Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.

BACKGROUND: Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline. METHODS/DESIGN: The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses. ETHICS AND DISSEMINATION: Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

Exploring the pain and disability continuum in adolescents with non-traumatic anterior knee pain: a mediation analysis using individual participant data of prospective studies.

OBJECTIVE: To use individual patient data (IPD) to investigate if the effect of pain on sports-related disability is mediated through physical (lower extremity isometric strength) or psychological (depression/anxiety and knee confidence) factors in adolescents with non-traumatic anterior knee pain. METHODS: This study included four datasets from a previously harmonised IPD dataset. Prior to analysis, the protocol and analysis approach were predefined and published on Open Science Framework. Potential mediators were pre-sepcified as isometric knee and hip strengths, self-reported anxiety/depression and confidence in the knee, allmeasured at 12 weeks after baseline evaluation. Mediation analyses were undertaken using the CMAVerse package in RStudio using the regression-based approach to decompose the total effect of the exposure (pain at baseline evaluation) on the outcome (sports-related disability at 6 months) into the 'indirect effect' (the portion of the total effect acting through the mediators) and the 'direct effect'. RESULTS: Two-hundred and seventy-nine adolescents with non-traumatic knee pain were included in the analysis. Median age was 13 (range 10-19), and 72% were women. Baseline pain was associated with sports-related disability at 6 months. There was no evidence of the association being mediated by any of the proposed mediators (total natural indirect effect for strength 0.01 (-1.14 to 1.80) and psychological factors 0.00 (-0.66 to 2.02)). CONCLUSION: We found an effect of pain on sports-related disability at 6 months which appears to be independent of lower extremity muscle strength, or depression/anxiety and knee confidence in adolescents with non-traumatic anterior knee pain.

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.

Importance: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice. Objective: To assess the reporting of observational studies that explicitly aimed to emulate a target trial. Evidence Review: We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation. Findings: A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation. Conclusion and Relevance: In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

Mechanisms of education and graded sensorimotor retraining in people with chronic low back pain: a mediation analysis.

ABSTRACT: An improved understanding of the biopsychosocial influences that contribute to and maintain pain has promoted the development of new efficacious treatments for chronic low back pain (CLBP). This study aimed to investigate the mechanisms of a new treatment-education and graded sensorimotor retraining-on pain and disability. We conducted a preplanned causal mediation analysis of a randomized clinical trial which allocated 276 participants with CLBP to 12 weekly clinical sessions of education and graded sensorimotor retraining (n = 138) or a sham and attention control (n = 138). Outcomes were pain intensity and disability, both assessed at 18 weeks. Hypothesized mediators included tactile acuity, motor coordination, back self-perception, beliefs about the consequences of back pain, kinesiophobia, pain self-efficacy, and pain catastrophizing, all assessed at the end of treatment (12 weeks). Four of 7 mechanisms (57%) mediated the intervention effect on pain; the largest mediated effects were for beliefs about back pain consequences (-0.96 [-1.47 to -0.64]), pain catastrophizing (-0.49 [-0.61 to -0.24]), and pain self-efficacy (-0.37 [-0.66 to -0.22]). Five of 7 mechanisms (71%) mediated the intervention effect on disability; the largest mediated effects were for beliefs about back pain consequences (-1.66 [-2.62 to -0.87]), pain catastrophizing (-1.06 [-1.79 to -0.53]), and pain self-efficacy (-0.84 [-1.89 to -0.45]). When all 7 mechanisms were considered simultaneously, the joint mediation effect explained most of the intervention effect for both pain and disability. Optimizing interventions to target beliefs about the consequences of back pain, pain catastrophizing, and pain self-efficacy is likely to lead to improved outcomes for people with CLBP.

Pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews.

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.

Mechanisms of vocational interventions for return to work from musculoskeletal conditions: a mediation analysis of the MI-NAV trial.

OBJECTIVES: To investigate whether and to what extent, return to work (RTW) expectancy and workability mediate the effect of two vocational interventions on reducing sickness absence in workers on sick leave from a musculoskeletal condition. METHODS: This is a preplanned mediation analysis of a three-arm parallel randomised controlled trial which included 514 employed working adults with musculoskeletal conditions on sick leave for at least 50% of their contracted work hours for ≥7 weeks. Participants were randomly allocated (1:1:1) to one of three treatment arms; usual case management (UC) (n=174), UC plus motivational interviewing (MI) (n=170) and UC plus a stratified vocational advice intervention (SVAI) (n=170). The primary outcome was the number of sickness absence days over 6 months from randomisation. Hypothesised mediators included RTW expectancy and workability assessed 12 weeks after randomisation. RESULTS: The mediated effect of the MI arm compared with UC on sickness absence days through RTW expectancy was -4.98 days (-8.89 to -1.04), and workability was -3.17 days (-8.55 to 2.32). The mediated effect of the SVAI arm compared with UC on sickness absence days through RTW expectancy was -4.39 days (-7.60 to -1.47), and workability was -3.21 days (-7.90 to 1.50). The mediated effects for workability were not statistically significant. CONCLUSIONS: Our study provides new evidence for the mechanisms of vocational interventions to reduce sickness absence related to sick leave due to musculoskeletal conditions. Changing an individual's expectation that RTW is likely may result in meaningful reductions in sickness absence days. TRIAL REGISTRATION NUMBER: NCT03871712.

