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A threshold analysis assessed the credibility of conclusions from network meta-analysis.

ABSTRACT: OBJECTIVE:To assess the reliability of treatment recommendations based on network meta-analysis (NMA). STUDY DESIGN AND SETTING:We consider evidence in an NMA to be potentially biased. Taking each pairwise contrast in turn, we use a structured series of threshold analyses to ask: (1) "How large would the bias in this evidence base have to be before it changed our decision?" and (2) "If the decision changed, what is the new recommendation?" We illustrate the method via two NMAs in which a Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment for NMAs has been implemented: weight loss and osteoporosis. RESULTS:Four of the weight-loss NMA estimates were assessed as "low" and six as "moderate" quality by GRADE; for osteoporosis, six were "low," nine were "moderate," and 1 was "high." The threshold analysis suggests plausible bias in 3 of 10 estimates in the weight-loss network could have changed the treatment recommendation. For osteoporosis, plausible bias in 6 of 16 estimates could change the recommendation. There was no relation between plausible bias changing a treatment recommendation and the original GRADE assessments. CONCLUSIONS:Reliability judgments on individual NMA contrasts do not help decision makers understand whether a treatment recommendation is reliable. Threshold analysis reveals whether the final recommendation is robust against plausible degrees of bias in the data.

SUBMITTER: Caldwell DM

PROVIDER: S-EPMC5176010 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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A threshold analysis assessed the credibility of conclusions from network meta-analysis.

Caldwell Deborah M DM Ades A E AE Dias Sofia S Watkins Sarah S Li Tianjing T Taske Nichole N Naidoo Bhash B Welton Nicky J NJ

Journal of clinical epidemiology 20160716

<h4>Objective</h4>To assess the reliability of treatment recommendations based on network meta-analysis (NMA).<h4>Study design and setting</h4>We consider evidence in an NMA to be potentially biased. Taking each pairwise contrast in turn, we use a structured series of threshold analyses to ask: (1) "How large would the bias in this evidence base have to be before it changed our decision?" and (2) "If the decision changed, what is the new recommendation?" We illustrate the method via two NMAs in ...[more]

PMID: 27430731

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Project description:BackgroundNegative margins are associated with reduced risk of ipsilateral breast tumor recurrence (IBTR) for women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). However, there is no consensus about the best minimum margin width.MethodsWe searched the PubMed database for studies of DCIS published in English between January 1970 and July 2010 and examined the relationship between IBTR and margin status after BCS for DCIS. Women with DCIS were stratified into two groups, BCS with or without radiotherapy. We used frequentist and Bayesian approaches to estimate the odds ratios (OR) of IBTR for groups with negative margins and positive margins. We further examined specific margin thresholds using mixed treatment comparisons and meta-regression techniques. All statistical tests were two-sided.ResultsWe identified 21 studies published in 24 articles. A total of 1066 IBTR events occurred in 7564 patients, including BCS alone (565 IBTR events in 3098 patients) and BCS with radiotherapy (501 IBTR events in 4466 patients). Compared with positive margins, negative margins were associated with reduced risk of IBTR in patients with radiotherapy (OR = 0.46, 95% credible interval [CrI] = 0.35 to 0.59), and in patients without radiotherapy (OR = 0.34, 95% CrI = 0.24 to 0.47). Compared with patients with positive margins, the risk of IBTR for patients with negative margins was smaller (negative margin >0 mm, OR = 0.45, 95% CrI = 0.38 to 0.53; >2 mm, OR = 0.38, 95% CrI = 0.28 to 0.51; >5 mm, OR = 0.55, 95% CrI = 0.15 to 1.30; and >10 mm, OR = 0.17, 95% CrI = 0.12 to 0.24). Compared with a negative margin greater than 2 mm, a negative margin of at least 10 mm was associated with a lower risk of IBTR (OR = 0.46, 95% CrI = 0.29 to 0.69). We found a probability of .96 that a negative margin threshold greater than 10 mm is the best option compared with other margin thresholds.ConclusionsNegative surgical margins should be obtained for DCIS patients after BCS regardless of radiotherapy. Within cosmetic constraint, surgeons should attempt to achieve negative margins as wide as possible in their first attempt. More studies are needed to understand whether margin thresholds greater than 10 mm are warranted.

Project description:BACKGROUND:Although there are many nonsurgical treatment options for the primary management of chronic ankle instability, the most effective nonoperative intervention has not been defined. QUESTIONS/PURPOSES:The purpose of this study was to perform a network meta-analysis to compare the results of different standalone and/or combined nonsurgical interventions on chronic ankle instability as measured by (1) the Cumberland Ankle Instability Tool (CAIT) at 0 to 6 months after treatment and (2) treatment-related complications. METHODS:We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus in August 2017 for completed studies published between 2005 and 2016. We conducted random-effects pairwise and network meta-analysis considering randomized trials, which compared the effects of various nonoperative therapies for ankle instability. Studies assessing patients with functional ankle instability and/or mechanical ankle instability and/or recurrent ankle sprains were eligible for inclusion. After combining data from self-administered questionnaires, we analyzed patient self-reported outcomes of function at the end of the rehabilitation period and 1 to 6 months after treatment. We thereafter reexpressed standardized mean differences to mean differences with CAIT. For this instrument, scores vary between 0 and 30, and higher scores indicate better ankle stability. We included 21 trials involving 789 chronically unstable ankles. The rehabilitation interventions included, but were not limited to, balance training, strengthening exercises, a combination of the balance and strengthening exercises, manual therapy, and multimodal treatment. The implemented multistation protocols were targeted at four main areas of rehabilitation (ROM, balance, strength, and overall activity). Control was defined as placebo and/or wait and see. Treatment-related complications were defined as any major or minor adverse event observed after rehabilitation as reported by the source studies. Statistically, we did not detect significant inconsistency in the network meta-analysis. We also assessed the quality of the trials using the Cochrane risk of bias tool and judged 12, eight, and one studies to be at a low, unclear, and high risk of bias, respectively. We also considered the quality of evidence to be of moderate strength utilizing the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We defined the minimum clinically important difference (MCID) in the CAIT to be 3 points. RESULTS:A 4-week supervised rehabilitation program, which included balance training, strengthening, functional tasks, and ROM exercises, was favored over control according to the results of four trials by a clinically important margin (mean difference between multimodal and control groups in the CAIT was -10; 95% confidence interval [CI], -16 to -3; p = 0.001). Among the standalone interventions, only balance training was better than control according to the findings of seven trials (mean difference between balance training and control in the CAIT was -5; 95% CI, -10 to -0.03; p = 0.049); this difference likewise exceeded the MCID and so is believed to be a clinically important difference. Adverse events associated with the enrolled rehabilitation protocols were transient, mild, and uncommon. CONCLUSIONS:Although a supervised impairment-based program after chronic ankle instability was superior to control, we note that followup in the included trials tended to be short and inconsistent, although the effect size exceeded the MCID and so likely would be identified as clinically important by patients. Future randomized trials should determine whether the short-term benefits of these interventions are sustained over time. LEVEL OF EVIDENCE:Level I, therapeutic study.

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A threshold analysis assessed the credibility of conclusions from network meta-analysis.

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A threshold analysis assessed the credibility of conclusions from network meta-analysis.

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