Dataset Information

Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

ABSTRACT:

Objective

Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials.

Methods

We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain.

Results

There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant.

Conclusions

Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.

SUBMITTER: Dworkin RH

PROVIDER: S-EPMC3770199 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

Dworkin Robert H RH Turk Dennis C DC Peirce-Sandner Sarah S He Hua H McDermott Michael P MP Farrar John T JT Katz Nathaniel P NP Lin Allison H AH Rappaport Bob A BA Rowbotham Michael C MC

Neurology 20130522 1

<h4>Objective</h4>Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials.<h4>Methods</h4>We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain.<h4>Results</h4>There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regre ...[more]

PMID: 23700332

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Project description:IntroductionChronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all interventional studies for chronic neuropathic 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 chronic neuropathic pain. We will identify eligible trials, in any language, by a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, DARE, PsychINFO and the Cochrane Central Registry of Controlled Trials. Eligible trials will be: (1) enrol patients presenting with chronic neuropathic pain, and (2) randomise patients to alternative interventions (pharmacological or non-pharmacological) or an intervention and a control arm. 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 of eligible studies, recommendations from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes we will collect, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate our confidence in treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effects meta-analysis to establish the effect of reported therapies on patient-important outcomes; and (2) a multiple treatment comparison meta-analysis within a Bayesian framework to assess the relative effects of treatments. We will define a priori hypotheses to explain heterogeneity between studies, and conduct meta-regression and subgroup analyses consistent with the current best practices.Ethics and disseminationWe do not require ethics approval for our proposed review. We will disseminate our findings through peer-reviewed publications and conference presentations.Trial registration numberPROSPERO (CRD42014009212).

Project description:OBJECTIVE:To assess the benefits and harms of pregabalin in the management of neuropathic pain. DESIGN:Rapid review and meta-analysis of phase III, randomised, placebo-controlled trials. PARTICIPANTS:Adults aged 18 years and above with neuropathic pain defined according to the International Association for the Study of Pain criteria. INTERVENTIONS:Pregabalin or placebo. PRIMARY AND SECONDARY OUTCOME MEASURES:Our primary outcomes were pain (as measured using validated scales) and adverse events. Our secondary outcomes were sleep disturbance, quality of life, Patient Global Impression of Change, Clinician Global Impression scale, anxiety and depression scores, overall discontinuations and discontinuations because of adverse events. RESULTS:We included 28 trials comprising 6087 participants. The neuropathic pain conditions studied were diabetic peripheral neuropathy, postherpetic neuralgia, herpes zoster, sciatica (radicular pain), poststroke pain and spinal cord injury-related pain. Patients who took pregabalin reported significant reductions in pain (numerical rating scale (NRS)) compared with placebo (standardised mean difference (SMD) -0.49 (95% CI -0.66 to -0.32, p<0.00001), very low quality evidence). Pregabalin significantly reduced sleep interference scores (NRS) compared with placebo (SMD -0.38 (95% CI -0.50 to -0.26, p<0.00001), moderate quality evidence. Pregabalin significantly increased the risk of adverse events compared with placebo (RR 1.33 (95% CI 1.23 to 1.44, p<0.00001, low quality evidence)). The risks of experiencing weight gain, somnolence, dizziness, peripheral oedema, fatigue, visual disturbances, ataxia, non-peripheral oedema, vertigo and euphoria were significantly increased with pregabalin. Pregabalin was significantly more likely than placebo to lead to discontinuation of the drug because of adverse events (RR 1.91 (95% CI 1.54 to 2.37, p<0.00001), low quality evidence). CONCLUSION:Pregabalin has beneficial effects on some symptoms of neuropathic pain. However, its use significantly increases the risk of a number of adverse events and discontinuation due to adverse events. The quality of the evidence from journal publications is low.

Project description:BackgroundCentral neuropathic pain (CNP) is an excruciating condition, prevalent in up to a third of patients with multiple sclerosis (MS). Identifying CNP among MS patients is particularly challenging considering the ample comorbid chronic pain conditions and sensory disturbances entailed by the disease. The aim was to identify sensory features unique to CNP beyond those of chronic pain and MS.MethodsParticipants were 112 MS patients: 44 with a diagnosis of CNP, 28 with a diagnosis of chronic musculoskeletal pain (MSP), and 40 pain free. Participants underwent testing of thermal and mechanical thresholds, thermal grill illusion (TGI), pain adaptation (PA), and offset analgesia (OA), and chronic pain was characterized. A two-step cluster analysis was performed, and the association between the cluster membership and the clinical group membership (CNP, MSP, pain free) was evaluated.ResultsThe CNP and MSP groups were similar in most of the chronic pain variables (e.g., severity, location and quality) and MS-related variables (e.g., type, severity and medication intake). The three created clusters had unique sensory features: (1) 'Hyposensitivity' (increased thermal and touch thresholds) characterized the CNP group; (2) 'Poor inhibition and hyperalgesia' (worst PA and OA and decreased TGI threshold) characterized the MSP group; and (3) 'Efficient inhibition' (best PA and OA, smallest sensory loss) characterized the pain-free group.ConclusionsThe unique sensory features of CNP and MSP provide insight into their pathophysiology, and evaluating them may increase the ability to provide individually based interventions. Efficient inhibition may protect MS patients from chronic pain.SignificanceCluster analysis among patients with multiple sclerosis (MS) revealed that while central neuropathic pain is associated with thermal and mechanical hypoesthesia, musculoskeletal pain is involved with reduced pain inhibition and hyperalgesia; sensory profiles that provide insights into the mechanisms of these conditions and may promote an individually based pain management.

Dataset Information

Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

Objective

Methods

Results

Conclusions

Publications

Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

Similar Datasets

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