Operations research models for investigation and improvement of the hyperacute stroke care system

Stroke is the third most common cause of death and the sixth major cause of disability around the world with ischemic stroke accounting for around 80% of all strokes. It has been clinically indicated in treating ischemic stroke patients that maximum benefits can be achieved with the speediest arterial recanalization by effective and fast application of existing acute therapies. These therapies comprise either (1) dissolving the blood clot using Intravenous Tissue Plasminogen Activator (IV tPA) treatment or (2) physically removing the clot from the artery using endovascular thrombectomy treatment. These treatments should be performed within the hyperacute time window of 6 hours from stroke onset. For nearly two decades until late 2014, the intravenous thrombolysis delivered to patients was the most effective treatment for stroke patients. This was administrated within a maximum of 4.5 hours from stroke onset. In early 2015, results of five clinical trials from different parts of the world demonstrated the effectiveness of the endovascular thrombectomy therapy. This was provided within 6 hours of stroke onset for the eligible stroke patients who already have received thrombolysis treatment. Research presented in this thesis is the first attempt to quantify the link between the earlier treatment and long-term benefits for the hyperacute stroke patients. Moreover, with the gradual emergence of new evidence about effectiveness of the endovascular thrombectomy treatment in the hyperacute stroke care systems, new questions were raised in the clinical literature since not all hospitals have the expertise and equipment required for delivering the endovascular thrombectomy treatment. Some of the most burning questions were formulated in an Editorial article published in the Journal of the American Medical Association (JAMA) by Warach and Johnson (2016). These questions mainly concern the issue of treatment pathway selection between two groups of hospitals with different facilities and expertise to support new investigations in the hyperacute stroke care system by comparing the long-term benefits for individual patients. This research demonstrates how Operations Research (OR) models can be used to answer these and other questions in the hyperacute stroke care system. It is specifically focused on OR models for investigation and improvement to provide better understanding of the complex decisions arising in the hyperacute stroke care system. The main aimof this thesis is to investigate the issue of design, development and validation of OR models used for investigation and improvement of the hyperacute stroke care system. Thus, this work addresses very recent and important questions in the field to support more effective and efficient provision of the services to stroke patients. Three OR models for investigation and improvement are designed and validated in this thesis: (1) ’IV tPA’ model, (2) ‘Endovascular Thrombectomy’ model, and (3) ‘Individual Patient’ model. The first two OR models are used to provide an understanding of the long-term population benefits of faster access to stroke treatment interventions. Based on the first two OR models, one minute earlier of IV tPA and endovascular thrombectomy interventions respectively on average provide 1.8 days and 3.2 extra days of healthy life for the stroke patients. The third OR model is used to provide assistance with maximizing the individual patient’s life-time benefits over two pathways of the hyperacute stroke care system. Finally, we present a novel validation framework that is used to validate all three OR models developed in this thesis. This research contributes to OR/MS literature by design, development and validation of OR models used to provide an improved understanding of the long-term population and individual patient’s benefits due to faster delivery of stroke treatment interventions in the hyperacute stroke care system. A discussion on the validation of OR models is also novel and further addresses the existing gaps in OR/MS literature