TY - JOUR
T1 - Outcomes of clinical utility in amyloid-PET studies: state of art and future perspectives
AU - Cotta Ramusino, Matteo
AU - Perini, Giulia
AU - Altomare, Daniele
AU - Barbarino, Paola
AU - Weidner, Wendy
AU - Salvini Porro, Gabriella
AU - Barkhof, Frederik
AU - Rabinovici, Gil D.
AU - van der Flier, Wiesje M.
AU - Frisoni, Giovanni B.
AU - Garibotto, Valentina
AU - Teipel, Stefan
AU - Boccardi, Marina
N1 - Funding Information: V. Garibotto received financial support for research through her institution from Siemens Healthineers, GE Healthcare, Life Molecular Imaging, Cerveau Technologies, Roche, Merck. G.D. Rabinovici receives research support from the National Institutes of Health, Alzheimer’s Association, American College of Radiology, Rainwater Charitable Foundation, Gift from Edward and Pearl Fein, Avid Radiopharamaceuticals, Eli Lilly, Life Molecular Imaging, GE Healthcare. He has served as a consultant for Axon Neurosciences, Eisai, GE Healthcare, Merck, Genentech. He serves on a data safety monitoring board for Johnson & Johnson. He is an Associate Editor for JAMA Neurology. Funding Information: Open Access funding enabled and organized by Projekt DEAL. This study was supported by the Italian Ministry of Health (Ricerca Corrente 2020). V. Garibotto was also supported by the Swiss National Science Foundation (projects 320030_169876, 320030_185028 and IZSEZ0_188355) and by the Velux foundation (project 1123). F. Barkhof is the coordinator of AMYPAD, a project that received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115952. This Joint Undertaking receives the support from the European Union’s Horizon 2020 for research and innovation program and EFPIA. He is supported by the NIHR biomedical research center at UCLH. Research programs of Wiesje van der Flier have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. WF holds the Pasman chair. WF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, and WebMD Neurology (Medscape). WF is consultant to Oxford Health Policy Forum CIC and Roche BV. All funding is paid to her institution. WF is associate editor at Alzheimer’s, Research & Therapy. Funding Information: F. Barkhof is a member of steering committee and safety monitoring boards for Merck, Biogen and Bayer. He is a consultant for Novartis, Roche, IXICO, GeNeuro, and Combinostics; his institutions received research support from EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EPAD and AMYPAD consortia), Horizon (EuroPOND), UK MS Society, IMDI-NOW (PICTURE), NIHR UCLH Biomedical Research Centre, and ECTRIMS-MAGNIMS. He is section Editor for Neuroradiology. The other authors declare that they have no conflict of interest. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: To review how outcomes of clinical utility are operationalized in current amyloid-PET validation studies, to prepare for formal assessment of clinical utility of amyloid-PET-based diagnosis. Methods: Systematic review of amyloid-PET research studies published up to April 2020 that included outcomes of clinical utility. We extracted and analyzed (a) outcome categories, (b) their definition, and (c) their methods of assessment. Results: Thirty-two studies were eligible. (a) Outcome categories were clinician-centered (found in 25/32 studies, 78%), patient-/caregiver-centered (in 9/32 studies, 28%), and health economics-centered (5/32, 16%). (b) Definition: Outcomes were mainly defined by clinical researchers; only the ABIDE study expressly included stakeholders in group discussions. Clinician-centered outcomes mainly consisted of incremental diagnostic value (25/32, 78%) and change in patient management (17/32, 53%); patient-/caregiver-centered outcomes considered distress after amyloid-pet-based diagnosis disclosure (8/32, 25%), including quantified burden of procedure for patients’ outcomes (n = 8) (1/8, 12.5%), impact of disclosure of results (6/8, 75%), and psychological implications of biomarker-based diagnosis (75%); and health economics outcomes focused on costs to achieve a high-confidence etiological diagnosis (5/32, 16%) and impact on quality of life (1/32, 3%). (c) Assessment: all outcome categories were operationalized inconsistently across studies, employing 26 different tools without formal rationale for selection. Conclusion: Current studies validating amyloid-PET already assessed outcomes for clinical utility, although non-clinician-based outcomes were inconsistent. A wider participation of stakeholders may help produce a more thorough and systematic definition and assessment of outcomes of clinical utility and help collect evidence informing decisions on reimbursement of amyloid-PET.
AB - Purpose: To review how outcomes of clinical utility are operationalized in current amyloid-PET validation studies, to prepare for formal assessment of clinical utility of amyloid-PET-based diagnosis. Methods: Systematic review of amyloid-PET research studies published up to April 2020 that included outcomes of clinical utility. We extracted and analyzed (a) outcome categories, (b) their definition, and (c) their methods of assessment. Results: Thirty-two studies were eligible. (a) Outcome categories were clinician-centered (found in 25/32 studies, 78%), patient-/caregiver-centered (in 9/32 studies, 28%), and health economics-centered (5/32, 16%). (b) Definition: Outcomes were mainly defined by clinical researchers; only the ABIDE study expressly included stakeholders in group discussions. Clinician-centered outcomes mainly consisted of incremental diagnostic value (25/32, 78%) and change in patient management (17/32, 53%); patient-/caregiver-centered outcomes considered distress after amyloid-pet-based diagnosis disclosure (8/32, 25%), including quantified burden of procedure for patients’ outcomes (n = 8) (1/8, 12.5%), impact of disclosure of results (6/8, 75%), and psychological implications of biomarker-based diagnosis (75%); and health economics outcomes focused on costs to achieve a high-confidence etiological diagnosis (5/32, 16%) and impact on quality of life (1/32, 3%). (c) Assessment: all outcome categories were operationalized inconsistently across studies, employing 26 different tools without formal rationale for selection. Conclusion: Current studies validating amyloid-PET already assessed outcomes for clinical utility, although non-clinician-based outcomes were inconsistent. A wider participation of stakeholders may help produce a more thorough and systematic definition and assessment of outcomes of clinical utility and help collect evidence informing decisions on reimbursement of amyloid-PET.
KW - Alzheimer’s disease
KW - Amyloid-PET
KW - Clinical utility
KW - Diagnostic biomarkers
KW - Outcome
KW - Systematic review
UR - http://www.scopus.com/inward/record.url?scp=85100916722&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00259-020-05187-x
DO - https://doi.org/10.1007/s00259-020-05187-x
M3 - Review article
C2 - 33594474
SN - 1619-7070
VL - 48
SP - 2157
EP - 2168
JO - European journal of nuclear medicine and molecular imaging
JF - European journal of nuclear medicine and molecular imaging
IS - 7
ER -