Study to Establish the Psychometric Properties of the Digital Cognitive Tests on the Philips IntelliSpace Cognition Platform
Phase: NA
Conditions: Cognitive Functioning of Healthy Individuals
Sponsor: Philips Electronics Nederland B.V. acting through Philips CTO organization

20190082
Philips Research
PH I LIPSthe
Mar 01, 2019
Clinical Study Investigation Plan
PJ-011726 Study to establish the psychometric
properties of the digital cognitive tests on the
Philips IntelliSpace Cognition Platform
Document history
Version:
Date:
Author:
Description/Change/Reason for Change
0.1
09-08-2017
Laura Kiaming,
1
st version
Ben Schmand
0.2
24-08-2017
Daisy van Minde
2
nd version
0.3
07-03-2018
Laura Kiaming, Ron Dotsch
3d1 version
0.4
18-09-2018
Laura Kiaming,
4
th version
Ben Schmand
0.5
04-10-2018
Daisy van Minde,
5
th version
Murray Gillies
Ron Dotsch, Ben Schmand,
0.6
07-11-2018
James Hoidnack, Justin
6
th version
Miller, Daisy van Minde
0.7
14-11-2018
Mandy Spaltman
New template and few additions
0.8
16-11-2018
Daisy van Minde
8th version
0.9
29-11-2018
Daisy van Minde
9th version
Minor changes after ICBE secretary
0.10
06-12-2018
Mandy Spaltman
review
0.11
13-12-2018
Mandy Spaitman
Minor changes after ICBE review
Comments after pre-review ICBE and
0.12
14-12-2018
Daisy van Minde
from Q&R addressed.
Final draft before ICBE Board review
Added definition ‘norm data’ to chapter
0.13
19-12-2018
Gert-Jan Adriaans
3 as it is the main purpose of study and
reflecting to privacy assesment.
0.14
19-12-2018
Mandy Spaitman
Slight rephrasing of norm data definition.
1.0
21-12-2018
Mandy Spaitman
Removing markup for approved version.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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P11 I LI PS
2.0
18-02-2019
Mandy Spaitman
Edit to our sample size.
APPROVAL / PROTOCOL SIGNATURE SHEET
Function
Name
Signature !Date
(yyyy-mmm-dd)
Regulatory Representative of Sponsor
Marta Walker
Sr. Q&R Manager Philips HealthWorks,
Business Excellence
Principal Investigator
James Holdnack
(i.
Umcid
2O1-O3-Z
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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PHILIPS
ROLES / RESPONSIBILITIES
This section contains a list of all parties and persons involved in the Clinical Investigation.
Coordinating
investigator!
Project leader
Daisy van Minde
High Tech Campus 34.1.038
5656 AE Eindhoven, the Netherlands
Tel: +31646802217
Email: daisy.van.minde@philips.com
James Holdnack
5 Rose Hill Drive, Bear DE 19701
Principal investigator(s)
U.S.A
Tel: +1 (302) 312-4077
Email: iames.ho1dnackphi1ips.com
Investigational Site
N/A
Other participating sites
Several office rooms will be rented in the USA to conduct the study.
Sponsor (the individual
or organization taking
Philips Electronics Nederland B.V.,
responsibility and
acting through its Philips HealthWorks organization
liability for the initiation
High Tech Campus 34
or implementation of a
5656 AE Eindhoven, The Netherlands
clinical investigation)
Subsidizing party
N/A
Independent
physician(s)
N/A
(the Netherlands only)**
Laboratory sites
N/A
Co-investigators
.
Roel Cuppen
— Senior Architect
.
Mandy Spaltman
— Psychologist Researcher
.
Gijs van Elswijk
— Cognitive Scientist
.
Ron Dotch
— Cognitive Psychologist! Data scientist
.
Stefan Vermeent - Psychologist! Data scientist
.
Ben Schmand
— Professor in Clinical Neuropsychology
Appendix
.
A. Sampling plan
.
