Title: A UK multicentre long term longitudinal study of unruptured intracranial aneurysms: the Risk of Aneurysm Rupture (ROAR) Study
Funder: Department of Health and Social Care

Abstract: Background Unruptured intracranial aneurysms are found in 3% of the adult population and have the potential to rupture causing subarachnoid haemorrhage. Subarachnoid haemorrhage has a mortality rate of 30% and there are high rates of disability and cognitive problems amongst survivors. Microsurgical and endovascular treatments exist to occlude UIA and can prevent them from rupturing in the future. However, these treatments carry a risk of complications including stroke and death. Therefore, a patient s UIA needs to carry sufficient risk of rupture to justify treatment. Unfortunately, our understanding of the risk of UIA rupture is poor. It is based on a small number of natural history studies, each with inherent biases or confounders, and significantly different findings, which have been combined into the PHASES score. Despite its obvious limitations, the PHASES score is the best available tool and is widely used by neurosurgeons. However, it has never been externally validated, uses limited predictors, and is based largely on short (1 year) periods of follow up. Aims The ROAR study aims to 1) validate the PHASES score in a UK population, 2) build a further model including all commonly available predictors, and 3) determine if rupture risk is linear or changes over time. Methods The ROAR study will generate a national cohort of patients with UIA through retrospective patient identification of individual neurosurgical units for patients diagnosed between 1/1/2006-31/12/2020. The patients will undergo eligibility screening and baseline aneurysm and clinical data collection. Follow up will be conducted by searching all patients against national hospital admission databases for England, Wales and Scotland (HES, PEDW, SMR) to identify admissions for subsequent SAH, or other types of intracranial haemorrhage. Death registers linked to these databases will also be searched. All admissions identified will then be checked against the original diagnostic imaging to confirm the diagnosis. Timeline Study site set up, patient identification and baseline data collection is expected to take 13 months starting in July 2022. This will culminate in submitting the patient cohort to the national admission databases. Analysis of data and manuscript preparation will take a further 12 months with the final results available in July 2024. Anticipated impact and dissemination This study will immediately impact the care of almost all of the 3% of people with aneurysms in whom management decisions are based solely on the perceived risk of rupture. The study will be an order of magnitude larger than any previous similar study and therefore provide the most accurate and personalised estimates of lifetime risk which are desired by patients. The results will be disseminated to clinicians through conference presentations and peer reviewed journals. Patients will be made aware of the results through support groups, charities, social media and the study website. The study will also produce a patient specific online calculator which can be used by both patients and clinicians to estimate rupture rates for specific patients and their aneurysms. This calculator will allow patients to better understand their risks and need for treatment or follow up imaging.

Lay abstract: An aneurysm is a bulge in a blood vessel due to a weakness in its wall. They are common and 3% of people have them in the brain. They can burst and cause bleeding which frequently leaves people dead or disabled. Bleeding can be prevented by procedures to treat the aneurysm. However, these procedures can cause serious complications such as stroke. They should therefore only be performed in patients whose risk of bleeding is higher than the risk of complications from the procedures. The problem is that we are not sure exactly what the risk of bleeding from an aneurysm is. Our best estimates come from the previously published PHASES study. This proposed a score based on 6 items, like patient age and aneurysm size, to estimate the risk of a brain aneurysm bleeding over the next 5 years. However, the PHASES score has several design flaws and neurosurgeons are unsure how accurate it is. For example, 4 out of 5 patients in the study were either Finnish or Japanese, who are the two populations in the world believed to have a higher risk of rupture than other populations. It is therefore not possible to be sure if this applies to patients in the UK. This is a real problem for patients who have to make the difficult decision whether to undergo high risk procedures for their aneurysm or live with their aneurysm not knowing the risk they are taking. This is regularly cited as the greatest concern of patients with unruptured aneurysms and our involvement with the Wessex subarachnoid haemorrhage patient support group reports this is their top priority for future research. We therefore want to study a large number of patients with aneurysms that have not burst (and are neither Finnish nor Japanese), to see which ones go on to burst and bleed. We will identify patients from neurosurgical units throughout the UK and record details, such as the aneurysm size, from local hospital records. However, subsequent bleeds from their aneurysm could occur elsewhere in the country therefore we will use national databases which record admissions to any hospital (and all deaths) to see which aneurysms went on to bleed. The main aim of the study is to determine whether or not the PHASES score is accurate in a UK population and, refine the score to increase its accuracy for predicting rupture risk. This will be of huge benefit by aiding decision making for patients with aneurysms and protect them from the harm of over- or under-treatment of an aneurysm. The results will be disseminated by presentation at stroke and neurosurgery conferences and publication in peer-reviewed journals with immediate impact on patient care.

Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CARDIOVASCULAR;STROKE