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The Virtual Reality Functional Capacity Assessment Tool (VRFCAT): Data in Support of an Accepted Application for the FDA Clinical Outcome Assessment Qualification ProgramWilliam P Horan1, Alexandra S Atkins1, Luca Pani1,2, Philip D Harvey1,2, Tim Clayton1, Caren Gadigian1, Shane Baldwin1, Richard SE Keefe1,3 1 VeraSci (Durham, NC), 2 University of Miami (Miami, FL), 3 Duke University (Durham, NC)
BACKGROUNDThe FDA has guided drug developers focused on cognitive improvement to demonstrate not only basic improvement on cognitive endpoints, but also improvement on a co-primary measure of functional capacity.
The Virtual Reality Functional Capacity Assessment Tool (VRFCAT©) is a computer based virtual-reality measure of functional capacity. As shown below, the VRFCAT uses a realistic simulated environment to recreate routine activities of daily living.
Our application for the VRFCAT has officially been accepted into the FDA’s Clinical Outcome Assessment (COA) Qualification Program. This program is intended to qualify drug development tools that can be relied on to have a specific interpretation and application in any drug development program and regulatory review.
The FDA accepted the VRFCAT application into the COA Qualification Program after reviewing the development process and extensive quantitative evidence supporting its clinical trial utility, which is summarized in the accompanying wheel and spokes diagram
VRFCAT SCREENSHOTS AND 12 TASKS:Kitchen Bus Stop Grocery Store
Pick up the recipe on the counter Search for ingredients in cabinets and refrigerator Cross off the ingredients that you already have, pick up the bus schedule from the counter; Pick up the billfold on the counter; Exit the apartment and head to the bus stop
3
4
5
2
1
Apartment: Wait for the correct bus to the grocery store and board it when it arrivesAdd the exact bus fare and pay for the bus
7
6
Bus to store: Select a food aisle to begin shoppingContinue shopping for the necessary ingredients, and check out when finishedAdd up the exact amount for your purchase and pay for groceries
9
10
8
Store:
Spoke I
Spoke IISpoke IIISpoke
IVSp
oke V
Conceptof Interest
=Claim
VRFCAT modified and refined through a rigorous scale development processAn initial tutorial was added to facilitate subject comprehension and comfort with technologyTranslated and culturally adapted versions have been tested in 6 languagesValidation studies for new COU’s (MDD, MCI, PD, MS) are underway
V. Modify Instrument
Strong test-retest reliability and minimal practice effectsSensitive to treatment with social cognitive training in schizophrenia
IV. Longitudinal Evaluation of Measurement Properties
The VRFCAT was initially drafted based on extensive literature review and expert inputIt has been refined through an iterative, multi-stage process
II. Draft Instrument and Evaluate Content Validity
Strong discrimination of patients from healthy controls, psychometrics, and convergent validityFormal manual available
III. Cross-sectional Evaluation of Other Measurement Properties
COU: Clinically stable schizophrenia patients COI: Functional capacity, which refers to an individual’s capacity for performing key tasks of daily living
I. Identify Context of Use (COU) and Concept of Interest (COI)
www.VeraSci.com • 919.401.4642 • [email protected] • 3211 Shannon Rd, Suite 300 Durham, NC 27707 USA
NEXT STEPSWe received a grant from the FDA to collect qualitative evidence to confirm the content validity of the VRFCAT. We will conduct semi-structured interviews with patients, family members, and peer support specialists to determine whether they view the skills measured by the VRFCAT as important and meaningful for independent functioning in the community
VRFCAT data from several large industry drug treatment trials will provide data on the longitudinal properties (e.g., sensitivity to change) of the VRFCAT
These complementary new data collection efforts will be integrated with the existing evidence to support a formal qualification package to the FDA
1. Keefe, R.S.E., Davis, V.G., Atkins A.S., Vaughan, A., Patterson T., Marasimhan, M., Harvey, P.D. (2016). Validation of a computerized test of functional capacity. Schizophrenia Research, 90-96.
2. Ventura, J., Welikson, T., Ered, A., Subotnik, K.L., Keefe, R.S.E., Hellemann, G.S., Nuechterlein, K.H. (2019). Virtual reality assessment of functional capacity in the early coure of schizophrenia: Associations with cognitive performance and daily functioning. Early Intervention in Psychiatry, 1-9.
3. Nahum, N. (2019). Online plasticity-based social cognitive training for schizophrenia: A multi-site RCT. Paper presented at the Annual Cognitive Remediation in Psychiatry Meeting, New York, NY.
