Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials

Abstract

Brain arteriovenous malformations (AVMs) are a heterogeneous group of rare lesions that can pre sent with headaches, seizures, neurological deficits, and intracranial hemorrhages. Risks of hemorrhage have been estimated in the range of 2%-4% per year. 8,15,32,47 Risk factors for future ruptures have been identified, but their use to inform decision making is errorprone, given the methodological problems with AVM observational studies and the modest relative risks. The comments were categorized as items related to the design, the conduct, and the analysis and interpretation of the trial. results Thirty-one articles or letters were identified. The pragmatic design, with heterogeneity of patients and lack of standardization of the treatment arm, were frequently stated concerns. The choice of outcome measures was repeatedly criticized. During the trial, low enrollment rates, selection bias, and premature interruption of enrollment were frequent comments. The short follow-up period, the lack of subgroup analyses, the lack of details on the results of the various treatments, and a contentious interpretation of results were noted at the analysis stage. A fundamental problem was the primary hypothesis testing conservative management. The authors believe that other trials are needed. Future trials could be pragmatic, test interventions stratified at the time of randomization, and look for long-term, hard clinical outcomes in a large number of patients. coNclusioNs In the authors' view, the ARUBA trial is a turning point in the history of brain AVM management; future trials should aim at integrating trial methodology and clinical care in the presence of uncertainty.

Advocating Intraluminal Radiation Therapy in Cerebral Arteriovenous Malformation Treatment

“…Some, that were relatively more supportive, identified ARUBA as the only randomized trial at that time (2010) with clear clinical outcomes comparing different interventional treatments for brain AVMs with conservative medical therapy [100]. More reactions were less supportive, criticizing the pragmatic design, the patients' heterogeneity, the lack of standardization of the treatment arm, the choice of outcome measures, the short follow-up period, the small population, and so forth [87,101,102]. The controversy also led the European societies dealing with the treatment of AVMs to conduct a consensus conference at the European level [104].…”

Combined surgical treatment of the cerebral arteriovenous malformations in patients with the torpid course of the disease

“…Клиническая манифестация чаще всего наступает в возрасте до 40 лет [1,2] и примерно в половине случаев АВМ проявляется кровоизлиянием [3,4]. Риск ежегодного развития кровоизлияния из неразорвавшейся АВМ -2-4 % в год [5][6][7]. Летальность при первом кровоизлиянии составляет 10-30 %, инвалидизация -50 % [8,9].…”

Editorial. FIAT, flow diverters, and establishing the role of new technology

“…This is the crux of the contrast between explanatory and pragmatic trials that we have reviewed elsewhere. 2 It is unclear what the authors wish to do with heterogeneity. Multiply an increasing number of trials with narrow selection criteria of an already uncommon condition?…”

“…Flow diverters have a well-established learning curve and the relative rarity of lesions amenable to flow diversion makes the accumulation of significant experience challenging. 2 There were no criteria established to permit inclusion of practitioners or centers in the study, yet all operators had performed at least 10 flow diversion cases prior to entry. Although care studies are designed to protect patients from learning curves, it should be remembered that flow diversion is no longer so new that there are a limited number of practitioners employing the devices.…”