Mixed messages: most spinal pain and osteoarthritis observational research is unclear or misaligned.

OBJECTIVES: We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or osteoarthritis. STUDY DESIGN AND SETTING: We searched five databases for observational studies that included people with spinal pain or osteoarthritis published in the last 5 years. We randomized 100 eligible studies, and classified study intent (aims and methods) and interpretations as causal, non-causal, unclear, or misaligned. RESULTS: Overall, 38% of studies were aligned regarding their intent and interpretation (either causally (22%) or non-causally (16%)). 29% of studies' aims and 29% of study methods were unclear. Intent was misaligned in 16% of studies (where aim differed to method) and 23% of studies had misaligned interpretations (where there were multiple conflicting claims). The most common kind of aim was non-causal (38%), and the most common type of method (39%), intent (38%), and interpretations (35%) was causal. CONCLUSIONS: Misalignment and mixed messages are common in observational research of spinal pain and osteoarthritis. More than 6 in 10 observational studies may be uninterpretable, because study intent and interpretations do not align. While causal methods and intent are most common in observational research, authors commonly shroud causal intent in non-causal terminology.

The effect of face-to-face versus online learning on student performance in anatomy: an observational study using a causal inference approach.

Introduction: This study aimed to estimate the causal effect of face-to-face learning on student performance in anatomy, compared to online learning, by analysing examination marks under a causal structure. Methods: We specified a causal graph to indicate how the mode of learning affected student performance. We sampled purposively to obtain end-semester examination marks of undergraduate and postgraduate students who learned using face-to-face (pre-COVID, 2019) or online modes (post-COVID, 2020). The analysis was informed by the causal graph. Marks were compared using linear regression, and sensitivity analyses were conducted to assess if effects were robust to unmeasured confounding. Results: On average, face-to-face learning improved student performance in the end-semester examination in undergraduate students (gain of mean 8.3%, 95% CI 3.3 to 13.4%; E-value 2.77, lower limit of 95% CI 1.80) but lowered performance in postgraduate students (loss of 8.1%, 95% CI 3.6 to 12.6%; E-value 2.89, lower limit of 95% CI 1.88), compared to online learning. Discussion: Under the assumed causal graph, we found that compared to online learning, face-to-face learning improved student performance in the end-semester examination in undergraduate students, but worsened student performance in postgraduate students. These findings suggest that different modes of learning may suit different types of students. Importantly, this is the first attempt to estimate causal effects of the mode of learning on student performance under a causal structure. This approach makes our assumptions transparent, informs data analysis, and is recommended when using observational data to make causal inferences.

Estimating the effect of COVID-19 on trial design characteristics: a registered report.

There have been reports of poor-quality research during the COVID-19 pandemic. This registered report assessed design characteristics of registered clinical trials for COVID-19 compared to non-COVID-19 trials to empirically explore the design of clinical research during a pandemic and how it compares to research conducted in non-pandemic times. We did a retrospective cohort study with a 1 : 1 ratio of interventional COVID-19 registrations to non-COVID-19 registrations, with four trial design outcomes: use of control arm, randomization, blinding and prospective registration. Logistic regression was used to estimate the odds ratio of investigating COVID-19 versus not COVID-19 and estimate direct and total effects of investigating COVID-19 for each outcome. The primary analysis showed a positive direct and total effect of COVID-19 on the use of control arms and randomization. It showed a negative direct effect of COVID-19 on blinding but no evidence of a total effect. There was no evidence of an effect on prospective registration. Taken together with secondary and sensitivity analyses, our findings are inconclusive but point towards a higher prevalence of key design characteristics in COVID-19 trials versus controls. The findings do not support much existing COVID-19 research quality literature, which generally suggests that COVID-19 led to a reduction in quality. Limitations included some data quality issues, minor deviations from the pre-registered plan and the fact that trial registrations were analysed which may not accurately reflect study design and conduct. Following in-principle acceptance, the approved stage 1 version of this manuscript was pre-registered on the Open Science Framework at https://doi.org/10.17605/OSF.IO/5YAEB. This pre-registration was performed prior to data analysis.

Registration of health and medical research.

