Prehospital CT for early diagnosis and treatment of suspected acute stroke or severe head injury
Health technology assessment|
The aim of this health technology assessment (HTA) is to compare the clinical effectiveness and safety of prehospital CT for early diagnosis and potential prehospital treatment of suspected acute stroke or severe head injury with current practice of diagnosis and treatment carried out after arrival in the hospital.
In Norway, approximately 12,000 persons experience acute stroke each year. Time is a crucial factor in the management of stroke, so rapid admission to a hospital for a computed tomography (CT) scan is recommended.
A mobile stroke unit (MSU), an ambulance equipped with a CT scanner, helps bring the hospital to the patient. Research evidence indicates that, compared with conventional care of acute stroke, MSU care probably leads to:
- reduced time from patient’s first contact with the emergency dispatch center to thrombolysis (treatment with a clot dissolving agent)
- increased number of patients who receive thrombolysis
MSU care may also lead to:
- reduced time from patient’s first contact with the emergency dispatch center to CT imaging
- better functionality at 3 months after stroke.
Our cost- and threshold analysis found that:
One MSU is estimated to cost approximately 6.4 million Norwegian kroner annually. The health gain measured in quality-adjusted life-years (QALYs) was 0.3 per patient receiving thrombolysis through MSU care compared with conventional care. We performed an analysis quantifying the severity criterion by calculating absolute shortfall for patients with acute ischemic stroke who receive conventional care. The results show an absolute shortfall of 5.5 QALYs. We found that the expected cost per QALY is approximately 385,000 Norwegian kroner or lower if one MSU successfully reaches at least 35-40% (145-171) of thrombolysis patients per year.
Stroke is the second leading mortality cause in most Western countries, and a major cause of adult disability. In Norway, approximately 12,000 persons experience acute stroke each year. In 2017, 8,789 cases of acute stroke were recorded in the Norwegian Stroke Registry (covering 86% of acute stroke patients). Head injuries also constitute a large group of patients arriving at the emergency ward, and are the leading cause of death in persons under the age of 44 years. Those considered to have severe injury require urgent admission to a neurosurgical department.
In acute stroke and severe head injuries, it is crucial that the patient is diagnosed and treated as soon as possible ("time is brain"). If acute stroke or severe head injury is suspected, rapid admission to a hospital to undertake a computed tomography (CT) scan is recommended. In stroke caused by blood clots (ischemic stroke or cerebral infarction), thrombolytic treatment should be given as soon as possible, at most within 4.5 hours after the onset of symptoms. In hemorrhagic stroke (bleeding), on the other hand, thrombolytic treatment is contra-indicated as it may cause life-threatening complications. Thus it is crucial to determine as soon as possible the cause of the stroke in order to provide appropriate treatment. In head injuries, CT imaging allows the identification of those patients who require urgent admission to a neurosurgical department.
Prehospital CT, either performed in a mobile stroke unit (ambulance equipped with a CT scanner) or in "a CT scanner station" located outside hospital, is a novel approach that brings the hospital closer to the patient. It seeks to shorten the time to diagnosis and treatment, as well as to determine which treatment facility the patient should be directed to.
The aim of this health technology assessment (HTA) is to compare the clinical effectiveness and safety of prehospital CT for early diagnosis and potential prehospital treatment of suspected acute stroke or severe head injury with current practice of diagnosis and treatment carried out after arrival in the hospital. Furthermore, it seeks to shed light on organizational and health economic consequences related to the implementation of prehospital CT in Norway.
Clinical effectiveness and safety
In absence of eligible systematic reviews and HTAs, we conducted systematic searches for primary studies in a selection of relevant databases and trials registries. We limited the searches to publication year 2010 to present, but no restrictions to study type were applied. Two reviewers independently screened identified references, selected full-text publications that met predefined inclusion criteria, and critically appraised the included studies. Data extraction was performed by one reviewer, and checked by a second reviewer. For four outcomes, we were able to synthesize the findings by means of meta-analyses. For other outcomes, results were presented in tables and text. We assessed the certainty of the evidence for the main clinical outcomes using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). In GRADE, the certainty of the evidence is expressed either as high, moderate, low, or very low, depending on the level of confidence we have in the effect estimates.
Health economic evaluation
We conducted a cost- and threshold analysis, which attempts to elucidate mean incremental cost-effectiveness ratios (ICERs) at different values for proportions of ischemic stroke patients receiving thrombolysis through mobile stroke unit (MSU) care compared to conventional care (use of standard ambulance). This method makes it possible to identify a threshold value for the proportion that is required for the MSU to achieve an ICER of a predefined level. We also calculated absolute shortfall for patients with acute ischemic stroke receiving conventional care in order to classify severity for the relevant patient population. Further, we performed a one-way sensitivity analysis to investigate the impact of the MSU cost parameter. We modified an existing probabilistic Markov decision analytic model for ischemic stroke patients, developed as a part of an HTA on mechanical thrombectomy conducted by the Norwegian Institute of Public Health in 2016. The analyses do not evaluate consequences of introducing MSUs in non-metropolitan parts of Norway, and they do not account for patients with other indications who might benefit from MSU care.
Clinical effectiveness and safety
Searches for primary studies resulted in a total of 2,628 unique records. Of these, 8 publications, representing 4 studies, were considered eligible for inclusion. The studies comprised two randomized controlled trials (RCTs) and one observational registry study from Germany, and a dosimetry (measurements of radiation exposure) study from the U.S. In all of these studies, the intervention consisted of an MSU for stroke.
