Artificial intelligence (AI)-derived software to help clinical decision making in stroke

No published evidence was found for 9 of the 13 technologies in the assessment

3.6 The committee considered the available evidence for each technology and indication. It noted that the external assessment group's (EAG's) review found no published evidence that met review inclusion criteria for Accipio, Aidoc, Biomind, Brainscan CT, Cercare (Perfusion), CT Perfusion 4D, icobrain ct, Neuro Solution or qER for the indications in the assessment. An updated review done by the EAG for the third committee meeting in August 2023 also found no further studies that met the review inclusion criteria for these technologies. So, the committee was unable to consider these technologies further as part of its discussions and recommended more research. Only 1 study was identified that assessed the CINA head software, and this only reported accuracy data for the technology used as a standalone intervention and not alongside clinician interpretation (as it is intended to be used). There were more studies, including some reporting outcomes such as the impact of software on treatment (see sections 3.9 and 3.10) for the remaining 3 technologies (e-Stroke, RapidAI and Viz).

Impact of the AI-derived software's analytical functions on a healthcare professional's ability to identify people for treatment is uncertain

3.7 The EAG's initial review found 15 diagnostic accuracy studies but these all evaluated the performance of the AI-derived software as a standalone intervention and not alongside clinician interpretation (as it is intended to be used). Also, the risk of bias because of patient selection in many studies was high, particularly when they used a case-control study design, or unclear because of inadequate reporting. The reference standard used in the studies ranged from review by a single clinician to a panel of clinicians with or without access to clinical data alongside images. But, it was often unclear whether these clinicians were blinded to the output from the AI software and difficult to determine if they were likely to correctly classify the target condition because their experience was not clearly reported. So, because the studies were not generalisable to how the technologies would be used in practice, limited conclusions could be made about the accuracy of the technologies. Also, the committee noted that none of the studies separately reported accuracy for people aged over 80 with cerebrovascular disease, when the interpretation of scans is often more challenging. An updated review done by the EAG for the third committee meeting in August 2023 also found no studies that compared the performance of a healthcare professional reviewing scans, with and without use of the software, that met review inclusion criteria. The committee concluded that the impact of the analytical functions of the AI-derived software on a healthcare professional's ability to identify people for whom treatments like thrombolysis and thrombectomy are suitable is uncertain.

It is difficult to draw conclusions on the reported comparative accuracy data

3.8 The committee recognised that 1 study (Seker et al. 2020), relevant to guiding mechanical thrombectomy decisions for people with an ischaemic stroke using CT angiography, reported some comparative accuracy data. It reported data both on the accuracy of e-CTA software (Brainomix) alone and for scan reviews done by clinicians of varying experience alone compared with a common reference standard. This was an experienced neuroradiologist who had access to both imaging and clinical data. This is important because the usefulness of AI-software-assisted scan review may vary between centres with differing levels of stroke specialism, and between different types of clinicians (for example, doctors in hospital emergency departments, stroke specialists, radiologists and neuroradiologists). But the committee noted that it is difficult to draw conclusions from the study on how the software would perform when used alongside clinician review because it did not provide information on whether clinicians and the software missed the same or different cases.

It is uncertain whether using AI-derived software to help guide treatment decisions in stroke leads to faster access to treatment

3.9 In the EAG's initial review there were 7 observational studies that compared time to treatment before and after implementing AI-derived software in clinical practice, assessing e-Stroke, RapidAI and Viz. Most of the studies suggested that time to treatment for people who had thrombectomy or thrombolysis had reduced after implementing the software. The EAG reported that there was a high risk of bias in these studies because of the limited information they included. The studies were all retrospective, study populations and stroke care settings were not clearly described, the point in the care pathway when the software was used and by whom was often unclear. Also, it was unclear if the before and after populations had similar characteristics, and whether adding the software was the only change to the care pathway. Because only people with a positive scan result were included in the studies, it is unclear whether people with a false negative result would experience a delay in treatment. An updated review done by the EAG for the third committee meeting in August 2023 identified further studies (using e-Stroke and Viz) that assessed the impact of test use on time to treatment. Studies done in centres that needed to transfer people to have a thrombectomy reported reductions in time to thrombectomy, although the EAG highlighted concern about study quality, including the same issues highlighted in the original report. The EAG noted that the UK implementation report (an interim report of an ongoing study by an Academic Health Science Network) did not collect data on the effects on time to treatment for centres that needed to transfer people for thrombectomy. The committee recalled that the image sharing function of the technologies may be a driving factor in improving time to treatment (see section 3.4) but that other changes to stroke care may also be factors (see section 3.3). It concluded that it is uncertain whether using AI-derived software to help guide treatment decisions in stroke leads to faster access to thrombolysis or thrombectomy.

