TIME FOR A CORE OUTCOMES SET? A FOCUS ONDISEASE MODIFYING THERAPIES FOR EARLY ALZHEIMER'S DISEASE
Author(s)
Heather Eames, BSc, MSc, PharmD1, Cliona A. Flynn, BSc, MSc2, Sinead O'Neill, BSc, MSc, PhD3, Marie Harte, BSc, MSc3, Caitriona Ni Choitir, BSc, MSc4, Sean Kennelly, MD5, Roisin Adams, BSc, PhD3, Laura Mccullagh, BSc, PhD6.
1Health Technology Assessor, NUIG, Ireland, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Newry, United Kingdom, 3National Centre for Pharmacoeconomics, Dublin, Ireland, 4national centre for Pharmacoeconomics, dublin, Ireland, 5Tallaght University Hospital, Dublin, Ireland, 6National Centre for Pharmacoeconomics, Dublin 8, Ireland.
1Health Technology Assessor, NUIG, Ireland, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Newry, United Kingdom, 3National Centre for Pharmacoeconomics, Dublin, Ireland, 4national centre for Pharmacoeconomics, dublin, Ireland, 5Tallaght University Hospital, Dublin, Ireland, 6National Centre for Pharmacoeconomics, Dublin 8, Ireland.
OBJECTIVES: The first disease-modifying therapies for early Alzheimer’s Disease (AD-DMTs) have been licensed by the European Medicines Agency (EMA), with several others in the development pipeline. The EMA recommends that efficacy of AD-DMTs is assessed across global, cognitive, and functional outcomes, but is not prescriptive regarding which outcomes are used. This study examined the heterogeneity of outcomes used across randomised controlled trials (RCTs) of AD-DMTs.
METHODS: A Systematic Literature Review was conducted, from inception to January 2026 for RCTs of AD-DMTs (that had been identified by the author via horizon scanning). The population were those with early Alzheimer's Disease, defined as per international guidelines and presence of a positive AD biomarker. Data extracted included population characteristics, outcome definition and RCT duration.
RESULTS: Of 2,851 records identified, 15 studies reporting on 10 RCTs investigating 7 AD-DMTs versus placebo, were identified. Across the 10 RCTs, Cognitive endpoints included; the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (n=7), across three subscales, and the Mini-Mental State Examination (n=3). Functional endpoints included; Alzheimer’s Disease Cooperative Study - Instrumental Activities of Daily Living (n=2), Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment (n=1), and Alzheimer's Disease Cooperative Study - Activities of Daily Living (n=3). Global endpoints included; Clinical Dementia Rating - Sum of Boxes (n=8), Integrated Alzheimer's Disease Rating Scale (n=2), and Alzheimer's Disease Composite Score (n=2). Timing of outcome measurement was variable across the RCTs, ranging from 46 to 78 weeks.
CONCLUSIONS: Despite measurement of the same underlying outcomes, heterogeneity was evident across outcomes reported in RCTs for AD-DMTs. Strategies, such as core outcomes sets, may reduce heterogeneity and promote development of high-quality evidence to support decision making. Generally, it is inappropriate to compare RCTs of different durations. Providing recommended intervals for outcome assessment may permit comparability of outcomes from RCTs of different durations.
METHODS: A Systematic Literature Review was conducted, from inception to January 2026 for RCTs of AD-DMTs (that had been identified by the author via horizon scanning). The population were those with early Alzheimer's Disease, defined as per international guidelines and presence of a positive AD biomarker. Data extracted included population characteristics, outcome definition and RCT duration.
RESULTS: Of 2,851 records identified, 15 studies reporting on 10 RCTs investigating 7 AD-DMTs versus placebo, were identified. Across the 10 RCTs, Cognitive endpoints included; the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (n=7), across three subscales, and the Mini-Mental State Examination (n=3). Functional endpoints included; Alzheimer’s Disease Cooperative Study - Instrumental Activities of Daily Living (n=2), Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment (n=1), and Alzheimer's Disease Cooperative Study - Activities of Daily Living (n=3). Global endpoints included; Clinical Dementia Rating - Sum of Boxes (n=8), Integrated Alzheimer's Disease Rating Scale (n=2), and Alzheimer's Disease Composite Score (n=2). Timing of outcome measurement was variable across the RCTs, ranging from 46 to 78 weeks.
CONCLUSIONS: Despite measurement of the same underlying outcomes, heterogeneity was evident across outcomes reported in RCTs for AD-DMTs. Strategies, such as core outcomes sets, may reduce heterogeneity and promote development of high-quality evidence to support decision making. Generally, it is inappropriate to compare RCTs of different durations. Providing recommended intervals for outcome assessment may permit comparability of outcomes from RCTs of different durations.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA88
Topic
Clinical Outcomes, Health Technology Assessment
Disease
Neurological Disorders