Baseline Mid-Assessment Post
900
800
1000
1100
1200
VRFC
AT
Control
SCV
VRFCAT in patients receiving Control (n = 71) vs. SocialVille (SCV; n = 76) interventions: SCV Cohen’s d = 0.51; Group X Time: b = -57.5, p = .025.
Treatment Study3IVRecent-Onset Schizophrenia Validation Study2
Age, Mean (Std Dev)
Male, N (%)
Non-Hispanic, N (%)
Years of education, Mean (Std Dev)
Parental education. Mean (Std Dev)
HC (N = 13)
21.92 (1.61)
4 (31%)
7 (53.8%)
14.43 (1.27)
13.08 (2.96)
SZ (N = 42)
23.05 (4.04)
31 (74%)
28 (70%)
13.04 (1.63)
14.38 (4.24)
III
VRFCAT Total Time T-Score
VRFCAT Total Errors T-Score
VRFCAT Progression T-Score
MCCB Composite T-Score
UPSA-2-VIM
GFS-Role functioning
GFS-Social functioning
.65**
.66**
-.70**
-.66**
-.52
-.43*
.83**
-.60**
-.53**
-.17
-.26
-.66**
-.62**
-.32
-.43
VRFCAT Total Time T-Score
VRFCAT Total Errors T-Score
VRFCAT Progression T-Score
Convergent validity within the recent-onset patients:Correlation analysis of the VRFCAT with MCCB, functional capacity (UPSA-2-VIM), and daily functioning (GFS) indicates a strong degree of correlation. *p < .05. **p < .01. Data from2
III
RECENT-ONSET SCHIZOPHRENIA SENSITIVITY TO CHANGE
Age, Mean (Std Dev)
Male, N (%)
Non-Hispanic, N (%)
English as Primary Language, N (%)
Unemployed, N (%)
Comfortable with PC, N (%)
Years of Education, Mean (Std Dev)
Mother’s Years of Education, Mean (Std Dev)
42.6 (13.93)
88 (53)
136 (82)
157 (95)
54 (33)
160 (97)
14.7 (2.41)
12.9 (2.98)
43.6 (11.84)
87 (55)
128 (81)
151 (96)
135 (85)
140 (89)
12.8 (1.99)
12.5 (3.33)
HC(N – 165)
SZ(N = 158)
Chronic Schizophrenia Validation Study1I V
Schizophrenia Patients Healthy Controls
Patients (N = 155) HC (N=163)
Assessments
VRFCAT Total Time T-score
VRFCAT Total Errors T-score
VRFCAT Progression T-score
MCCB Composite T-Score
UPSA-2-VIM
VRFCAT Total Time
T-score
VRFCAT Total Errors
T-score
VRFCAT Progression
T-scoreMCCB MCCB
---
0.70
0.71
0.57
0.56
0.77
---
0.65
0.39
0.41
0.59
0.73
---
0.45
0.43
0.69
0.54
0.38
---
0.70
0.65
0.56
0.41
0.75
---
Convergent validity: Correlation analysis of the VRFCAT and MCCB indicates a strong degree of correlation, comparable to the UPSA. All correlations p-values were < 0.001 (data from1).
III
Test re-test reliability for the VRFCAT and UPSA: Although reliability statistics were similar for the VRFCAT total time and UPSA, the UPSA demonstrated increased vulnerability to practice effects (data from1).
AssessmentsVisit 1
Mean (SD)Visit 2
Mean (SD)Cohen’s d
Intraclass Correlation Coefficient
(ICC)
VRFCAT Total Time T-score
VRFCAT Total Errors T-score
VRFCAT Progression T-score
UPSA-2-VIM*
50.1 (11.12)
49.7 (11.48)
49.8 (10.20)
83.4 (9.06)
32.3 (16.78)
37.1 (22.74)
40.4 (13.66)
70.7 (11.83)
50.9 (11.52)
49.8 (12.94)
50.3 (10.51)
86.7 (9.07)
31.8 (17.62)
36.7 (22.07)
40.8 (13.58)
74.5 (12.07)
0.07
0.01
0.05
0.36
-0.03
-0.02
0.03
0.32
0.65
0.54
0.29
0.75
0.81
0.65
0.61
0.78
HC SZ SZHC HC SZ SZHC
II IVdata from1
CHRONIC SCHIZOPHRENIA