B. Validation ISC
— device list
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
j Status: Approved
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TABLE OF CONTENTS
APPROVAL! PROTOCOL SIGNATURE SHEET
2
ROLES / RESPONSIBILITIES
3
TABLE OF CONTENTS
4
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS
5
1 1 EXECUTIVE SUMMARY
7
2 INVESTIGATIONAL DEVICE
14
2.1 Device Summary
14
2.2 Intended purpose
16
2.3 Device Description
16
3 JUSTIFICATION
16
4 RISKS AND BENEFITS ASSESSMENT
19
I have created and uploaded a risk management summary matrix
19
5 OBJECTIVES AND HYPOTHESES
20
6 CLINICAL INVESTIGATION DESIGN
21
6. 1 General
21
6.2 Investigational device(s) and comparator(s)
23
6.3 Subjects
23
6.4 Procedures
24
Specimen Banking (saving human fluid or tissue for future research)
24
6.5 Monitoring plan
25
7 STATISTICAL CONSIDERATIONS
25
8 DATA MANAGEMENT
27
9AMENDMENTS
28
10 DEVIATIONS
28
11 DEVICE ACCOUNTABILITY
29
12 STATEMENTS OF COMPLIANCE
29
13 INFORMED CONSENT PROCESS
30
14 ADVERSE EVENTS AND DEVICE DEFICIENCIES
30
15 INVESTIGATOR BROCHURE (IB)
33
16 VULNERABLE POPULATION
33
Title: clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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P1—I I LI PS
17 SUSPENSION OR PREMATURE TERMINATION
33
18 PUBLICATION POLICY
34
19 BIBLIOGRAPHY
34
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS
ABR
ABR form, General Assessment and Registration form, is the application form required for submission to
the accredited Ethics Committee
In Dutch, ABR = Algemene Beoordeling en Registratie
AE
Adverse Event
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the
investigational medical device
AR
Adverse Reaction
CA
Competent Authority
Clinical
Systematic investigation in one or more subjects, undertaken to assess the safety and performance of a
Investigation
medical device
CIP
Clinical Investigation Plan
Document that state(s) the rationale, objectives, design and proposed analysis, methodology, monitoring,
conduct and record-keeping of the clinical investigation
NOTE: The term protocol” is synonymous with CIP”. However, protocol has many different meanings,
some not related to clinical investigation, and these can differ from country to country.
CFA
Confirmatory factor analyses
CFR
Code of Federal Regulations
CNS
Central Nervous System
COWAT
Controlled Oral Word Assocation Test
CRF
Case Report Form
Set of printed, optical or electronic documents for each subject on which information to be reported to the
sponsor is recorded, as required by the CIP
CV
Curriculum Vitae
DCDx
Digital Cognitive Diagnostics
DSMB
Data Safety Monitoring Board
EC
Ethics Committee
eCRF
Electronic Case Report Forms
ECT
Electroconvulsive therapy,
EDC
Electronic Database Capture
Endpoint
Principal indicator(s) used for assessing the primary hypothesis of a clinical investigation
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HCP
HealthCare Professional
HSDP
HealthSuite Digital Platform (Philips)
Hypothesis
Testable statement, resulting from the objective, regarding the investigational medical device safety or
performance used to design the clinical investigation and that can be accepted or rejected based on results
of the clinical investigation and statistical calculations.
NOTE: The primary hypothesis is the determinant of the investigational medical device safety or
performance parameters and is usually used to calculate the sample size. Secondary hypotheses
concerning other points of interest can also be evaluated.
ADL
Activity of Daily Living
lB
Investigator’s Brochure
IC
Informed Consent
The informed consent is documented by means of a written, signed and dated informed consent form.
The informed consent process is the process by which an individual is provided information and is asked to
voluntarily participate in a clinical investigation.
ID
Identification
IRB
Institutional Review Board
ISC
IntelliSpace Cognition
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 201 9-02-18
Status: Approved
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Investigator
Individual member of the investigation site team designated and supervised by the principal investigator at
an investigation site to perform critical clinical-investigation-related procedures or to make important clinical
investigation- related decisions.
NOTE: An individual member of the investigation site team can also be called “sub-investigator” or “co
investigator”.
MMSE-2
Mini Mental Status Exam 2
MoCA
The Montreal Cognitive Assessment
Objective
Main purpose for conducting the clinical investigation
Point of
Time at which, following recruitment, a subject signs and dates the informed consent form
enrollment
QMS
Quality Management System
ROCFT
Rey Osterrieth Complex Figure Test
SAE
Serious Adverse Event
Adverse event that
a) led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1) a life-threatening illness or injury, or
2) a permanent impairment of a body structure or a body function, or
3) in-patient or prolonged hospitalization, or
4) medical or surgical intervention to prevent life-threatening illness or injury or permanent
impairment to a body structure or a body function,
c) led to foetal distress, foetal death or a congenital abnormality or birth defect
NOTE Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without
serious deterioration in health, is not considered a serious adverse event.
Sponsor
Individual or organization taking responsibility and liability for the initiation or implementation of a clinical
investigation
TBI
Traumatic Brain Injury
TMT
Trail Making Test
USA
United States of America
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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11 EXECUTIVE SUMMARY
Study Title & ID
PJ-01 1726 Psychometric properties of IntelliSpace Cognition
Full title: Study to establish the psychometric properties of the
digital cognitive tests on the Philips IntelliSpace Cognition
Platform
.
N/A
Project Name
.
This study aims to validate the tests that are on the IntelliSpace
Brief Summary of Study
Cognition platform and to establish normative data for these tests.
Provide a lay-language abstract of
your study plan (100-300 words)
.
Cognitive model
Key Words Associated with
Study
Cognitive assessment
Digital cognitive tests
Provide 3-5 PubMed MeSH
Automated scoring
keywords
Algorithms
Country(s) from where the
1 Netherlands
USA
El Germany
Li China
data originates (where
LI India
Li Belgium
LI UK
LI Kenya
collected)
LI Other:
This study will be conducted per the requirements of ISO
14155
This study WILL NOT be conducted per the requirements of
ISO 14155. For example studies formerly known as H-lite and
J-Lite
This study has no clinical primary or secondary objectives.
