Medical therapy, radiofrequency ablation or cryoballoon ablation as first-line treatment for paroxysmal atrial fibrillation: interpreting efficacy through restricted mean survival time and network meta-analysis.

When multiple treatments are available, network meta-analysis can evaluate data to rank the relative effectiveness. We applied this approach to first-line treatments for paroxysmal atrial fibrillation (medical therapy, radiofrequency ablation or cryoballoon ablation). Individual trials were analysed based on the restricted mean survival time (RMST). Randomised controlled trials (RCT) assessing first-line treatments for paroxysmal atrial fibrillation were referenced from PubMed and the websites of regulatory agencies. The primary end-point was atrial fibrillation recurrence-free survival at 12 months. The treatments assessed for their relative effectiveness were medical therapy, radiofrequency ablation and cryoballoon ablation. Individual trials were examined based on RMST. A Bayesian network meta-analysis was conducted to comparatively evaluate these treatments. Five trials were included in the analysis: two compared radiofrequency with medical treatment and three cryoballoon ablation with medical treatment. The indirect comparison of radiofrequency ablation vs cryoballoon ablation was assessed in the absence of RCTs. Differences in RMST (with 95% credible intervals) were estimated for all binary comparisons (direct or indirect). Radiofrequency and cryoballoon ablation showed significantly increased effectiveness compared with medical treatment. In the indirect comparison, radiofrequency showed a non-significant advantage over cryoballoon ablation. The ranking of effectiveness was as follows: (1) radiofrequency; (2) cryoballoon ablation; (3) medical treatment. In conclusion, we found that radiofrequency was the most effective treatment for paroxysmal atrial fibrillation according to a Bayesian probabilistic model.

Simplified figure to present direct and indirect comparisons: Revisiting the graph 10 years later.

A "simplified" figure was proposed in 2011 to summarize the results of controlled trials that evaluate different treatments aimed at the same disease condition. The original criteria for classifying individual binary comparisons included superiority, inferiority and no significance difference; hence, they did not differentiate between no proof of difference vs proof of no difference. We updated the criteria employed in the original "simplified" figure in order to include this differentiation. A revised version of the simplified figure is proposed and described herein. An example of application is also presented. The example is focused on first-line treatments for paroxysmal atrial fibrillation. Three treatments (medical therapy, cryoballoon ablation, radiofrequency ablation) are compared with one another through direct and indirect comparisons.

First-line treatments for chronic lymphocytic leukemia: Analysis of 7 trials based on the restricted mean survival time.

OBJECTIVE: The purpose of this study was to assess the effectiveness of the newest first-line treatments for chronic lymphocytic leukemia (CLL), used alone or in combination, in comparison with standard treatments. MATERIALS AND METHODS: We selected 15 cohorts of patients published in 7 clinical trials. The restricted mean survival time (RMST) was used for analyzing survival curves, performing the comparisons and ranking the treatments based on their effectiveness. The endpoint was progression-free survival (PFS). RESULTS: 15 patient cohorts receiving 11 different first-line treatments were studied. Overall, all of the newest treatments had a positive effect on PFS compared with the old standards. As compared with chlorambucil monotherapy, the improvement in PFS resulting from targeted therapies ranged from 5.4 to 7.3 months per patient. Excluding chlorambucil alone or combined with obinutuzumab, the remaining 11 targeted treatments showed nearly identical values of PFS. Numerically but not statistically, ibrutinib plus venetoclax was associated with the longest PFS. Post-hoc pairwise comparisons were calculated to better interpret these results. CONCLUSION: Our results provide an updated overview of the efficacy of the newest first-line treatments for CLL. Our findings confirm the good performance of RMST in this type of analyses.

Reduced habit-driven errors in Parkinson's Disease.

Parkinson's Disease can be understood as a disorder of motor habits. A prediction of this theory is that early stage Parkinson's patients will display fewer errors caused by interference from previously over-learned behaviours. We test this prediction in the domain of skilled typing, where actions are easy to record and errors easy to identify. We describe a method for categorizing errors as simple motor errors or habit-driven errors. We test Spanish and English participants with and without Parkinson's, and show that indeed patients make fewer habit errors than healthy controls, and, further, that classification of error type increases the accuracy of discriminating between patients and healthy controls. As well as being a validation of a theory-led prediction, these results offer promise for automated, enhanced and early diagnosis of Parkinson's Disease.