In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials

Abstract Although the cost of clinical trials is ever-increasing, in-silico trials, which rely on virtual populations and interventions simulated using patient-specificc models, may offer a solution to contain these costs. However, in-silico trial endpoints need to be compared to those available from conventional clinical trials to ensure that the predictions of safety or effcacy from the in-silico approach are valid. Here, we present the flow diverter performance assessment (FDPASS) in-silico trial, which modelled the treatment of intracranial aneurysms in 82 virtual patients with a flow-diverting stent, using computational fluid dynamics (CFD) to quantify post-treatment flow reduction in the aneurysm sac. The predicted FD-PASS flow-diversion success rate replicated the values previously reported in three reference clinical trials. The in-silico approach allowed broader investigation of factors associated with insuficient flow reduction and increased stroke risk after flow diversion than would be feasible in a conventional trial. These ndings demonstrate for the rst time that in-silico trials of medical devices can (i) replicate ndings of conventional clinical trials and (ii) incorporate virtual experiments that are impossible in conventional trials.

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In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials

Nature Communications ◽

10.1038/s41467-021-23998-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ali Sarrami-Foroushani ◽

Toni Lassila ◽

Michael MacRaild ◽

Joshua Asquith ◽

Kit C. B. Roes ◽

...

Keyword(s):

Clinical Trials ◽

In Silico ◽

Flow Diverter ◽

Patient Specific ◽

Success Rates ◽

Virtual Experiments ◽

Flow Reduction ◽

The Cost ◽

Flow Diverting Stent ◽

Flow Diverters

AbstractThe cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.

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A Novel Flow Diverter for Direct Treatment of Cerebral Aneurysms

Volume 3: 16th International Conference on Advanced Vehicle Technologies; 11th International Conference on Design Education; 7th Frontiers in Biomedical Devices ◽

10.1115/detc2014-35699 ◽

2014 ◽

Author(s):

Jiayao Ma ◽

Thomas Peach ◽

Zhong You ◽

Rafik R. Rizkallah ◽

James Byrne

Keyword(s):

In Silico ◽

Cerebral Aneurysms ◽

Flow Diverter ◽

Flow Reduction ◽

Direct Treatment ◽

In Vivo Testing ◽

Biological Reaction ◽

Aneurysm Model ◽

Flow Diverting Stent

A summary of the manufacturing, in-silico and in-vivo testing of a laser cut cerebral flow-diverting stent (FDS) prototype is presented. The predicted flow-reduction achieved by both variants of the FDS design compares favorably with current commercially available designs. FDS design II is implanted into a swine aneurysm model to validate both the flow-diverting capability and a lack of adverse biological reaction.

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Computational Study of Hemodynamic Changes Induced by Overlapping and Compacting of Stents and Flow Diverter in Cerebral Aneurysms

Frontiers in Neurology ◽

10.3389/fneur.2021.705841 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sunghan Kim ◽

Hyeondong Yang ◽

Ineui Hong ◽

Je Hoon Oh ◽

Yong Bae Kim

Keyword(s):

Computational Study ◽

Cerebral Aneurysms ◽

Flow Diverter ◽

Flow Diversion ◽

Cfd Analysis ◽

Hemodynamic Parameters ◽

Intracranial Stent ◽

Low Profile ◽

Computational Fluid Dynamics Cfd ◽

Aneurysm Model

Purpose: The flow diversion effect of an intracranial stent is closely related to its metal coverage rate (MCR). In this study, the flow diversion effects of Enterprise and low-profile visualized intraluminal support (LVIS) stents are compared with those of a Pipeline flow diverter, focusing on the MCR change. Moreover, the changes in the flow diversion effect caused by the additional manipulations of overlapping and compaction are verified using computational fluid dynamics (CFD) analysis.Methods: CFD analysis was performed using virtually generated stents mounted in an idealized aneurysm model. First, the flow diversion effects of single Enterprise, LVIS, and Pipeline devices were analyzed. The Enterprise and LVIS were sequentially overlapped and compared with a Pipeline, to evaluate the effect of stent overlapping. The effect of compacting a stent was evaluated by comparing the flow diversion effects of a single and two compacted LVIS with those of two overlapped, uncompacted LVIS and uncompacted and compacted Pipeline. Quantitative analysis was performed to evaluate the hemodynamic parameters of energy loss, average velocity, and inflow rate.Results: Statistically significant correlations were observed between the reduction rates of the hemodynamic parameters and MCR. The single LVIS without compaction induced a reduction in all the hemodynamic parameters comparable to those of the three overlapped Enterprise. Moreover, the two overlapped, uncompacted LVIS showed a flow diversion effect as large as that induced by the single uncompacted Pipeline. Compacted stents induced a better flow diversion effect than uncompacted stents. The single compacted LVIS induced a flow diversion effect similar to that induced by the two uncompacted LVIS or single uncompacted Pipeline.Conclusions: The MCR of a stent correlates with its flow diversion effect. Overlapping and compaction can increase the MCR of an intracranial stent and achieve a flow diversion effect as large as that observed with a flow diverter.

