IMAGING IN ALZHEIMER'S DISEASE TRIALS: IMPACT ON PATIENT RECRUITMENT, RETENTION AND LOGISTICS

Abstract

MRI and PET is now extensively utilized in AD trials for patient eligibility, efficacy assessment efficacy, and safety evaluations. Standardization of MRI and PET methodology across the sites is essential to acquire consistent data. This requires prospective site qualification, evaluation of phantom data, training and continuous monitoring. Phantom imaging and standardization is especially important for estimation of brain volumes and PET data. Patient Eligibility: Many neurological diseases like vascular dementia, multiple sclerosis, vascular pathology, neoplasms have similar presentation as AD or could confound the assessment of drug therapy. Inclusion of wrong patients has ethical and legal issues and data could be excluded from the analysis. Eligibility evaluation and optimization of eligibility read process will be discussed. Evaluation of Amyloid Related Imaging Abnormalities (ARIA): ARIA were observed in amyloid-β trials. MRI findings of ARIA include vasogenic edema (ARIA E), micro and macro hemorrhages (ARIA H) and superficial siderosis. FDA had mandated frequent MRIs in all AD trials putting burden on sites and patients. Our experience in ARIA evaluations in large phase III study at >350 sites will be presented. new guidance will also be discussed Efficacy evaluation: MRI is utilized to evaluate various volumes of brain. FDG PET has been used to measure metabolic activity of brain. We will share our experience about site and central independent reads. MRI and PET are used for patient eligibility, efficacy and safety assessments. Imaging must be prospectively planned including standardizing imaging methodologies, site selection process and selecting eligibility and efficacy criteria. Training should be transparently conducted and documented.