It is uncertain whether using AI-derived software leads to increases in the number of people having a thrombectomy

3.10 An updated review done by the EAG for the third committee meeting in August 2023 identified 2 studies that assessed impact of e-Stroke on the numbers of thrombectomies done. Both showed increases in the proportion of people who had a stroke having a thrombectomy after implementation of e-Stroke. The EAG stated that neither study provided sufficient information to establish that populations were comparable before and after the implementation of the software, and that this was the only change to the care pathway. It further highlighted that 1 study (an interim report provided by an Academic Health Science Network of an ongoing UK implementation study) was done during the COVID-19 pandemic and it was unclear how rates of CTA scanning and thrombectomy may have been affected by this. The AHSN work reported that the proportion of people having thrombectomy who had presented more than 6 hours after the onset of symptoms increased significantly after implementation of e-Stroke. The committee noted that study authors suggested that this may be because e-Stroke's rapid image sharing functionality allows quicker access to thrombectomy specialists, and helps their decision making. This could make it less likely they will decline a transfer for a patient who was last well more than 6 hours ago if they can review their CT scans. Experts highlighted that a NICE recommendation about offering thrombectomy for people between 6 hours and 24 hours of symptom onset (including wake‑up strokes) included the need to establish the potential to salvage brain tissue, as shown by imaging such as CT perfusion (CTP) showing limited infarct core volume. They further highlighted that RapidAI software had been used to analyse CTP scans in identifying people eligible for studies underpinning this recommendation. Experts disagreed about the extent that analysis from the AI-derived software of CTP scans adds to information routinely available from CT scanners and would be needed in practice for thrombectomy to be available for this later presenting group. Experts further highlighted that the National Optimal Stroke Imaging Pathway includes doing CTP scans at the same sitting as plain CT head and CTA, and that CTP scans are increasingly available at acute stroke centres. But such centres have less expertise to interpret these scans and would benefit from rapid support from comprehensive stroke centre teams. The EAG highlighted that there is little data on technology performance when assessing CTP scans. In the AHSN work, this function of the e-Stroke package was only available in comprehensive stroke centres and the extent it was used was uncertain.

It is unclear whether using AI-derived software to help guide treatment decisions in stroke leads to better clinical outcomes

3.11 The committee noted that the studies that compared time to treatment before and after implementing AI-derived software provided limited information on how it affected clinical outcomes. In particular, there was no information on clinical outcomes when the software was used for guiding thrombolysis treatment decisions for people with suspected acute stroke using a non-enhanced CT scan. Six studies, in which the software was used for guiding mechanical thrombectomy using CT angiography or CT perfusion brain scans, reported on the proportion of people who were functionally more independent (with modified Rankin Scale [mRS] score 2 or less), length of hospital stay, mean 90-day mRS score and rate of complications and death during hospital stay after software implementation. The committee noted that the results from these studies were conflicting, with some reporting a positive and others a negative impact. The EAG advised that the studies were unlikely to have been appropriately set up to adequately capture any differences in clinical outcomes. So, the reported data is unlikely to show the true effects of implementing the technologies. The EAG also highlighted that the evidence described outcomes only for people who had a thrombectomy. Clinical experts explained that while using AI-derived software could help improve outcomes for people who are offered treatment if they have it sooner, it could also worsen outcomes for people who were not offered treatment or who had incorrect treatment if their diagnosis was missed because of the influence of the software on clinical decision making. An updated review done by the EAG for the third committee meeting in August 2023 identified further studies that assessed the software's impact on mRS and mortality. Results were mixed, in terms of indicating possible benefit or detriment, and the 1 study that had longer follow up (6 months) had very high levels of missing data.

More information about the reliability of AI-derived software to help guide treatment decisions in stroke is needed

3.12 Only 1 published study (Kauw et al. 2020) reported on the technical failure rate of AI-derived software. This study reported that the software failed to process CT perfusion brain scan data and return results to assist the review of 20 of the 176 scans (11%) included in the analysis. Causes for failures were severe motion, streak artifact and poor arrival of contrast. The clinical experts advised that it is possible that the failure in clinical practice may be even higher. The patient expert raised concerns that technical failures could result delays in diagnosis and access to time-sensitive treatments. The committee concluded that the reliability of AI-derived software to help guide treatment decisions in stroke in clinical practice is not clear. It recommended further research to measure technical failure rates of AI-derived software used to help guide treatment decisions in stroke. Information about the reasons for test failures should be recorded.