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Stroke Prevention in Non-Valvular Atrial Fibrillation

Hämostaseologie ◽

10.1055/s-0038-1659985 ◽

1997 ◽

Vol 17 (03) ◽

pp. 166-169

Author(s):

Judith O’Brien ◽

Wendy Klittich ◽

J. Jaime Caro

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Care Home ◽

Relevant Literature ◽

Clinical Trial Data ◽

Outcome Data ◽

Sensitivity Analyses ◽

Bleeding Events ◽

Discharge Data ◽

The Cost

SummaryDespite evidence from 6 major clinical trials that warfarin effectively prevents strokes in atrial fibrillation, clinicians and health care managers may remain reluctant to support anticoagulant prophylaxis because of its perceived costs. Yet, doing nothing also has a price. To assess this, we carried out a pharmacoe-conomic analysis of warfarin use in atrial fibrillation. The course of the disease, including the occurrence of cerebral and systemic emboli, intracranial and other major bleeding events, was modeled and a meta-analysis of the clinical trials and other relevant literature was carried out to estimate the required probabilities with and without warfarin use. The cost of managing each event, including acute and subsequent care, home care equipment and MD costs, was derived by estimating the cost per resource unit, the proportion consuming each resource and the volume of use. Unit costs and volumes of use were determined from established US government databases, all charges were adjusted using cost-to-charge ratios, and a 3% discount rate was applied to costs incurred beyond the first year. The proportions of patients consuming each resource were estimated by fitting a joint distribution to the clinical trial data, stroke outcome data from a recent Swedish study and aggregate ICD-9 specific, Massachusetts discharge data. If nothing is done, 3.2% more patients will suffer serious emboli annually and the expected annual cost of managing a patient will increase by DM 2,544 (1996 German Marks), from DM 4,366 to DM 6,910. Extensive multiway sensitivity analyses revealed that the higher price of doing nothing persists except for very extreme combinations of inputs unsupported by literature or clinical standards. The price of doing nothing is thus so high, both in health and economic terms, that cost-consciousness as well as clinical considerations mandate warfarin prophylaxis in atrial fibrillation.

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Exploring the Power and the Promise of In Silico Clinical Trials: Possible Applications in COVID-19 Pandemic

SSRN Electronic Journal ◽

10.2139/ssrn.3638283 ◽

2020 ◽

Author(s):

Abdelrahman H. Abdelmoneim ◽

Safinaz I. Khalil ◽

Hiba A. Osman ◽

Ayesan Rewane ◽

Sahar G. Elbage

Keyword(s):

Clinical Trials ◽

In Silico

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In silico imaging clinical trials: cheaper, faster, better, safer, and more scalable

Trials ◽

10.1186/s13063-020-05002-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aldo Badano

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Medical Devices ◽

In Silico ◽

Lessons Learned ◽

Patient Access ◽

High Quality ◽

Virtual Imaging ◽

Regulatory Evaluation

AbstractImaging clinical trials can be burdensome and often delay patient access to novel, high-quality medical devices. Tools for in silico imaging trials have significantly improved in sophistication and availability. Here, I describe some of the principal advantages of in silico imaging trials and enumerate five lessons learned during the design and execution of the first all-in silico virtual imaging clinical trial for regulatory evaluation (the VICTRE study).

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International teleproctoring in neurointerventional surgery and its potential impact on clinical trials in the era of COVID-19: legal and technical considerations

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-017053 ◽

2020 ◽

pp. neurintsurg-2020-017053

Author(s):

Emanuele Orru' ◽

Miklos Marosfoi ◽

Neil V Patel ◽

Alexander L Coon ◽

Christoph Wald ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

High Resolution ◽

Situational Awareness ◽

Flow Diverter ◽

Multiple Sources ◽

Remote Supervision ◽

Angiography Suite ◽

The Us ◽

Travel Restrictions

BackgroundExisting travel restrictions limit the mobility of proctors, significantly delaying clinical trials and the introduction of new neurointerventional devices. We aim to describe in detail technical and legal considerations regarding international teleproctoring, a tool that could waive the need for in-person supervision during procedures.MethodsInternational teleproctoring was chosen to provide remote supervision during the first three intracranial aneurysm treatments with a new flow diverter (currently subject of a clinical trial) in the US. Real-time, high-resolution transmission software streamed audiovisual data to a proctor located in Canada. The software allowed the transmission of images in a de-identified, HIPAA-compliant manner.ResultsAll three flow diverters were implanted as desired by operator and proctor and without complication. The proctor could swap between images from multiple sources and reported complete spatial and situational awareness, without any significant lag or delay in communication. Procedural times and radiologic dose were similar to those of uncomplicated, routine flow diversion cases at our institution.ConclusionsInternational teleproctoring was successfully implemented in our clinical practice. Its first use provided important insights for establishing this tool in our field. With no clear horizon for lifting the current travel restrictions, teleproctoring has the potential to remove the need for proctor presence in the angiography suite, thereby allowing the field to advance through the continuation of trials and the introduction of new devices in clinical practice. In order for this tool to be used safely and effectively, highly reliable connection and high-resolution equipment is necessary, and multiple legal nuances have to be considered.

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