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Responder analyses in randomised controlled trials for chronic low back pain: an overview of currently used methods.

ABSTRACT: To provide an overview and a critical appraisal of the use of responder analyses in published randomised controlled trials (RCTs) of interventions for chronic low back pain (LBP). The methodology used for the analyses, including the justification, as well as the implications of responder analyses on the conclusions was explored.A convenience sample of four systematic reviews evaluating 162 RCTs of interventions for chronic LBP was used to identify individual trials. Randomised trials were screened by two reviewers and included if they performed and reported a responder analysis (i.e. the proportion of participants achieving a pre-defined level of improvement). The cutoff value for responders, the period of follow-up, and the outcome measure used were extracted. Information on how RCT authors justified the methodology of their responder analyses was also appraised.Twenty-eight articles (17%) using 20 different definitions of responders were included in this appraisal. Justification for the definition of responders was absent in 80% of the articles. Pain was the most frequently used domain for the definition of response (50%), followed by back-specific function (30%) and a combination of pain and function (20%). A reduction in pain intensity ?50% was the most common threshold used to define responders (IQR 33-60%).Few RCTs of interventions for chronic LBP report responder analyses. Where responder analyses are used, the methods are inconsistent. When performing responder analyses authors are encouraged to follow the recommended guidelines, using empirically derived cutoffs, and present results alongside mean differences.

SUBMITTER: Henschke N

PROVIDER: S-EPMC3960418 | biostudies-other | 2014 Apr

REPOSITORIES: biostudies-other

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Responder analyses in randomised controlled trials for chronic low back pain: an overview of currently used methods.

Henschke Nicholas N van Enst Annefloor A Froud Robert R Ostelo Raymond W G RW

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 20140114 4

<h4>Purpose</h4>To provide an overview and a critical appraisal of the use of responder analyses in published randomised controlled trials (RCTs) of interventions for chronic low back pain (LBP). The methodology used for the analyses, including the justification, as well as the implications of responder analyses on the conclusions was explored.<h4>Methods</h4>A convenience sample of four systematic reviews evaluating 162 RCTs of interventions for chronic LBP was used to identify individual trial ...[more]

PMID: 24419902

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Project description:BACKGROUND:Low back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP. METHODS:A systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category. RESULTS:We included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds (n =?8, 5%), while low back pain (n =?150, 89%) with or without referred leg pain (n =?27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery (n =?84, 50%), pregnancy (n =?81, 48%), malignancy (n =?78, 46%), trauma (n =?63, 37%) and psychological conditions (n =?58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise (n =?44, 26%), neurological signs (n =?34, 20%) or disc herniation (n =?30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis (n =?35, 21%), spinal stenosis (n =?31, 18%) or osteoporosis (n =?27, 16%). CONCLUSION:RCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

Project description:ObjectiveMeta-analyses of analgesic medicines for low back pain often rescale measures of pain intensity to use mean difference (MD) instead of standardised mean difference for pooled estimates. Although this improves clinical interpretability, it is not clear whether this method is justified. Our study evaluated the justification for this method.MethodsWe identified randomised clinical trials of analgesic medicines for adults with low back pain that used two scales with different ranges to measure the same construct of pain intensity. We transformed all data to a 0-100 scale, then compared between-group estimates across pairs of scales with different ranges.ResultsTwelve trials were included. Overall, differences in means between pain intensity measures that were rescaled to a common 0-100 scale appeared to be small and randomly distributed. For one study that measured pain intensity on a 0-100 scale and a 0-10 scale; when rescaled to 0-100, the difference in MD between the scales was 0.8 points out of 100. For three studies that measured pain intensity on a 0-10 scale and 0-3 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.2 points out of 100 (range 5.5 points lower to 2.7 points higher). For two studies that measured pain intensity on a 0-100 scale and a 0-3 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.7 points out of 100 (range 6.2 points lower to 12.1 points higher). Finally, for six studies that measured pain intensity on a 0-100 scale and a 0-4 scale; when rescaled to 0-100, the average difference in MD between the scales was 0.7 points (range 5.4 points lower to 8.3 points higher).ConclusionRescaling pain intensity measures may be justified in meta-analyses of analgesic medicines for low back pain. Systematic reviewers may consider this method to improve clinical interpretability and enable more data to be included.Study registration/data availabilityOpen Science Framework (osf.io/8rq7f).

