ABSTRACT
Nearly 7 million people in the United States are living with Alzheimer’s disease (AD). As people with AD progress
through the stages of this disease, their ability to function independently and carry out activities of daily living
(e.g., household chores and personal care) decreases due to cognitive impairment progressing to dementia,
leading to increased burden on caregivers and the US healthcare system. However, a psychometrically sound,
publicly available measure of cognition-dependent day-to-day functioning for persons with AD has not been
recognized by FDA as fit-for-purpose for use in early-stage AD drug development. We propose the preparation
and submission of a Qualification Plan (QP) to support the qualification of the Virtual Reality Functional Capacity
Assessment Tool-Short List (VRFCAT-SLx) as a performance outcome (PerfO) measure of cognition-dependent
day-to-day functioning in people diagnosed with biomarker-positive, clinical stages 2 and 3 AD.
A measure of day-to-day functioning was accepted into the Center for Drug Evaluation and Research’s (CDER’s)
Clinical Outcome Assessment (COA) Qualification Program under DDT #000004 on October 12, 2016. The PRO
Consortium’s Cognition Working Group selected the VRFCAT-SLx as the measure for qualification as it has has
qualitative evidence supporting its content validity. A confirmatory qualitative study is underway in people with
biomarker-positive, clinical stages 2 and 3 AD. Next, a quantitative evidence strategy will be prepared, supported
by a study protocol and statistical analysis plan (SAP) used to develop a Qualification Plan (QP). The next step
in the qualification process will be submission of the QP to FDA to support qualification of the VRFCAT-SLx for
use in AD drug development.
Our approach includes 4 aims. For Aim 1, we will convene an advisory panel of clinicians and patient participants
to provide recommendations on study design to increase the feasibility of our proposed strategy and to review
the study protocol and other study documents. For Aim 2, we will prepare a description of the proposed
quantitative evidence generation strategy (including development of a protocol and SAP) designed to assess the
VRFCAT-SLx’s measurement properties. For Aim 3, we will develop the QP by compiling the evidence from
literature and qualitative data from two cognitive interview studies and using the protocol and SAP to complete
the relevant sections of the QP, following FDA’s COA QP content outline. Aim 4 will involve compiling and
submitting the QP with all necessary appendices and attachments. The goal of this project will be a publicly
available PerfO measure for assessing cognition-dependent day-to-day functioning in clinical trials for people
with biomarker-positive, clinical stage 2 and 3 AD. Qualifying the VRFCAT-SLx will fill a critical gap in the
measurement of day-to-day functioning in AD treatment trials.
