Sharing information across patient subgroups to draw conclusions from sparse treatment networks.

Network meta-analysis (NMA) usually provides estimates of the relative effects with the highest possible precision. However, sparse networks with few available studies and limited direct evidence can arise, threatening the robustness and reliability of NMA estimates. In these cases, the limited amount of available information can hamper the formal evaluation of the underlying NMA assumptions of transitivity and consistency. In addition, NMA estimates from sparse networks are expected to be imprecise and possibly biased as they rely on large-sample approximations that are invalid in the absence of sufficient data. We propose a Bayesian framework that allows sharing of information between two networks that pertain to different population subgroups. Specifically, we use the results from a subgroup with a lot of direct evidence (a dense network) to construct informative priors for the relative effects in the target subgroup (a sparse network). This is a two-stage approach where at the first stage, we extrapolate the results of the dense network to those expected from the sparse network. This takes place by using a modified hierarchical NMA model where we add a location parameter that shifts the distribution of the relative effects to make them applicable to the target population. At the second stage, these extrapolated results are used as prior information for the sparse network. We illustrate our approach through a motivating example of psychiatric patients. Our approach results in more precise and robust estimates of the relative effects and can adequately inform clinical practice in presence of sparse networks.

Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis.

BACKGROUND: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA). METHODS: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months. RESULTS: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed. CONCLUSIONS: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42020169494 .

Comparing Efficacy and Safety in Catheter Ablation Strategies for Paroxysmal Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

Although catheter ablation (CA) is an established treatment for paroxysmal atrial fibrillation (PAF), there is no consensus regarding the most efficient CA strategy. The objective of this network meta-analysis (NMA) was to compare the efficacy and safety of different CA strategies for PAF. A systematic search was performed in PubMed, Web of Science, and CENTRAL until the final search date, 5 October 2020. Randomised controlled trials (RCT) comparing different CA strategies and methods for pulmonary vein isolation (PVI) were included. Efficacy was defined as lack of arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of six months. In total, 43 RCTs comparing 11 different CA strategies involving 6701 patients were included. The risk of recurrence was significantly decreased in comparison with PVI with radiofrequency only for the following treatments: PVI with adjuvant ablation (RR: 0.79, CI: 0.65-0.97) and PVI with sympathetic modulation (RR: 0.64, CI: 0.46-0.88). However, PVI with radiofrequency was superior to non-PVI strategies (RR: 1.65, CI: 1.2-2.26). No statistically significant difference was found in safety between different CA strategies. Concerning different PVI strategies, no difference was observed either in efficacy or in safety between tested strategies. This NMA suggests that different PVI strategies are generally similar in terms of efficacy, while PVI with additional ablation or sympathetic modulation may be more effective than PVI alone. This study provides decision-makers with insights into the efficacy and safety of different CA strategies.

Challenges in meta-analyses with observational studies.

OBJECTIVE: Meta-analyses of observational studies are frequently published in the literature, but they are generally considered suboptimal to those involving randomised controlled trials (RCTs) only. This is due to the increased risk of biases that observational studies may entail as well as because of the high heterogeneity that might be present. In this article, we highlight aspects of meta-analyses with observational studies that need more careful consideration in comparison to meta-analyses of RCTs. METHODS: We present an overview of recommendations from the literature with respect to how the different steps of a meta-analysis involving observational studies should be comprehensively conducted. We focus more on issues arising at the step of the quantitative synthesis, in terms of handling heterogeneity and biases. We briefly describe some sophisticated synthesis methods, which may allow for more flexible modelling approaches than common meta-analysis models. We illustrate the issues encountered in the presence of observational studies using an example from mental health, which assesses the risk of myocardial infarction in antipsychotic drug users. RESULTS: The increased heterogeneity observed among studies challenges the interpretation of the diamond, while the inclusion of short exposure studies may lead to an exaggerated risk for myocardial infarction in this population. CONCLUSIONS: In the presence of observational study designs, prior to synthesis, investigators should carefully consider whether all studies at hand are able to answer the same clinical question. The potential for a quantitative synthesis should be guided through examination of the amount of clinical and methodological heterogeneity and assessment of possible biases.