Understanding power in randomized trials: The example of vertebroplasty.

OBJECTIVES: Randomized trials (RCTs) should include a sufficient number of patients to reduce the risk that the observed outcome is a result of chance rather than from a truly different treatment effect. Trials must be even larger to claim an absence of treatment effect in a placebo-controlled trial. To estimate the size of the trial and maximize power, it is often suggested to use a comparison between the means of a continuous variable. METHODS: We examine the RCTs that have compared vertebroplasty and placebo for patients with osteoporotic fractures. Most trials compared the means of a continuous pain score to yield implausibly small trials, as small as 24 patients per group. RESULTS: The minimally significant difference between groups has no precise clinical meaning for patients when it is based on a comparison of means of pain scores. A comparison of the proportions of patients reaching a per-patient outcome measure of treatment success is much more pertinent if the trial is to inform the care of future patients. The resulting trials will admittedly need to be larger, but they will be much less likely to fall prey to the 'evidence of absence' fallacy. Furthermore, trial size should also take into consideration harder clinical outcome measures, such as death and disability. CONCLUSION: When the goal of a trial is to inform outcome-based medical care, comparing the proportions of patients reaching a clinically pertinent outcome is more appropriate than comparing the means of a continuous variable.

Understanding explanatory and pragmatic trials: Examples from randomized controlled trials on vertebroplasty.

OBJECTIVES: To better understand the explanatory-pragmatic distinction in the design and interpretation of randomized controlled trials (RCTs). METHODS: We review the explanatory-pragmatic distinction in clinical trial design. We use the PRECIS-2 tool to evaluate the trial design of selected RCTs on percutaneous vertebroplasty for osteoporotic vertebral compression fractures. We discuss difficulties in the selection of criteria and in the construction of PRECIS diagrams. We also examine how inconsistency in the selection of various items of trial design can cause confusion in the interpretation of results. RESULTS: The selection of criteria and the scoring of multiple PRECIS domains were subjective and thus debatable. The pragmascope patterns of various vertebroplasty trials were heterogeneous. Many trials had both pragmatic and explanatory components. Some placebo-controlled trial goals seem to have been explanatory, but their design actually included enough pragmatic items such that the meaning of negative trial results remains ambiguous. CONCLUSION: The results of a trial cannot be interpreted without understanding the various design choices made along the explanatory-pragmatic spectrum.

Understanding the choice of control group: A systematic review of vertebroplasty trials for osteoporotic vertebral compression fractures.

OBJECTIVES: To better understand the choice of the comparator intervention in the design of clinical trials and its impact on the meaning of results we review randomized trials on vertebroplasty. METHODS: We conducted a systematic and narrative review of all randomized trials on vertebroplasty. Trials are categorized according to the comparator intervention (non-surgical management, placebo/sham vertebroplasty, and kyphoplasty). RESULTS: All trials were too small to show a difference in objective clinical outcomes, and 20 of 23 RCTs used mean pain scores to compare interventions. Most trials comparing vertebroplasty with non-surgical management concluded that vertebroplasty was superior. Trials comparing kyphoplasty with vertebroplasty showed similar results for both interventions. However, 4 of 5 trials comparing vertebroplasty with placebo surgery failed to show a significant difference between groups. CONCLUSION: The clinical results of an intervention cannot be interpreted without a comparison that involves a control group. The choice of comparator intervention can change the meaning of the trial. A large pragmatic trial, using hard clinical outcomes such as morbidity and mortality as a primary outcome measure, would be needed to assess the potential clinical benefits of vertebroplasty.

Successful Reperfusion is Associated with Favorable Functional Outcome despite Vessel Perforation during Thrombectomy: A Case Series and Systematic Review.

BACKGROUND: Arterial perforation is a potentially serious complication during endovascular thrombectomy. PURPOSE: Our aim was to describe interventional approaches after arterial perforation during endovascular thrombectomy and to determine whether reperfusion remains associated with favorable outcome despite this complication. DATA SOURCES: Data from consecutive patients with acute stroke undergoing endovascular thrombectomy were retrospectively collected between 2015 to 2020 from a single-center cohort, and a systematic review was performed using PubMed, EMBASE, and Ovid MEDLINE up to June 2020. STUDY SELECTION: Articles reporting functional outcome after arterial perforation during endovascular thrombectomy were selected. DATA ANALYSIS: Functional outcomes of patients achieving successful reperfusion (TICI 2b/3) were compared with outcomes of those with unsuccessful reperfusion in our single-center cohort. We then summarized the literature review to describe interventional approaches and outcomes after arterial perforation during endovascular thrombectomy. DATA SYNTHESIS: In our single-center cohort, 1419 patients underwent endovascular thrombectomy, among whom 32 (2.3%) had vessel perforation and were included in the analysis. The most common hemostatic strategy was watchful waiting (71% of cases). Patients with successful reperfusion had a higher proportion of favorable 90-day mRS scores (60% versus 12.5%; P = .006) and a lower mortality rate (13.3% versus 56.3%, P = .01) than patients without successful reperfusion. Thirteen articles were included in the systematic review. Successful reperfusion also appeared to be associated with better outcomes. LIMITATIONS: Given the low number of published reports, we performed only a descriptive analysis. CONCLUSIONS: Arterial perforation during endovascular thrombectomy is rare but is associated with high mortality rates and poor outcome. However, successful reperfusion remains correlated with favorable outcome in these patients.