Registration of health and medical research is an effective way of improving the transparency and credibility of evidence. Registration involves pre-specifying the research objectives, design, methods and analytic plan on a publicly accessible repository before conducting the study. Registration can reduce bias and improve the transparency and credibility of research findings. Registration is mandated for clinical trials, but it is also relevant to systematic reviews, observational and preclinical experimental research. This paper describes how researchers can register their research and outlines possible barriers and challenges in doing so. Widespread adoption of research registration can reduce research waste and improve evidence-informed clinical and policy decision making.

How Do Nonsurgical Interventions Improve Pain and Physical Function in People With Osteoarthritis? A Scoping Review of Mediation Analysis Studies.

OBJECTIVE: Nonsurgical interventions are recommended for osteoarthritis (OA). However, how interventions change pain and physical function is unclear. Therefore, the objectives of this scoping review were to 1) identify what potential mediators of nonsurgical interventions on pain and physical function have been evaluated and 2) summarize the findings according to intervention, joint, and outcome. METHODS: We searched Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Scopus databases. Studies were included if they conducted a mediation analysis on a randomized controlled trial evaluating a nonsurgical intervention on OA of any joint. Outcomes were pain and physical function. RESULTS: Nine knee OA studies, evaluating diet plus exercise, exercise, unloading shoes, high-expectation communication during acupuncture, and telephone-based weight loss plus exercise were identified. Except for weight loss and self-efficacy, putative mediators (knee muscle perfusion/extensor strength/adduction moment, systemic inflammatory biomarkers, physical activity, dietary intake, and pain beliefs) were evaluated by single studies. Ten mediators partially mediated intervention (diet plus exercise, exercise, high-expectation communication) effects on pain and physical function. Eight mediators were common to pain and function (reduced weight, increased knee extensor strength, and increased self-efficacy). Constant knee flexor muscle perfusion partially mediated exercise effects on pain, and knee pain relief partially mediated exercise effects on function. CONCLUSION: In knee OA, some evidence suggests that the benefits of 1) diet and exercise are mediated through changes in body weight, systemic inflammation, and self-efficacy; 2) exercise is mediated through changes in knee muscle strength and self-efficacy; and 3) high-expectation communication style is mediated through changes in self-efficacy.

Sharing study materials in health and medical research.

Making study materials available allows for a more comprehensive understanding of the scientific literature. Sharing can take many forms and include a wide variety of outputs including code and data. Biomedical research can benefit from increased transparency but faces unique challenges for sharing, for instance, confidentiality concerns around participants' medical data. Both general and specialised repositories exist to aid in sharing most study materials. Sharing may also require skills and resources to ensure that it is done safely and effectively. Educating researchers on how to best share their materials, and properly rewarding these practices, requires action from a variety of stakeholders including journals, funders and research institutions.

Open science and conflict of interest policies of medical and health sciences journals before and during the COVID-19 pandemic: A repeat cross-sectional study: Open science policies of medical journals.

Objectives: To audit the transparent and open science standards of health and medical sciences journal policies and explore the impact of the COVID-19 pandemic. Design: Repeat cross-sectional study. Setting: 19 journals listed in Google Scholar's Top Publications for health and medical sciences. Participants: Blood, Cell, Circulation, European Heart Journal, Gastroenterology, Journal of Clinical Oncology, Journal of the American College of Cardiology, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, PLoS ONE, Proceedings of the National Academy of Sciences, Science Translational Medicine, The British Medical Journal, The Journal of the American Medical Association, The Lancet, The Lancet Oncology, and The New England Journal of Medicine. Main outcome measures: We used the Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) to evaluate journals standards. Results: TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021, but overall, scores were very low at both time points. Journal policies scored highest for their adherence to data transparency and scored lowest for preregistration of study protocols and analysis plans and the submission of replication studies. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n = 16) and during (95%; n = 18) the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has highlighted the importance of practising open science. However, requirements for open science practices in audited policies were overall low, which may impede progress in health and medical research. As key stakeholders in disseminating research, journals should promote a research culture of greater transparency and more robust open science practices.

Feasibility of an Audit and Feedback Intervention to Facilitate Journal Policy Change Towards Greater Promotion of Transparency and Openness in Sports Science Research.

OBJECTIVES: To evaluate (1) the feasibility of an audit-feedback intervention to facilitate sports science journal policy change, (2) the reliability of the Transparency of Research Underpinning Social Intervention Tiers (TRUST) policy evaluation form, and (3) the extent to which policies of sports science journals support transparent and open research practices. METHODS: We conducted a cross-sectional, audit-feedback, feasibility study of transparency and openness standards of the top 38 sports science journals by impact factor. The TRUST form was used to evaluate journal policies support for transparent and open research practices. Feedback was provided to journal editors in the format of a tailored letter. Inter-rater reliability and agreement of the TRUST form was assessed using intraclass correlation coefficients and the standard error of measurement, respectively. Time-based criteria, fidelity of intervention delivery and qualitative feedback were used to determine feasibility. RESULTS: The audit-feedback intervention was feasible based on the time taken to rate journals and provide tailored feedback. The mean (SD) score on the TRUST form (range 0-27) was 2.05 (1.99), reflecting low engagement with transparent and open practices. Inter-rater reliability of the overall score of the TRUST form was moderate [ICC (2,1) = 0.68 (95% CI 0.55-0.79)], with standard error of measurement of 1.17. However, some individual items had poor reliability. CONCLUSION: Policies of the top 38 sports science journals have potential for improved support for transparent and open research practices. The feasible audit-feedback intervention developed here warrants large-scale evaluation as a means to facilitate change in journal policies. REGISTRATION: OSF ( https://osf.io/d2t4s/ ).