Project description:INTRODUCTION:Duloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP. PATIENTS AND METHODS:This was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12-14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ?30% reduction in Brief Pain Inventory (BPI) average pain ("pain reduction") at 12-14 weeks. The proportion of patients with ?30% and ?50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (?15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (?2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS:Compared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ?30% (59.7% vs 47.8%; P < 0.001) and ?50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ?30% (RR [95% CI], 2.91 [2.30-3.67]) or ?50% (3.24 [2.44-4.31]) pain reduction. Women were slightly more likely than men to achieve ?30% (RR [95% CI], 1.14 [1.00-1.30]) or ?50% (1.17 [0.99-1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ?2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ?30% reduction, ?2 painful sites 1.40 [1.18-1.66], isolated CLBP 1.07 [0.78-1.48]; ?50% reduction, ?2 painful sites 1.51 [1.20-1.89], isolated CLBP 1.23 [0.81-1.88]). CONCLUSION:Early pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.

Project description:BACKGROUND: There is considerable clinician and researcher interest in whether the outcomes for patients with low back pain, and the efficiency of the health systems that treat them, can be improved by 'subgrouping research'. Subgrouping research seeks to identify subgroups of people who have clinically important distinctions in their treatment needs or prognoses. Due to a proliferation of research methods and variability in how subgrouping results are interpreted, it is timely to open discussion regarding a conceptual framework for the research designs and statistical methods available for subgrouping studies (a method framework). The aims of this debate article are: (1) to present a method framework to inform the design and evaluation of subgrouping research in low back pain, (2) to describe method options when investigating prognostic effects or subgroup treatment effects, and (3) to discuss the strengths and limitations of research methods suitable for the hypothesis-setting phase of subgroup studies. DISCUSSION: The proposed method framework proposes six phases for studies of subgroups: studies of assessment methods, hypothesis-setting studies, hypothesis-testing studies, narrow validation studies, broad validation studies, and impact analysis studies. This framework extends and relabels a classification system previously proposed by McGinn et al (2000) as suitable for studies of clinical prediction rules. This extended classification, and its descriptive terms, explicitly anchor research findings to the type of evidence each provides. The inclusive nature of the framework invites appropriate consideration of the results of diverse research designs. Method pathways are described for studies designed to test and quantify prognostic effects or subgroup treatment effects, and examples are discussed. The proposed method framework is presented as a roadmap for conversation amongst researchers and clinicians who plan, stage and perform subgrouping research. SUMMARY: This article proposes a research method framework for studies of subgroups in low back pain. Research designs and statistical methods appropriate for sequential phases in this research are discussed, with an emphasis on those suitable for hypothesis-setting studies of subgroups of people seeking care.

Project description:IntroductionAcute, non-low back-related musculoskeletal pain is common and associated with significant socioeconomic costs. No review has evaluated all interventional studies for acute musculoskeletal pain, which limits attempts to make inferences regarding the relative effectiveness of treatments.Methods and analysisWe will conduct a systematic review of all randomised controlled trials evaluating therapies for acute musculoskeletal pain (excluding low back pain). We will identify eligible, English-language, trials by a systematic search of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, Physiotherapy Evidence Database (PEDro) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to February 2018. Eligible trials will: (1) enrol patients presenting with acute, non-low back-related musculoskeletal pain (duration of pain ?4 weeks), and (2) randomise patients to alternative interventions or an intervention and a placebo/sham arm. Fractures will be considered ineligible, unless they are non-surgical and therapy is directed at pain relief. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. Disagreements will be resolved through discussion to achieve consensus. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence supporting treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effect meta-analysis to establish the effectiveness of therapeutic interventions on patient-important outcomes; and (2) multiple treatment comparison meta-analysis to assess the relative effects of treatments. We will use a priori hypotheses to explain heterogeneity between studies. We will use STATA V.14.2 for all analyses.Ethics and disseminationNo research ethics approval is required for this systematic review, as no confidential patient data will be used. The results of this systematic review will be disseminated through publication in a peer-reviewed journal, conference presentations and will inform a clinical practice guideline.Prospero registration numberCRD42018094412.

Project description:BackgroundThere is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies.Methods and findingsSearches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93-1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance.ConclusionsEmpirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary.

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Responder analyses in randomised controlled trials for chronic low back pain: an overview of currently used methods.

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Responder analyses in randomised controlled trials for chronic low back pain: an overview of currently used methods.

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