There was not enough clinical evidence to evaluate the cost effectiveness of AI-derived software in 2 of the 3 assessed indications

3.13 Evidence on using AI-derived software for guiding thrombolysis treatment decisions for people with suspected acute stroke using a non-enhanced CT scan, and mechanical thrombectomy treatment decisions for people with ischaemic stroke using CT perfusion after a CT angiography brain scan, was very limited. In particular, there was no evidence on the diagnostic accuracy of the technologies when used alongside clinician interpretation or how they might perform relative to clinician alone in either indication (see section 3.7). No clinical outcomes were reported for using AI-derived software to guide thrombolysis treatment decisions for people with suspected acute stroke (see section 3.11). So, the EAG did not build health economic models to evaluate the cost effectiveness of the software in these 2 indications. The committee concluded that it would be useful to understand the cost effectiveness of the AI-derived software in these indications but accepted that there is currently not enough data available to inform modelling.

Accuracy estimates in the model for using AI-derived software in thrombectomy decisions may not reflect the accuracy seen in clinical practice

3.14 The EAG explained that because there was more data related to using AI-derived software for guiding mechanical thrombectomy decisions for people with ischaemic stroke using CT angiography than for the other 2 indications, it could build an exploratory economic model for this. Because no diagnostic accuracy data was available for using the technologies as intended (see section 3.7), the EAG elicited accuracy estimates for the model from clinical experts. These estimates were sought for a hypothetical average AI-derived software when used alongside clinician interpretation and for the comparator in the model, clinician interpretation alone. The committee noted that it is challenging for people to estimate something like accuracy that they cannot directly see. The committee concluded that while expert elicitation is an appropriate method to obtain model inputs when data is scarce, it is uncertain if the accuracy estimates in the model reflect the accuracy of the AI-derived software that would be seen in clinical practice.

Health-related quality of life, given the exploratory nature of the model, is adequately captured

3.15 The committee considered whether the model captured the effect that having a stroke has on people's quality of life. The EAG explained that the utility values for health-related quality of life used in the base case were linked to the mRS health states, from Rivero-Arias et al. (2010). This study used mRS and EQ-5D-3L information that was collected from people with stroke or transient ischaemic attack who took part in the Oxford Vascular Study (OXVASC) in the UK. The committee concluded that the health-related quality of life, given the exploratory nature of the model, was adequately captured. But, it recalled how important quality of life is to people who survive stroke (see section 3.1) and that further research on the impact of the AI-derived software on quality of life after stroke using EQ-5D would be beneficial (see section 3.22). It further considered that better understanding of health-related quality of life after stroke, for example aspects such as cognitive or emotional difficulties and fatigue that are important to people who survive stroke, would be helpful. It noted that the research priorities from the Stroke Priority Setting Partnership (led by the Stroke Association with the James Lind Alliance) and research needs from the National Stroke Programme (NHS Accelerated Access Collaborative) include understanding and managing emotional and psychological effects of stroke that may be less visible.

Small increases in the number of thrombectomies done in the EAG's model are enough for the test to be cost effective

3.16 In the EAG's model, the increase in the number of people having thrombectomies if the software is used does not need to be large for it to be cost effective. This includes if specificity is worse with the addition of AI-derived software to healthcare professional review (that is, there are more false positive results), based on a study identified by the EAG (Andralojc et el. 2023). The committee noted at the third committee meeting there was now some evidence that the technologies increase the number of people having thrombectomy but recalled that this was uncertain (see section 3.10). The EAG commented that if using the technologies means different people are identified for thrombectomy this could impact on how effective it is. That is, the relative effectiveness of thrombectomy in the additional people that get it, would be equal to the effectiveness of thrombectomy for people that already get it (without the addition of the software). Experts acknowledged this but commented that studies routinely show benefits from increased thrombectomy use.

Further evidence on test performance is important alongside data on impact on time to, or occurrence of, treatment

3.17 The EAG's model included additional cost impact for false positive results (for ambulance transfer and time on a stroke unit). Experts agreed that such cases would be detected before having an unnecessary thrombectomy, but also highlighted that time spent reviewing these scans increases the work pressures on healthcare professionals. The EAG highlighted uncertainty in how software use will affect numbers of false positive results, and that this will impact cost effectiveness. The impact of false negative cases (people with eligible large vessel occlusions [LVOs] who do not have thrombectomy) was included in the model. Experts commented that such cases would likely eventually be detected, for example if ongoing symptoms suggested an issue. But this could mean delays to treatment (increased time to thrombectomy), which may impact eligibility for treatment (numbers having thrombectomy). Data on the impact of AI-derived software on the performance of healthcare professionals to identify people for whom thrombolysis or thrombectomy is suitable would help assess this. The EAG stated that data on time to treatment alone is insufficient to assess cost effectiveness, because the technologies can affect who has treatment, as well as how fast this is done. The committee agreed that further data on the impact of the addition of AI-derived software on the performance of healthcare professionals to identify people eligible for thrombolysis or thrombectomy is important to generate, alongside data on time to treatment and how many people have treatment.

