On clinical trial fragility due to patients lost to follow up

Wells ′ research was partially supported by NIH grant U19 AI111143, PCORI IHS-2017C3-8923, and Cornell’s Center for the Social Sciences project on Algorithms, Big Data, and Inequality.Background Clinical trials routinely have patients lost to follow up. We propose a methodology to understand their possible effect on the results of statistical tests by altering the concept of the fragility index to treat the outcomes of observed patients as fixed but incorporate the potential outcomes of patients lost to follow up as random and subject to modification. Methods We reanalyse the statistical results of three clinical trials on coronary artery bypass grafting (CABG) to study the possible effect of patients lost to follow up on the treatment effect statistical significance. To do so, we introduce the LTFU-aware fragility indices as a measure of the robustness of a clinical trial’s statistical results with respect to patients lost to follow up. Results The analyses illustrate that clinical trials can either be completely robust to the outcomes of patients lost to follow up, extremely sensitive to the outcomes of patients lost to follow up, or in an intermediate state. When a clinical trial is in an intermediate state, the LTFU-aware fragility indices provide an interpretable measure to quantify the degree of fragility or robustness. Conclusions The LTFU-aware fragility indices allow researchers to rigorously explore the outcomes of patients who are lost to follow up, when their data is the appropriate kind. The LTFU-aware fragility indices are sensitivity measures in a way that the original fragility index is not.Peer reviewe

An optimal control approach to determine resistance-type boundary conditions from in-vivo data for cardiovascular simulations

The choice of appropriate boundary conditions is a fundamental step in computational fluid dynamics (CFD) simulations of the cardiovascular system. Boundary conditions, in fact, highly affect the computed pressure and flow rates, and consequently haemodynamic indicators such as wall shear stress (WSS), which are of clinical interest. Devising automated procedures for the selection of boundary conditions is vital to achieve repeatable simulations. However, the most common techniques do not automatically assimilate patient-specific data, relying instead on expensive and time-consuming manual tuning procedures. In this work, we propose a technique for the automated estimation of outlet boundary conditions based on optimal control. The values of resistive boundary conditions are set as control variables and optimized to match available patient-specific data. Experimental results on four aortic arches demonstrate that the proposed framework can assimilate 4D-Flow MRI data more accurately than two other common techniques based on Murray's law and Ohm's law

Tackling challenges of global health electives: Resident experiences of a structured and supervised medicine elective within an existing global health partnership

Background: The Toronto-Addis Ababa Academic Collaboration in Emergency Medicine (TAAAC-EM) deploys teaching teams of Canadian EM faculty to Addis Ababa to deliver a longitudinal residency curriculum. Canadian trainees participate in these teams as a formally structured and supervised elective in global health (GH) and EM, which has been designed to enhance the strength of GH electives and address key challenges highlighted in the literature.Methods: The purpose of this qualitative study was to identify, describe, and evaluate strengths and weaknesses of this elective in relation to its purposeful structure. Residents who completed the elective were invited to participate in face-to-face interviews to discuss their experiences.Results: The findings show that the residents both chose this elective because of its purposefully designed features, and that these same features increased their enjoyment and the educational benefit of the elective. Supervised bedside teaching, relationships shared with Ethiopian residents, and the positive impact the experience had on their clinical practice in Canada were identified as the primary strengthsConclusion: Purposeful and thoughtful design of global health electives can enhance the resident learning experience and mitigate challenges for trainees seeking global health training opportunities

Disagreement Between Randomized and Observational Evidence on the Use of Bilateral Internal Thoracic Artery Grafting:A Meta-Analytic Approach

Background The ART (Arterial Revascularization Trial) showed no difference in survival at 10 years between patients assigned to the single versus bilateral internal thoracic artery grafting strategies. This finding is in contrast with the results of most observational studies, where the use of 2 internal thoracic arteries has been associated with improved survival. Methods and Results We selected propensity-matched studies from the most comprehensive observational meta-analysis on the long-term outcomes of patients receiving 1 versus 2 internal thoracic arteries. Individual participant survival data from each study and the ART were reconstructed using an iterative algorithm that was applied to solve the Kaplan-Meier equations. The reconstructed individual participant survival data were aggregated to obtain combined survival curves and Cox regression hazard ratios with 95% CIs. Individual participant survival data were obtained from 14 matched observational studies (24 123 patients) and the ART. The 10-year survival of the control group of ART was significantly higher than that of the matched observational studies (hazard ratio, 0.86; 95% CI, 0.80-0.93). The 10-year survival of the experimental group of ART was significantly lower than that of the bilateral internal thoracic artery group of the observational studies (hazard ratio, 1.11; 95% CI, 1.03-1.20). Conclusions Both the improved outcome of the control arm and the lower beneficial effect of the intervention had played a role in the difference between observational evidence and ART