Research question 1

How OR models can be designed, developed, and validated to provide an improved understanding of the earlier treatment benefits on patients’ life-time outcome for two different treatment interventions in hyperacute stroke care system?

To address this research question, we first conducted a literature review in Chapter 2 of this thesis using different search methodologies to find OR stroke related studies reported in OR/MS and clinical literature. We then adopted a conceptual framework proposed by Churilov and Donnan (2012) to classify the papers identified as a result of this literature review in relation to both the specific parts of the stroke care system (problem area) being addressed and the nature and purpose of the OR intervention.

Even though OR models have been applied successfully by researchers to address different problems in the stroke care system, prior to the research reported in this thesis, there was no OR model used to measure the population benefits due to earlier provision of IV tPA and endovascular thrombectomy treatments for the stroke patients. In Chapter 4 of this thesis, we designed and developed two OR models, namely the ‘IV tPA’ and the ‘Endovascular Thrombectomy’ models, used to investigate the gained population benefits associated with existing treatment interventions for the stroke patients.

6.1.1 Findings

As a result of literature review classification conducted in Chapter 2, we concluded that OR interventions such as stroke care process design and performance, stroke team scheduling and workforce planning, and stroke service planning were addressed more frequently than other interventions, while there was a lack of research attention in using stroke units, imaging and surgical equipment evaluation and selection models OR interventions to address different problems in the stroke care system. With regard to different problem areas, stroke prevention, pre-hospital, stroke unit care, rehabilitation and social and community

160 care fields were among the most addressed areas; while information and support for stroke patients, appropriate management of TIAs, appropriate stroke care expertise, and financial viability were among the least addressed areas in the literature.

As a result of the ‘IV tPA’ and the ‘Endovascular Thrombectomy’ models developed in Chapter 4, we found that few minutes of earlier treatment in delivering IV tPA and endovascular thrombectomy can be translated into days, weeks, and even months of healthy- life for stroke patients. Following is the list of findings for these OR models:

 Both models are categorized as models for investigation and improvement according to Pidd (2010) taxonomy as they are used to provide insights on the effect of time delays associated with IV tPA and endovascular thrombectomy treatment interventions on patients’ life time outcomes

 One minute earlier of IV tPA treatment time provides on average extra 1.8 days of healthy life for the stroke patients; while one minute earlier of endovascular thrombectomy provides on average extra 3.2 days of healthy life for the stroke patients. Thus, it was concluded that faster treatment is even more important in the endovascular therapy.

 For both IV tPA and endovascular thrombectomy treatment interventions, female and young patients benefit more by earlier treatment due to their longer lifetime.

6.1.2 Contributions and implications

The literature review conducted in Chapter 2 demonstrated the extent of stroke related OR studies reported in OR/MS literature by different authors and how these studies have used OR interventions to address specific problem areas in the hyperacute stroke care system. The result of this literature review was partially published in a conference paper “Stroke care systems: can simulation modelling catch up with the recent advances in stroke treatment?”, in 2015 in the Proceedings of Winter Simulation Conference (Keshtkaran, et al., 2015).

The ‘IV tPA’ model developed in this research, was the first OR model used for investigating the benefits of faster access to IV tPA treatment on patients’ life-time outcomes. Findings of this model had significant impacts on increasing the awareness of the public policy decision makers on the importance of faster delivery of the IV tPA treatment to stroke patients. The non-technical overview of this model was presented for a clinical audience in 2014 in the leading journal of the field, Stroke, titled “Stroke thrombolysis; save a minute, save a day”(Meretoja, et al., 2014). Since its publication, this article has been cited more than 60 times according to Scopus database, at the time of submitting this thesis. This

161 publication led to a significant media exposure including sources like Bloomberg (Gale, 2014), the Times (Whipple, 2014), Reuters (Seaman, 2014), Herald Sun (2014), and ABC national television news in Australia (ABC News 24, 2014). Moreover, American Heart and Stroke associations produced an infographics encapsulating the findings for the consumers (American Heart Association/American Stroke Association, 2014). The model’s findings are also used by the Australian National Stroke Foundation and Victorian Stroke Telemedicine Initiative (State of Victoria, Australia) to advocate for wider use of stroke thrombolysis telemedicine in remote and rural areas (Bladin & Cadilhac, 2014).

Similarly, the ‘Endovascular Thrombectomy’ model developed in this research, was the first OR model used for investigating the benefits of earlier access to endovascular thrombectomy therapy on patients’ life-time outcomes, thus, advocating for the importance of equipping the clinical centres with necessary expertise and facilities for faster delivery of this intervention to stroke patients. The non-technical overview of the ‘Endovascular Thrombectomy’ model has been accepted for publication in Neurology journal (Meretoja, et al., 2017) and authors expect to receive considerable interest by researchers and clinicians by its publication. Both ‘IV tPA’ and ‘Endovascular Thrombectomy’ models were validated using the generic validation framework developed in Chapter 3; thus, providing an improved confidence for decision makers to use the recommendation proposed by these models. Discussion on validation of these OR models is provided in Section 6.3 of this chapter in addressing the third research question of this thesis.

6.1.3 Limitations of the research and future directions

Since data used to develop the ‘IV tPA’ and the ‘Endovascular Thrombectomy’ models were obtained from different clinical centres and potentially different countries, caution should be exercised before generalizing the results for different populations of stroke patients. To build the ‘Endovascular Thrombectomy’ treatment, we assumed an average 90 minutes delay between the IV tPA and thrombectomy treatments. In Chapter 4, we validated the outputs of the model to ensure the validity of this delay time parameter used to build the model, however it should be noted that in practice this delay time can be shorter or longer for different clinical centres.

Given the significant effect of small treatment time reductions on patients’ lifetime outcomes, further research is needed to investigate how different OR interventions can be employed to further reduce treatment delay times in the hyperacute stroke care system. This can be achieved by using a system approach and continuous improvement practices to shorten both the pre-hospital and in-hospital delays (Fonarow, et al., 2011; Köhrmann, et al.,

162 2011; Meretoja & Kaste, 2012; Meretoja, et al., 2012; Tilley, et al., 1997). Furthermore, few studies have reported on the effectiveness of using the portable Computed Tomography (CT) vehicles and point-of-care laboratories in reducing treatment delay times upon the availability of these services for the hyperacute stroke care system (Walter, et al., 2012; Weber, et al., 2013). Since application of such services implies significant capital investment and personnel training for the system, it is necessary to conduct the cost-effectiveness analysis before promoting the practice change by use of these services. Results obtained by the ‘IV tPA’ and ‘Endovascular Thrombectomy’ models developed in this thesis can be used as model inputs to evaluate the feasibility of these services.