Regarding quality assurance plans that address data validation and registry procedures, the current study is a single centre investigator-initiated study and therefore there are no plans for site monitoring and auditing. The reliability and validity of the MRI data has been previously confirmed with comparison to 3D histology data (Koppal et al. Quantitative fat and R2\* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis. Magn Reson Med. 2017;78(1):285-96.).
Concerning data checks, intraobserver reliability regarding baseline and follow-up measurements will be ascertained (Intraclass Correlation Coefficients (ICC), Bland Altman).
Data is collected from patient medical records (electronic), dedicated study record forms (paper) and clinical assessments, resulting in quantitative measures. These external data sources are transferred into a study database.
The current study is a clinical study, using only clinically validated laboratory parameters. The source of the lab values and their normal ranges is the electronic patient record. The normal ranges have been established by the clinical chemistry and haematology laboratories at Linköping University Hospital. Clinical diagnosis and procedures are recorded using the International Classification of Diseases (ICD) classification.
The study was approved by the Swedish Ethical Review Authority (approval nr: 2016-441-31) and performed in accordance with the Declaration of Helsinki. Written informed consent has been obtained from all study participants.
Patients are selected based on duplex ultrasound criteria established for the European Carotid Surgery Trial. A cut-off at doppler flow velocity has been used to identify eligible patients and after considering inclusion and exclusion criteria patients have been contacted by the study clinicians dr Elin Good or dr Ebo de Muinck for recruitment. Any registration for adverse events follows the same procedures as in routine care.
Sample size assessment was based on results from previous studies in relation to our primary outcome variables. For example, one study with 24 patients and a follow-up time of three months experienced a significant reduction of lipid rich necrotic core, using magnetic resonance imaging (Alkhalil et al. T2 mapping MRI technique quantifies carotid plaque lipid, and its depletion after statin initiation, following acute myocardial infarction. Atherosclerosis. 2018;279:100-6.). Therefore, we aimed to include 50 patients who have completed both baseline and follow-up, and the follow-up time was set to 12 months.
Our plan for missing data in situations where variables are missing, unavailable, non-reported, uninterpretable etc is to not exclude the study participant, in order to avoid bias. For example, in cases where the imaging data from one patient is lost, we will still use the remaining clinical data from that patient if the patient has been included in the study.
Regarding Statistical analysis, SPSS Statistics 26 (International Business Machines Corporation, New York, NY, USA) is used for statistical analysis. Continuous variables are summarized as mean ± standard deviation (SD). To address the primary objectives (the strength of the association between fat fraction (FF) and R2\*) Pearson correlation coefficient is used, and Paired-samples T test is used for analysing changes in quantitative values between baseline and follow-up.
Intra-observer repeatability measurements were calculated using ICC. For ICC evaluation we used two-way random effect models, checking for absolute agreement, average measures presented.