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

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.

"Myths and Facts" Education Is Comparable to "Facts Only" for Recall of Back Pain Information but May Improve Fear-Avoidance Beliefs: An Embedded Randomized Trial.

OBJECTIVE: To assess the effectiveness of patient education with "myths and facts" versus "facts only" on recall of back pain information and fear-avoidance beliefs in patients with chronic low back pain (LBP). DESIGN: Randomized Study Within A Trial. METHODS: One hundred fifty-two participants with chronic LBP were included. Participants allocated to the "facts only" group received an information sheet with 6 LBP facts, whereas those allocated to the "myths and facts" group received the same information sheet, with each myth refuted by its respective fact. The primary outcome was a correct recall of back pain facts, and the secondary outcome was the physical activity component of the Fear-Avoidance Beliefs Questionnaire (FABQ-PA), 2 weeks after the provision of the information sheet. RESULTS: There was no evidence of a difference in the proportion of participants with a correct recall between the "myths and facts" and "facts only" groups (odds ratio = 0.98; 95% confidence interval [CI]: 0.48, 1.99) and no significant difference in FABQ-PA mean scores between groups (-1.58; 95% CI: -3.77, 0.61). Sensitivity analyses adjusted for prognostic factors showed no difference in information recall but a larger difference in FABQ-PA scores (-2.3; 95% CI: -4.56, -0.04). CONCLUSION: We found no overall difference in the recall of back pain information for patients provided with "myths and facts" compared with that for patients provided with "facts only" and a slight reduction in fear-avoidance beliefs for physical activity using "myths and facts" compared with that using "facts only," but the meaningfulness of this result is uncertain. J Orthop Sports Phys Ther 2022;52(9):586-594. Epub: 9 July 2022. doi:10.2519/jospt.2022.10989.

What Are the Mechanisms of Action of Cognitive-Behavioral, Mind-Body, and Exercise-based Interventions for Pain and Disability in People With Chronic Primary Musculoskeletal Pain?: A Systematic Review of Mediation Studies From Randomized Controlled Trials.

OBJECTIVES: This systematic review examined studies that used mediation analysis to investigate the mechanisms of action of cognitive-behavioral, mind-body, and exercise-based interventions for pain and disability in people with chronic primary musculoskeletal pain. MATERIALS AND METHODS: We searched 5 electronic databases for articles that conducted mediation analyses of randomized controlled trials to either test or estimate indirect effects. RESULTS: We found 17 studies (n=4423), including 90 mediation models examining the role of 22 putative mediators on pain or disability, of which 4 had partially mediated treatment effect; 8 had mixed results, and 10 did not mediate treatment effect. The conditions studied were chronic whiplash-associated pain, chronic low back pain, chronic knee pain, and mixed group of chronic primary musculoskeletal pain. DISCUSSION: We observed that several of the studies included in our systematic review identified similar mechanisms of action, even between different interventions and conditions. However, methodological limitations were common. In conclusion, there are still substantial gaps with respect to understanding how cognitive-behavioral, mind-body, and exercise-based interventions work to reduce pain and disability in people with chronic primary musculoskeletal pain.

A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols.

OBJECTIVES: Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency. STUDY DESIGN AND SETTING: In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results. We determined the proportion of RCTs with (1) publicly available protocols, (2) publications citing the protocol, and (3) registries providing a link to the protocol. A multivariable logistic regression model explored factors associated with protocol availability. RESULTS: Three hundred twenty-six RCTs were included, of which 118 (36.2%) made their protocol publicly available; 56 (47.6% 56 of 118) provided as a peer-reviewed publication and 48 (40.7%, 48 of 118) provided as supplementary material. A total of 90.9% (100 of 110) of the protocols were cited in the main publication, and 55.9% (66 of 118) were linked in the clinical trial registry. Larger sample size (>500; odds ratio [OR] = 5.90, 95% confidence interval [CI], 2.75-13.31) and investigator sponsorship (OR = 1.99, 95% CI, 1.11-3.59) were associated with increased protocol availability. Most protocols were made available shortly before the publication of the main results. CONCLUSION: RCT protocols should be made available at an early stage of the trial.