However the data generated from this study will be used as
ground data in a Device class Il according to regulation CFR21
ISO 14155 compliance
Sec. 882.1470 Computerized cognitive assessment aid.
Therefore Philips will follow ISO 14155, Good Clinical Practice in
all applicable requirements.
Data generated from this trial will be monitored and will be Part 1 1
compliant.
Important note 1: There are no foreseeable risks or possible
adverse events in this study. This is a non-significant risk study.
The study will be submitted to lOBE and IRB review /approval.
Is this study part of a
No
student projectlthesis?
LI Yes, Student Name:
University:
Primary objective
The study has four aims.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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1. To compare the psychometrics of digital and paper-pencil
cognitive tests. Score distributions, test-retest reliability, and
construct validity of the following tests will be compared: Trail
Making Test (TMT), Rey Osterrieth Complex Figure Test
(ROCFT), Digit Span Test, Controlled Oral Word Association Test
(COWAT), Category Fluency Test, Rey Auditory Verbal Learning
Test (RAVLT), Clock Drawing Test, Star Cancellation Test, 0
Cancellation Test, Mini Mental Status Exam 2 (MMSE-2).
2. To assess the degree of agreement between the algorithm and
manual scores for the digital Rey Osterrieth Complex Figure Test
and Clock Drawing Test.
3. To estimate regression-based norms and reliable change
indices.
4. To estimate factor loadings for a structural equation model
describing cognition in terms of distinct cognitive domains
Secondary objective(s)
The secondary objective of the study is to explore usability
aspects of IntelliSpace Cognition.
Participating parties and
Sponsor: Philips Electronics Nederland B.V.,
their roles
•
Internal Ethics approval
•
Providing Principal Investigator
•
Study Design
•
Monitoring
•
Data storage
•
Data integrity check
•
Data analysis
•
Report
Study co-ordinator:
•
Selection of rooms for data collection
•
Selection of psychometrists
•
IRB approval
•
Recruitment of participants
•
Data collection
Subjects
The study will include at minimum N400 and up to N=450
healthy participants who will be sufficiently distributed across
gender, ages 55 to 80 for validation data and ages 50 to 80 for
normative data, ethnicity, and education level to reflect the
distribution of people that will typically be assessed with
IntelliSpace Cognition.
As this study is in preparation of selling a reliable product, we aim
to obtain norms based on a sample that adequately reflects the
US population.
A variety of standard techniques will be used to recruit
participants.
Title: Clinical Investigation Plan
Author: Laura Kiaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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Inclusion Criteria:
•
Examinee’s primary language (language most often spoken)
must be English.
•
If examinee has vision impairment or hearing loss, must be
corrected to normal.
•
Must have normal fine and gross motor ability
•
Must have use of fingers, hands, and arms to be able to use a
pencil to write symbols.
•
Must be able to understand subtest instructions and
participate fully in testing.
Exclusion Criteria:
•
Evidence of current cognitive impairment.
•
Disruptive behavior or insufficient compliance with testing to
ensure a valid assessment.
•
Examinee must not be currently admitted to a hospital,
assisted living, nursing home or a psychiatric facility.
•
Examinee must not be diagnosed with a neurological disorder
or disease (e.g., Parkinson’s, brain tumor, stroke, TBI,
epilepsy [if # seizures
2 and not receiving ongoing treatment
for seizures, and not currently seeking medical evaluation or
attention related to seizures, examinee can be accepted],
encephalitis, dementia, language disorder (expressive or
mixed receptive/expressive excluded; articulation disorder is
ok), learning disorder.
•
Must not have been unconscious related to traumatic brain
injury or “medical condition” > 20 minutes (however, e.g., heat
stroke, medication induced are Ok) or any head-injury
resulting in an overnight hospital stay.
•
Any history of a medical event requiring resuscitation in which
examinee was non-responsive for> 15 minutes.
•
Must not have current or recent functional change (ability to
carry out usual duties at work, in school, IADLs [driving,
shopping, managing money], etc.) due to cognitive change.
•
Examinee must not be receiving chemotherapy treatment, or
have received chemotherapy treatment in the past 2 months.
•
Examinee must not have a history of ECT or radiation to the
CNS.
•
Examinee must not be (currently or in the past) diagnosed
with a psychotic disorder, or currently diagnosed with a mood
disorder (however, Major Depressive Disorder in remission or
with no current episode, and Dysthymic and Adjustment
Disorders, are acceptable) or an anxiety disorder with
symptoms significant enough to interfere with optimal test
performance.
•
Autoimmune disorder (e.g., LUPUS, Multiple Sclerosis)
•
Exam inee must not be currently diagnosed with substance
abuse or dependence, or have carried any substance abuse
or dependence diagnosis in the past year (> 1 year in
remission diagnoses are Ok). Long term alcohol abusers are
excluded as well (e.g., abused substance for more than 10
years).
•
Any history of Autism Spectrum Disorder or Intellectual
Disability.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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•
The examinee must not be currently taking medication that
might impact test performance (e.g., anti-convulsants,
antipsychotics, benzodiazepines, psychostim ulants, opiods,
tricyclic antidepressants, some norepinephrine reuptake
inhibitors). Most antihypertensive medications and statins are
acceptable.
