The effects of stenting and endothelial denudation on experimental aneurysm healing and gene expression following endovascular treatment

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials

The trial on endovascular management of unruptured intracranial aneurysms (TEAM), a prospective randomized trial comparing coiling and conservative management, initiated in September 2006, was stopped in June 2009 because of poor recruitment (80 patients). Aspects of the trial design that may have contributed to this failure are reviewed in the hope of identifying better ways to successfully complete this special type of pragmatic trial which seeks to test two strategies that are in routine clinical use. Cultural, conceptual and bureaucratic hurdles and difficulties obstruct all trials. These obstacles are however particularly misplaced when the trial aims to identify what a good medical practice should be. A clean separation between research and practice, with diverging ethical and scientific requirements, has been enforced for decades, but it cannot work when care needs to be provided in the presence of pervasive uncertainty. Hence valid and robust scientific methods need to be legitimately re-integrated into clinical practice when reliable knowledge is in want

The small trial problem

Abstract Background Many randomized trials that aim to assess new or commonly used medical or surgical interventions have been so small that the validity of conclusions becomes questionable. Methods We illustrate the small trial problem using the power calculation of five Cochrane-reviewed studies that compared vertebroplasty versus placebo interventions. We discuss some of the reasons why the statistical admonition not to dichotomize continuous variables may not apply to the calculation of the number of patients required for trials to be meaningful. Results Placebo–controlled vertebroplasty trials planned to recruit between 23 and 71 patients per group. Four of five studies used the standardized mean difference of a continuous pain variable (centimeters on the visual analog scale (VAS)) to plan implausibly small trials. What is needed is not a mean effect at the population level but a measure of efficacy at the patient level. Clinical practice concerns the care of individual patients that vary in many more respects than the variation around the mean of a single selected variable. The inference from trial to practice concerns the frequency of success of the experimental intervention performed one patient at a time. A comparison of the proportions of patients reaching a certain threshold is a more meaningful method that appropriately requires larger trials. Conclusion Most placebo-controlled vertebroplasty trials used comparisons of means of a continuous variable and were consequently very small. Randomized trials should instead be large enough to account for the diversity of future patients and practices. They should offer an evaluation of a clinically meaningful number of interventions performed in various contexts. Implications of this principle are not specific to placebo-controlled surgical trials. Trials designed to inform practice require a per-patient comparison of outcomes and the size of the trial should be planned accordingly

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

International audienc

A randomized pragmatic care trial on endovascular acute stroke interventions (EASI): criticisms, responses, and ethics of integrating research and clinical care

Abstract Background The Endovascular Acute Stroke Intervention (EASI) trial was conceived as a pragmatic care trial, designed to integrate trial methods with clinical practice. Reporting the EASI experience was met with objections and criticisms during peer review concerning both scientific and ethical issues. Our goal is to discuss these criticisms in order to promote the pragmatic approach of care trials in outcome-based medical care. Methods The comments and criticisms of 11 reviewers from 5 journals were collected and analyzed. The EASI protocol was also compared to the protocols of seven thrombectomy trials using the pragmatic-explanatory continuum indicator summary (PRECIS). Results Main criticisms of EASI concerned selection criteria that were judged to be too vague and too inclusive, brain and vascular imaging methods that were not sufficiently prescribed by protocol, lack of blinding of outcome assessment, and lack of power. EASI was at the pragmatic end of the spectrum of thrombectomy trials. Conclusion The pragmatic care trial methodology is not currently well-established. More work needs to be done to integrate scientific methods and ethical care in the best medical interest of current patients