Cost effectiveness of AI-derived software is uncertain, but it is plausible they are cost effective

3.18 The committee considered whether it was possible to determine the cost effectiveness of AI-derived software for guiding mechanical thrombectomy decisions for people with an ischaemic stroke using CT angiography from the EAG's model. It recalled that the model was built using diagnostic accuracy estimates elicited from experts (see section 3.14). This meant that the model did not reflect any of the individual software but modelled a hypothetical average AI-derived software. The committee noted that in reality, the different technologies may perform differently from this modelled average technology but acknowledged that there was no evidence on their performance when used as intended (see section 3.7). The committee concluded that cost effectiveness of AI-derived software for guiding mechanical thrombectomy decisions for people with an ischaemic stroke using CT angiography is uncertain. But it recalled that small increases in the number of people having thrombectomy caused by AI-derived software use in the EAG's model probably would be enough for the technologies to be cost effective, and there was at least some data to suggest this may occur (see sections 3.10 and 3.16). The committee concluded that while cost effectiveness is uncertain, the technologies could potentially be cost effective. But further data is needed to confirm this.

Some technologies can be used in the NHS while further evidence is generated

3.19 Further evidence is needed to better estimate the cost effectiveness of the technologies, so the committee did not recommend routine use in the NHS. It recalled that the technologies are already widely in use (see section 3.3). Experts at the third committee meeting highlighted benefits they are seeing from the technologies, and the committee considered that it was not appropriate to recommend stopping use. There was more data for 3 of the technologies (e-Stroke, RapidAI and Viz), including impact on time to treatment and how many people get treatment. The committee recalled there was uncertainty about how using the technologies impacted a healthcare professional's ability to identify people for thrombolysis or thrombectomy. But it concluded that, as long as these technologies were only used alongside clinician decision making (see section 3.5), they could be used in the NHS while further evidence is generated. The remaining technologies should only be in research. Because the image sharing function of the technologies is likely to be a large part of their value (see section 3.4), it is important that centres using the technologies ensure that the images that are shared can be remotely reviewed to help with decision making by healthcare professionals at a different site.

Ongoing use in the NHS and data collection

3.20 The EAG commented that the widespread use of these technologies in the NHS in England limits the potential for commissioning some types of high-quality primary research. It suggested that retrospective re-analyses of stored radiology reports, collected during the implementation of these technologies, may have potential to inform estimates of the accuracy of AI-derived software technologies in combination with clinical judgement. Committee members also highlighted the potential use of retrospective data to help answer outstanding evidence issues, potentially making use of data routinely collected in the NHS, such as the Sentinel Stroke National Audit Programme (SSNAP). The committee were aware that data collection as part of the AHSN's work is ongoing and full analyses are yet to be completed, which may provide useful further evidence.

Data should be collected from a representative population and reflect how the software may add benefit to the NHS

3.21 The EAG highlighted that it was not clear from available data whether the populations assessed were representative of the UK stroke population in terms of age, comorbidities and family background. The committee emphasised that further data collection should be done in populations that represent people having treatment in the NHS, including assessing factors that could impact on technology effectiveness such as age, sex, ethnicity, socioeconomic status and comorbidities. The committee also recalled that people presenting longer after onset of symptoms may be in particular need of greater access to treatment (see section 3.1) and encouraged this group to be included in further evidence generation. The committee recalled that the most benefit of the technologies may be for people presenting to sites that cannot do thrombectomies (and so a transfer is needed for this). Data collection should reflect this, for example by assessing the impact of software on the performance of clinicians working in acute rather than comprehensive stroke centres. Ideally studies should describe the level of experience of the clinicians interpreting the CT brain scans and include both people who had and did not have a particular type of treatment. Studies should also consider reporting data separately in subgroups when using the technologies may be particularly useful or less effective (for example in older people, particularly those aged over 80, with small vessel disease and calcification of the cerebrovasculature, people with an unknown time of stroke onset or wake-up stroke and people who have had a previous stroke).

Data on clinical outcomes would be beneficial

3.22 Both the EAG's model and previous assessments of tests related to stroke done for NICE diagnostic assessment programme guidance have used a linked evidence approach to estimate the impact of test use on clinical outcomes like mRS, rather than needing direct evidence of this. The committee also noted that in the EAG's model only very small improvements in mRS are needed for the technologies to be cost effective. Direct data on the impact of AI-derived technology use on clinical outcomes like mRS or mortality would be beneficial for this assessment but not essential.