MSU care reduced the time from alarm to imaging and from alarm to thrombolysis. Based on the study findings, the difference between MSU and conventional care in mean minutes from alarm to CT was around 27 minutes (95% CI -51 to -3) (low certainty of the evidence), and from alarm to thrombolysis around 31 minutes (95% CI -43 to -18) (moderate certainty of the evidence). Similarly, one of the RCTs, investigating time from symptom onset to imaging, detected a reduction in time, in favour of MSU (39 minutes difference in median, 95% CI IQR 26 to 52) (certainty of the evidence not graded). No statistically significant difference between groups in time from symptom onset to thrombolysis was detected (-50 mean minutes, 95% CI -117 to 18) (low certainty of the evidence). However, the effect direction of the two included RCTs investigating this outcome was the same, favouring MSU.
Based on the evidence, in total, 11% more patients received thrombolysis with MSU care, compared to those who received conventional care (32% vs. 21%) (moderate certainty of the evidence). Among those who received thrombolysis, MSU patients were more than five times more likely (31% vs. 5.5%) to receive thrombolysis within 60 minutes (golden hour), than those who received conventional care (low certainty of the evidence). Furthermore, compared to conventional care, MSU care improved triage of patients with stroke to specialized hospitals (certainty of the evidence not graded), and increased the proportion of patients with 3-month modified Rankin Scale (mRS) score 0-3 (low certainty of the evidence). The mRS scale is used to measure physical function and runs from 0 to 6 (0 = no symptoms of disability, 6 = dead).
No differences in 90-day mortality (RR 1.35, 95% CI 0.84 to 2.15) (low certainty of the evidence) or hemorrhagic complications (RR 0.55, 95% CI 0.23 to 1.34) (certainty of the evidence not graded) were detected. Radiation exposure for MSU staff or the public did not exceed established dose limits.
We were not able to identify studies investigating the effectiveness of CT scanners localized in decentralized CT stations outside hospitals, or the use of prehospital CT in suspected severe head injuries.
Health economic evaluation
The estimated annual cost of one MSU is approximately 6.4 million Norwegian kroner, and includes both daily operation- and depreciation costs on the investment. The health economic model simulation resulted in a quality-adjusted life-year (QALY) gain of 0.3 per patient who received thrombolysis through MSU care compared with conventional care. We calculated an absolute shortfall of 5.5 QALYs. We found that the expected cost per QALY is about 385,000 Norwegian kroner or lower if one MSU successfully reaches at least 35-40% (145-171) of thrombolysis patients per year. We assume that efficacy results are transferable to metropolitan areas in Norway. Our one-way sensitivity analyses indicate that the required patient proportion to achieve an incremental cost-effectiveness ratio (ICER) of 385,000 Norwegian kroner would decrease when the MSU costs decrease and increase when the MSU costs increase.
Based on the findings presented in this HTA, MSU care probably shortens the time to imaging and treatment, and results in higher frequency of thrombolysis administration. The included studies took place in two larger cities in Germany. We assume that the effectiveness of MSU care could be, to some extent, transferrable to metropolitan areas of Norway. However, the degree to which these outcomes can be achieved depends on several context-specific factors. Thus, it will require local adaptations of processes and workflow, and a close cooperation between emergency dispatch center, hospitals, MSUs and regular ambulances. Furthermore, issues related to MSU staffing and required competence, as well as use of telemedicine, must be considered.
To ensure that equal healthcare is offered to the entire population in Norway, different options may need to be considered in rural and remote areas. “A rendezvous model” where an MSU travels to meet the incoming ambulance or helicopter, or establishment of CT stations outside hospitals, such as the CT scanner currently placed in the district medical center in Ål, are some alternatives to consider. However, robust studies are needed to determine the effectiveness of these options.
While producing this HTA, we identified five ongoing studies with estimated completion dates within the next few years. Two of these studies are conducted in Norway. One is a prospective controlled intervention study on MSU care, taking place in Østfold, with 400 participants. The other is an observational study on rural CT examination and thrombolytic treatment for stroke (CT station in Ål), with 200 participants. The estimated completion dates for these studies are May and April 2021, respectively.
It must be emphasized that prehospital CT represents a supplementary tool to increase the efficiency of stroke management, and cannot replace any other efforts to improve intrahospital and prehospital stroke management. In Norway, the dispatch guidelines (index) used by the emergency medical communication centers (EMCCs) are known to identify just over half of the acute stroke patient population at dispatch. This in turn may result in transportation delay. Moreover, the period before contact with EMCC is important and will not be directly affected by the prehospital CT strategy. Thus, it is crucial to increase public awareness of stroke symptoms.
Compared with conventional care of acute stroke, MSU care probably reduces the time from a patient’s first contact with the emergency dispatch center to thrombolysis, and increases the number of patients who receive thrombolysis. It may also lead to reduced time from a patient’s first contact with the emergency dispatch center to CT imaging, and to better functionality at 3 months after stroke (mRS score 0-3).
We found an absolute shortfall of 5.5 QALYs for ischemic stroke patients, and that the expected cost per QALY is about 385,000 Norwegian kroner or lower if one MSU successfully reaches at least 35-40% (145-171) of thrombolysis patients per year. Decision makers must consider whether they think it is plausible that a minimum of 35-40% of patients could receive the intervention.
Due to the lack of evidence, the effectiveness of decentralized CT stations outside hospitals and of prehospital CT in suspected severe head injuries is unknown.