•
If previously diagnosed with any physical condition or illness
that might depress test performance, illness must not interfere
with normal cognitive functioning at work, school, ADLs, etc.
Diabetes, hypothyroidism, and hypertension are acceptable if
controlled.
•
Exclude primarily nonverbal or uncommunicative. Must not
have a diagnosis of aphasia.
•
Examinees should not have received neuropsychological
testing although previous MMSE testing is allowed if more
than 6 months prior
•
Exam inee must not be seeking medical diagnostic procedures
for cognitive difficulties from a medical professional.
•
Non-valid health insurance in USA.
Investigation design
The study has a randomized, counterbalanced design with two
conditions to which participants will be assigned randomly with
minimization for demographic variables.
Investigation procedures
The study consists of two phases. All participants in phase 1 will
be invited to participate in two assessments that will take place
with a time interval of two weeks between the two time points to
minimize retest effects. Participants (total N = 400) will be
randomly assigned to one of the following groups:
-
Group A (n=100) completes digital tests in phase 1 and
paper-pencil tests in phase 2,
-
Group B (n100) completes paper-pencil tests in phase 1
and digital tests in phase 2,
-
Group C (n50) completes digital tests in both phases,
-
Group D (n=50) completes paper-pencil tests in both
phases,
-
Group E (n=100) only completes digital tests in one phase
(50% of group E will be enrolled in phase 1 and the other
50% of group E will be enrolled in phase 2).
If the timeline allows for it, up to 50 additional participants aged
50-54 will be included in group E to stretch the age range for the
regression-based norms, making the group size up to n150 and
the total sample size up to N = 450.
The data of group A and B are used to compare score
distributions within-subjects.
The data from groups A-D (phase 1) are used to compare score
distributions between-subjects (aim 1).
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 201 9-02-18
Status: Approved
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PHILIPS
The data of group C and D are used to assess and compare test-
retest reliability (aim 1) and assess reliable change indices (aim
3).
The data of group A (phase 1), group C (phase 1) and group E
are used to estimate regression based norms for the digital tests
(aim 3), as well as to estimate factor loadings for the structural
equation model (aim 4).
The data of group A (phase 1), group B (phase 1), group C (phase
1) and group D (phase 1) are used to compare construct validity
(aim 1).
Participants will be randomized with minimization for demographic
variables (gender, age, education level, ethnicity).
Assuming a dropout rate of 20% we will oversample our desired N
by the same percentage, resulting in sampling of 480 participants.
The completed tests will be scores by two well-trained raters, with
double scoring of 30% of participants to assess inter-rater
agreement.
Scoring algorithms for the ROCFT and the Clock Drawing Test are
applied post-data collection. The scores estimated by the
algorithms will be compared with manual scoring by a sample of
well-trained raters (n = 6; aim 2). The data collected during this
study are only used for validation and not used in any way to train
these scoring algorithms.
Each assessment will last approximately 1.5 hours.
At-Home Subject
Procedures
Devices
Check each box as appropriate
and add a brief description of
the device(s)—e.g., fitness
tracker, VR goggles, breast
pump, electric toothbrush,
ELAN, MRI scanner.
NOT APPLICABLE
None
Mock-up (see ICBE FAQ definition):
Survey/questionnaire (if copyrighted, ensure permission for
use):
Usability questionnaire
Interview/focus group with audio/video taping**:
Interview/focus group without audio/video taping**:
**see decision flowchart regarding interviews vs QI vs consulting
https://share-intra.philips.com/sites/STS2O 13111 5093003/ICBE-
FAO/Lists/Photos/interviews%20criteria%20flowchart%2Ofeb2Ol 8.
Devices will be described fully
in Section 2.1 of the study
protocol.
FDA or CE-approved medical
device within intended use:
J FDA or CE-approved medical
device outside intended use:
FDA or CE-approved non-
medical device within intended
The digital tests will be provided to the
use:
A
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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participants on an Ipad Pro (Apple). It has a screen size of12.
9
-inch with a
screen resolution of 2732x2048. Participants will use the Apple pencil for the
Ipad Pro to perform the tests (see Figure). Both the iPad Pro as well as the
Apple Pencil are wiped clean after use by each participant.
To digitally administer the digital tests to the participants, the test leader will
start the test via the software prototype on a regular laptop that will be
provided by Philips (see Figure).
The Ipad pro, Apple pencil and the regular laptop will all be commercially
available devices and used within their intended use.
FDA or CE-approved non-medical device outside intended
use:
In vitro medical device:
Medical device prototype***:
Non-medical device prototype***:
Software prototype***, non-medical:
A selection of the digital tests are administered to the participants via a
software prototype designed by Philips (Production Equivalent Device).
Software prototype***, medical:
A selection of the digital tests is administered to the participants via a medical
software prototype (on an iPad) designed by Philips (IntelliSpace Cognition).
