants) were included. Active and sham treatment groups had mean blinding index of 0.26 (95% confidence interval: 0.12, 0.41) and 0.01 (−0.11, 0.14), respectively, meaning 26% of participants in active treatment believed they received active treatment, whereas only 1% in sham believed they received sham treatment, beyond chance, that is, random guess. A greater belief of receiving active treatment was associated with a larger within-arm effect size in both arms, and ideal blinding (namely, “random guess,” and “wishful thinking” that signifies both groups believing they received active treatment) showed smaller effect sizes, with correlation of effect size and summary blinding indexes of 0.35 ( p = 0.028) for between-arm comparison. We observed uniformly large sham treatment effects for all modalities, and larger correlation for investigator’s (un)blinding, 0.53 ( p = 0.046). Conclusion: Participants in active treatments in back pain trials guessed treatment identity more correctly, while those in sham treatments tended to display successful blinding. Excessive correct guesses (that could reflect weaker blinding and/or noticeable effects) by participants and investigators demonstrated larger effect sizes. Blinding and sham treatment effects on back pain need due consideration in individual trials and meta-analyses.

Cashin A.G., Lee H., Bagg M.K., O'Hagan E., Traeger A.C., Kamper S.J., Folly T., Jones M.D., Booth J., McAuley J.H.

Objectives The objective of this study was to review and assess the methodological quality of randomized controlled trials that test physical therapy interventions for low back pain. Study Design and Setting This is a 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 methodological quality. Results This review identified 2,215 trials. The majority of trials were for adults (n = 2136, 96.4%), low back pain without specific etiology (n = 1,863, 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%), and blinded assessors (n = 810, 36.6%), participants (n = 174, 7.9%), and therapists (n = 39, 1.8%). These findings did not vary by the type of therapy. Conclusion Most trials that test physical therapy interventions for low back pain have methodological limitations that could bias treatment effect estimates. Greater attention to 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.

Braithwaite F.A., Walters J.L., Moseley G.L., Williams M.T., McEvoy M.P.

Background/Aims: In clinical trials of physical interventions, participant blinding is often poorly addressed and therapist blinding routinely omitted. This situation presents a substantial barrier to moving the field forward. Improving the success of blinding will be a vital step towards determining the true mechanisms of physical interventions. We used a Delphi approach to identify important elements of shams for physical interventions to maximise the likelihood of participant and therapist blinding in clinical trials. Methods: Two expert groups were recruited: (1) experts in research methodology and (2) experts in deceptive and/or hypnotic techniques including magic. Magicians were included because they were considered a potentially rich source of innovation for developing credible shams due to their unique skills in altering perceptions and beliefs. Three rounds of survey were conducted, commencing with an open-ended question. Responses were converted to single ‘items’, which participants rated in the following two rounds using a 9-point Likert scale, categorised as ‘Not important’ (0–3), ‘Depends’ (4–6) and ‘Essential’ (7–9). Consensus was pre-defined as ≥80% agreement within a 3-point category. Results: Thirty-eight experts agreed to participate (research methodology: n = 22; deceptive and/or hypnotic techniques: n = 16), and 30 experts responded to at least one round (research methodology: n = 19; deceptive and/or hypnotic techniques: n = 11). Of 79 items, five reached consensus in the ‘Essential’ category in both groups, which related to beliefs of participants ( n = 3 items), interactions with researchers ( n = 1 item) and standardisation of clinical assessments ( n = 1 item). Thirteen additional items reached consensus in the ‘Essential’ category in one group. Experts in research methodology had one additional item reach consensus, related to authentic delivery of study information. The remaining 12 additional items that reached consensus in the deceptive and/or hypnotic techniques group related mainly to therapist attitude and behaviour and the clinical interaction. Conclusion: Experts agreed that, for shams to be believable, consideration of cognitive influences is essential. Contrary to the focus of previous shams for physical interventions, replicating the tactile sensation of the active treatment was not considered an essential part of sham development. Therefore, when designing sham-controlled clinical trials, researchers should carefully consider the cognitive credibility of the entire intervention experience, and not just the indistinguishability of the sham intervention itself. The findings provide new guidance to researchers on important contributors to blinding in physical intervention trials.

Beard D.J., Campbell M.K., Blazeby J.M., Carr A.J., Weijer C., Cuthbertson B.H., Buchbinder R., Pinkney T., Bishop F.L., Pugh J., Cousins S., Harris I.A., Lohmander L.S., Blencowe N., Gillies K., et. al.

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.

Rubinstein S.M., de Zoete A., van Middelkoop M., Assendelft W.J., de Boer M.R., van Tulder M.W.

Abstract Objective To assess the benefits and harms of spinal manipulative therapy (SMT) for the treatment of chronic low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, Physiotherapy Evidence Database (PEDro), Index to Chiropractic Literature, and trial registries up to 4 May 2018, including reference lists of eligible trials and related reviews. Eligibility criteria for selecting studies Randomised controlled trials examining the effect of spinal manipulation or mobilisation in adults (≥18 years) with chronic low back pain with or without referred pain. Studies that exclusively examined sciatica were excluded, as was grey literature. No restrictions were applied to language or setting. Review methods Two reviewers independently selected studies, extracted data, and assessed risk of bias and quality of the evidence. The effect of SMT was compared with recommended therapies, non-recommended therapies, sham (placebo) SMT, and SMT as an adjuvant therapy. Main outcomes were pain and back specific functional status, examined as mean differences and standardised mean differences (SMD), respectively. Outcomes were examined at 1, 6, and 12 months. Quality of evidence was assessed using GRADE. A random effects model was used and statistical heterogeneity explored. Results 47 randomised controlled trials including a total of 9211 participants were identified, who were on average middle aged (35-60 years). Most trials compared SMT with recommended therapies. Moderate quality evidence suggested that SMT has similar effects to other recommended therapies for short term pain relief (mean difference −3.17, 95% confidence interval −7.85 to 1.51) and a small, clinically better improvement in function (SMD −0.25, 95% confidence interval −0.41 to −0.09). High quality evidence suggested that compared with non-recommended therapies SMT results in small, not clinically better effects for short term pain relief (mean difference −7.48, −11.50 to −3.47) and small to moderate clinically better improvement in function (SMD −0.41, −0.67 to −0.15). In general, these results were similar for the intermediate and long term outcomes as were the effects of SMT as an adjuvant therapy. Evidence for sham SMT was low to very low quality; therefore these effects should be considered uncertain. Statistical heterogeneity could not be explained. About half of the studies examined adverse and serious adverse events, but in most of these it was unclear how and whether these events were registered systematically. Most of the observed adverse events were musculoskeletal related, transient in nature, and of mild to moderate severity. One study with a low risk of selection bias and powered to examine risk (n=183) found no increased risk of an adverse event (relative risk 1.24, 95% confidence interval 0.85 to 1.81) or duration of the event (1.13, 0.59 to 2.18) compared with sham SMT. In one study, the Data Safety Monitoring Board judged one serious adverse event to be possibly related to SMT. Conclusion SMT produces similar effects to recommended therapies for chronic low back pain, whereas SMT seems to be better than non-recommended interventions for improvement in function in the short term. Clinicians should inform their patients of the potential risks of adverse events associated with SMT.

Landsman V., Fillery M., Vernon H., Bang H.