Real-world Independent Testing of e-ASPECTS Software (RITeS): statistical analysis plan

Background: Artificial intelligence-based software may automatically detect ischaemic stroke lesions and provide an Alberta Stroke Program Early CT score (ASPECTS) on CT, and identify arterial occlusion and provide a collateral score on CTA. Large-scale independent testing will inform clinical use, but is lacking. We aim to test e-ASPECTS and e-CTA (Brainomix, Oxford UK) using CT scans obtained from a range of clinical studies. Methods: Using prospectively collected baseline CT and CTA scans from 10 national/international clinical stroke trials or registries (total >6600 patients), we will select a large clinically representative sample for testing e-ASPECTS and e-CTA compared to previously acquired independent expert human interpretation (reference standard). Our primary aims are to test agreement between software-derived and masked human expert ASPECTS, and the diagnostic accuracy of e-ASPECTS for identifying all causes of stroke symptoms using follow-up imaging and final clinical opinion as diagnostic ground truth. Our secondary aims are to test when and why e-ASPECTS is more or less accurate, or succeeds/fails to produce results, agreement between e-CTA and human expert CTA interpretation, and repeatability of e-ASPECTS/e-CTA results. All testing will be conducted on an intention-to-analyse basis. We will assess agreement between software and expert-human ratings and test the diagnostic accuracy of software. Conclusions: RITeS will provide comprehensive, robust and representative testing of e-ASPECTS and e-CTA against the current gold-standard, expert-human interpretation.