LI Other:
***Before a study employing prototypes may start, a Declaration of
Conformity (D0C) needs to be issued by the Director
Regulatory Affairs. With this DoC, Philips declares that the
device can safely be used in the study. It may be needed to
work according to some formal standards to build up this
evidence (e.g. with respect to bio-compatibility or sterility).
DoC needed (brief overview of the actions that will be taken
to get the Declaration of Conformity. See Philips Research QMS
procedure “Procedure Product Release (QR-PRO-36”. Give
details of how the project will deal with the regulatory
requirements. Consult the Q&R office when needed):
Milestones
ICBE review will be completed 17 December 2018
IRB review will be completed 15 Feb 2019
Data collection will start in 15 March 2019
Data collection for time point 1 will be completed 15 June 2019
(with four examiners)
Data collection for time point 2 will be completed 15 Sept 2019
(with four examiners)
Data analysis will be completed 15 October 2019
Report will be completed 15 October 2019
Claims
Will you obtain regulatory (FDA, CE) approval for a new product or
service, a new indication, or a new marketing claim?
Li Yes
No N/A 510K exempt
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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If YES, in what countries will the claims be registered?
El Netherlands
USA
El Germany
El China
El India
El Belgium
El UK
El Kenya
El Other:
Have you developed a list of claims that you would like to assert
for your product or service?
Yes
El No
.
El Not Required (not a local/state/country requirement)
External Research Ethics
Required (apply for it AFTER ICBE approval)
Committee (REC) Approval
El Approval already obtained (upload for review by ICBE)
Note: if your document is not in
El
REC Review is waived (upload review waiver)
English or Dutch, include an English
El
REC has waived requirement for informed consent (upload
transiation
waiver)
El Check this box if more than one REC is involved in this study
and_identify_them:
Submission to Competent
Not applicable (510K exempt)
Authorities
Check the applicable option concerning Competent Authority
approval for medical device studies:
El No submission to Competent Authority needed, since no non-
released medical device involved
El Approval from Competent Authority is mandatory for this study
with a non-released medical device
Note: Released medical device means a device that is e.g. CE-
marked (93/42/EEC) if study takes place in EU, or has 510k if
study takes place in USA.
Our device will be marketed as a Class-Il Medical Device in the
US. The device is 510(k) exempt by the FDA.
Link: https://www.accessdata.fda.gov/scripts/cdrh!cfdocs/cfPCD/cla
ssification.cfm?id3768
Database registration
El None
ClinicalTrials.gov
El Other:
Type of Legal Agreement
El None required
El MRA Exhibit
for this study
Contract
Purchase Order
We will work with a CR0 (supplier) via a purchase order and
additional CR0 agreement
Status of Legal Agreement
El NA
El Not started
In Process
El In Place
Name of Legal Rep: Jennifer Nene
lP Strategy
See CR0 agreement
ICBE Training is required
.
.
.
*
YES, this training is completed as required by ICBE
for all key study personnel
El NO, this training is not completed as required by ICBE*:
Title: Clinical Investigation Plan
Author: Laura Kiaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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2 INVESTIGATIONAL DEVICE
2.1 Device Summary
This chapter contains a summary description of the investigational device and its intended purpose.
Summary device
Philips IntelliSpace Cognition (ISC) is a digital proposition from the Digital
description
Cognitive Diagnostics (DCDx) venture.
It is a digital aid which supports
HealthCare Professionals (HCP5) in assessing the cognition of individuals
within a healthcare facility. It consists of two interfaces connected to the DCDx
module in the cloud. ISC will be hosted on the Health Suite Digital Platform
(HSDP). The first interface is the patient’s interface and is presented via a tablet
to collect data on how the patient performs a series of tests. The second
interface is the clinician’s interface and is typically located on a laptop. It allows
for tests or test batteries to be selected, observations noted, data analytics
performed and the generation of a report. Philips ISC is a Class-Il Medical
Device in the US and provides objective data regarding cognition via scoring
algorithms that HCPs can use to inform diagnostic decision making and
treatment planning.
It enables tracking cognition over time and offers the
possibility of new outcome measures. ISC can be used in a variety of healthcare
environments such as neurology and neuropsychology practices.
In this study 4 devices/tools will be used:
•
A version of the ISC medical product (as engineered in accordance
with the HealthWorks QMS) and that is verified to be used for data
collection and provides the interface of the final product for the tests:
TMT, Clock Drawing Test, MMSE-2, ROCFT, and Digit Span Test.
•
A production equivalent (research platform) that provides: 0
Cancellation Test, Category Fluency Test, RAVLT, COWAT and Star
Cancellation.
•
Paper tests: Trail Making Test, Rey Osterrieth Complex Figure Test,
Digit Span Test, Controlled Oral Word Association Test, Category
Fluency Test, Rey Auditory Verbal Learning Test, Clock Drawing Test,
Star Cancellation Test, 0 Cancellation Test, MMSE-2. In addition a
naming test in paper format will also be included.
•
A MoCA paper based screener test.
In this study, these devices/tools will be used to investigate score distributions,
construct validity and test-retest reliability.
Summary
The lntelliSpace Cognition tool is intended to be used as an adjunctive tool in
intended purpose
the assessment of an adults’ level of cognitive functioning.
The IntelliSpace Cognition tool provides health care professionals with an
overview of both the overall cognitive performance as well as specific
cognitive domains.
The IntelliSpace Cognition tool provides health care professionals with a
method to compare a person’s cognitive performance over different
assessments (moments in time).
Title: Clinical Investigation Plan
Author: Laura Kiaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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The results from IntelliSpace Cognition tool are intended to be used by
healthcare professionals who have participated in IntelliSpace Cognition
trainings.
The data collected by lntelliSpace Cognition are intended to be collected
under the supervision of a HCP.
The lntelliSpace Cognition tool is not intended as a stand-alone or adjunctive
diagnostic device.
The assessments provided via the IntelliSpace Cognition tool may be used for
a wide variety of patient groups, as well as healthy individuals when a HCP
wishes to gain more insight into cognitive performance.
The cognitive model of IntelliSpace Cognition tool has been
scientifically validated for assessing the cognition of healthy people in
the age group of 55-80.
The IntelliSpace Cognition tool has not been validated for use with
adults under the age of 55 or over the age of 80 and doesn’t include
normative data for adults under the age of 50 or over the age of 80.
Maintenance of the device will be carried out by Philips employees. Cleaning
of the device will be carried out as needed by the investigators. When the
device is not used for the clinical investigation it is placed inside a locked
cabinet in a locked office at the sites. At clinical investigation termination or
Disclaimer:
.
Population
The tests provided via the IntelliSpace Cognition may be used for anyone
description
where an overview of cognitive functioning is required provided they are part
of the demographic group as described in the section titled “subjects”.
Manufacturer
The legal manufacturer is Philips HealthWorks for which FDA 21 CFR 820.30
compliant design control will be implemented to allow for clinical validation of
the device as part of 21 CFR 820.12 Investigational Device Exemptions.
Device
A released version of the ISC product (as engineered in accordance with the
modelltype
HealthWorks QMS) and that is verified to be used for data collection and
provides the interface of the final product for the tests: TMT, Clock Drawing
Test, MMSE-2, ROCFT and Digit Span Test.
A production equivalent (research platform) that provides: 0 Cancellation
Test, Category Fluency Test, RAVLT, COWAT and the Star Cancellation.
Software version
Software version 1.0.0 of the ISC product will be released for the clinical
investigation.
Software version 3.10.6A of the product equivalent will be used for the clinical
investigation.
Accessories
iPad Pro tablets (Apple)
Apple pencils
Regular laptops
Traceability
procedure
Title: Clinical Investigation Plan
Author: Laura Kiaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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closure, the device will be returned to Philips and checked by the Monitor. The
devices, SW and accessories are uniquely identified and listed in appendix B
Validation ISC
— device list.
Required training
Persons qualified to administer the neuropsychological tests, i.e. a
psychologist or psychometrist, will use the investigational devices to collect
data as part of the clinical investigation. Employees of Philips will train the
researchers for operation of the investigational devices.
Specific
N/A
procedure acts
Device Labeling
The software will contain a label with the text; not for clinical use.
2.2 Intended purpose
The IntelliSpace Cognition tool is intended to be used as an adjunctive tool in the assessment of an
adults’ level of cognitive functioning.
The IntelliSpace Cognition tool provides health care professionals with an overview of both the overall
cognitive performance as well as specific cognitive domains
The IntelliSpace Cognition tool provides health care professionals with a method to compare a
person’s cognitive performance over different assessments (moments in time).
The results from IntelliSpace Cognition tool are intended to be used by healthcare professionals who
have participated in IntelliSpace Cognition trainings.
The data collected by IntelliSpace Cognition are intended to be collected under the supervision of a
HCP
The IntelliSpace Cognition tool is not intended as a stand-alone or adjunctive diagnostic device.
The assessments provided via the IntelliSpace Cognition tool may be used for a wide variety of patient
groups, as well as healthy individuals when a HCP wishes to gain more insight into cognitive
performance.
Disclaimer:
•
The cognitive model of IntelliSpace Cognition tool has been scientifically validated for
assessing the cognition of healthy people in the age group of 55-80
•
The IntelliSpace Cognition tool has not been validated for use with adults under the age of 55
or over the age of 80 and doesn’t include normative data for adults under the age of 50 or over
the age of 80.
2.3 Device Description
Philips IntelliSpace Cognition (ISC) is a digital proposition from the Digital Cognitive Diagnostics
(DCDx) venture. It is a digital aid which supports HealthCare Professionals (HCPs) in assessing the
cognition of individuals within a healthcare facility. It consists of two interfaces connected to the DCDx
module in the cloud. ISC will be hosted on the Health Suite Digital Platform (HSDP). The first interface
is the patient’s interface and is presented via a tablet to collect data on how the patient performs a
series of tests. The second interface is the clinician’s interface and is typically located on a laptop. It
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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allows for tests or test batteries to be selected, observations noted, data analytics performed and the
generation of a report. Philips ISC is a Class-Il Medical Device in the US and provides objective data
regarding cognition via scoring algorithms that HOPs can use to inform diagnostic decision making
and treatment planning. It enables tracking cognition over time and offers the possibility of new
outcome measures. ISC can be used in a variety of healthcare environments such as neurology and
neuropsychology practices.
In this study 4 devices/tools will be used:
•
A version of the ISC medical product (as engineered in accordance with the HealthWorks
QMS) and that is verified to be used for data collection and provides the interface of the final
product for the tests: TMT, Clock Drawing Test, MMSE-2, ROCFT, and Digit Span Test.
•
A production equivalent (research platform) that provides: 0 Cancellation Test, Category
Fluency Test, RAVLT, COWAT and Star Cancellation.
•
Paper tests: Trail Making Test, Rey Osterrieth Complex Figure Test, Digit Span Test,
Controlled Oral Word Association Test, Category Fluency Test, Rey Auditory Verbal Learning
Test, Clock Drawing Test, Star Cancellation Test, 0 Cancellation Test, MMSE-2. In addition a
naming test in paper format will also be included.
•
A MoCA paper based screener test.
In this study, these devices/tools will be used to investigate score distributions, construct validity and
test-retest reliability.
The ISC production equivalent that will be used for administering 0 Cancellation Test, Category Fluency
Test, RAVLT, COWAT and Star Cancellation has the exact same patient interface as the end-product.
The digital tests will be provided to the participants on an iPad Pro tablet (Apple). It has a screen size
of 12.9-inches with a screen resolution of 2732x2048. This is the exact same tablet as required for use
of the final ISC product.
Participants will use the Apple pencil for the iPad Pro tablet to perform the digital tests (see Figure 1).
The tablet will present instructions for each test to participants via both written text and audio
recordings. A researcher will observe in order to ensure that the participant understands and follows
the instructions (see Figure 2). The iPad Pro tablet, Apple pencil and the regular laptop, which may be
used by the researcher to take notes, are all CE marked devices.
Figure 1. Pad pro and Apple pencil used by the participant
Figure 2. Regular laptop used by researcher
The ISC production equivalent and ISC product (verified for data collection, SW version 1.0.0) are only
utilized to collect data. The scoring algorithms for the ROCFT and the Clock Drawing Test have either
not yet been implemented or the output of those that have been implemented will not be considered
relevant. The data collected with the device during the clinical investigation will be used to assess the
equivalence of outputs from automatic scoring by the algorithms to traditional manual scoring. Only
when the output of the algorithms have high agreement with manual scores of the respective test, the
algorithms will be integrated into the final ISC product.
3 JUSTIFICATION
While the ISC product may be used in a variety of situations the most likely is within a neurology office.
The use-case for ISC is that the raw data are collected via the ipad under the supervision of an assistant.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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Subsequently, various algorithms are applied to score the individual tests. These scores are then fed
into a cognitive model, resulting in easy-to-interpret cognitive domain scores. The domain scores are
norm referenced by age, and optionally by gender, education, and ethnicity. The output of ISC is used
by the neurologist to help him/her arrive at his/her diagnosis or for creating an optimal therapy plan. In
the case of recurring visits the cognitive domain scores give the neurologist (or HOP) metrics to
objectively assess change over time.
A USA neurologist will on average send 13% of his patients for a full neuropsychological assessment
while in an ideal world he/she would like to send 36% (The MarkeTech Group, 2018). A common reason
for not referring for a full assessment is the waiting time of 3-6 months (The MarkeTech Group, 2018).
There is a clear unmet need for a solution that gives more information than a simple screener tool but
within an actionable time-window, preferably during the patient vist. For the majority of patients, ISO
doesn’t replace the full neuropsychological assessment but instead helps triage patients so that people
that need a full assessment can be quickly identified and fast tracked.
In current clinical practice, neurologists perform an MMSE or MoCA screener and occasionally a
haphazard cognitive test such as a clock drawing or a simple word recall trial. In general the neurologist
does not possess the skill (or time) to score tests and normative data are rarely used. Computerized
cognitive assessment can alleviate issues with haphazard cognitive testing and allow more accurate
cognitive assessments to be performed at the neurology office. Digitized cognitive tests have a number
of important benefits compared to paper-pencil tests including norm scores at the level of cognitive
domains, continuous norm scores over age, more standardized administration and scoring, dynamic
presentation of the test content according to the abilities of the patient, more sensitive measurement of
reaction time, additional and potentially more sensitive outcome measures, and the possibility to replay
test performance (Bauer et al., 2012; Klaming & Vlaskamp, 2017; Miller & Barr, 2017; Schatz &
Browndyke, 2002).
The heart of IntelliSpace Cognition is the cognitive model. The model is based on structural equation
modelling, has its roots in published literature and knowledge gleaned from key opinion leaders in
neuropsychology. This provided mappings between test measures and the specific cognitive domains.
These mappings were fit to the data of 148 healthy individuals in an early stage pilot in the Netherlands,
and showed excellent fit. Moreover, the cognitive domains specified by the model demonstrated
sensitivity to impairment in 51 stroke patients and 48 TBI patients. The model is currently based on
accepted test measures. In the future it may be possible to incorporate new (to be validated) outcome
measures into the model and so make it more sensitive or reduce the number of tests needed. For
example in current neuropsychological clinical practice, interpretation of TMT performance is mostly
restricted to total completion time and errors. Other behaviours during TMT performance are likely to
reveal additional information, primarily about executive functioning, but in the current paper-pencil based
format of the test it is difficult or impossible to measure these behaviours. Research has already started
to look into new outcome measures for the TMT that are possible with digital measurement such as
inter-element variability and a separation of layout-related processes from executive processes on TMT
B (Klaming & Vlaskamp, 2017). In addition, digital assessment enables more accurate measurement of
total completion time and a more standardized assessment of errors during performance of the test.
Another example of a digital test is the digital administration of the ROCFT which provides a number of
important benefits over paper-pencil administration. Probably most importantly, digital administration
enables automatic scoring of the drawing which not only saves time in the scoring of the test, but
moreover contributes to better standardization of scoring. Additionally, it will be possible to implement
different scoring algorithms including both quantitative and qualitative scoring algorithms. In current
neuropsychological clinical practice, formalized qualitative scoring is only rarely performed despite the
fact that qualitative scoring provides additional information about the patient’s cognitive functioning
beyond the information provided by quantitative scoring (Akshoomoff & Stiles,
1995; Anderson,
Anderson, & Garth, 2001; Bennett-Levy, 1984; Chiulli, Haaland, Larue, & Garry, 1995; Deckersbach et
al., 2000; Hamby, Wilkins, & Barry, 1993; Shorr, Delis, & Massman, 1992). Besides automatic scoring
which would save time and decrease variability in scoring for both qualitative and quantitative scoring
systems, digital administration allows for the extraction of additional data such as touch/pencil pressure
and speed which may provide additional information about the patient’s cognitive functioning. The use
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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of computerized neuropsychological assessment has been recommended (Bauer et al., 2012; Miller &
Barr, 2017; Strauss, Sherman, &Spreen, 2006).
The lSC cognitive model is based on mappings between cognitive domains and established outcome
measures from well known paper-pencil tests which have many years of validation. It is vital for the
validity of the digital tests, the cognitive model and their subsequent use in clinical practice that the
comparibility between the digital tests on the ISC platform and the corresponding paper-pencil tests is
shown. This study aims at investigating the comparibility of the relevant digital and paper-pencil
cognitive tests, establishing the psychometric properties of the digital cognitive tests and collecting
normative data for the digital tests so that the digital tests and the cognitive model can be used in
clinical practice.Normative data is data from a reference population that establishes a baseline
distribution for a score or measurement, and against which other scores or measurements can be
compared. For this objective, data subjects are informed on the data we collect and the possible re
use of this data, including by 3rd parties.
4 RISKS AND BENEFITS ASSESSMENT
I have created and uploaded a risk management summary matrix
I have created and uploaded a risk management plan
A summary overview of the risks and benefits of the investigational device and the clinical procedure
aDDlied in this clinical investioation are listed in the table below.
Anticipated clinical
IntelliSpace Cognition is a digital tool to assess cognition in an efficient
benefits
way. It replaces the paper workflow by a digital workflow in a healthcare
facility.
Anticipated adverse
There are no risks of any adverse event, mild or serious
device effects
Residual risks
- No risk for participants
associated with
investigational device
-Data loss (risk for validity)
[as identified in risk
analysis report]
Risks associated with
- Privacy breach when devices are stolen and the system is not being
participation in clinical
logged off
investigation
- Fatigue during participation (risk is almost zero)
Possible interactions
There are no interactions with concomitant medical treatments
with concomitant
medical treatments
Steps that will be taken
- Privacy breach when devices are stolen and the system is not being
to control or mitigate
logged off
— systems will be logged off and stored in a locked cabinet
risks
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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- Fatigue during participation - protocol will include a short break to
prevent fatigue
Risk-to-benefit
There are no substantial risks or potential risks possible in this trial for
rationale
participants and there are no risk of any adverse event, mild or serious.
The benefits will be to be able to launch IntelliSpace Cognition and in
short; speed up the cognitive access process in clinics with use of
Artificial lnteligence, by replacing the paper based workflow by a digital
one and it will better triage patients /subjects to which ones needs a
more robust cognitive assessment with a neuropsychologist.
The benefits of the use of the investigational device outweigh the risks.
S OBJECTIVES AND HYPOTHESES
This chapter describes the objectives and hypotheses of the clinical investigation, as well as the
claims and intended performance of the investigational device to be verified, and the risks and
anticipated adverse device effects to be assessed.
Primary objective:
The study has four aims.
1. To compare the psychometrics of digital and paper-pencil cognitive tests. Score distributions, test-
retest reliability, and construct validity of the following tests will be compared: Trail Making Test (TMT),
Rey Osterrieth Complex Figure Test (ROCFT), Digit Span Test, Controlled Oral Word Association Test
(COWAT), Category Fluency Test, Rey Auditory Verbal Learning Test (RAVLT), Clock Drawing Test,
Star Cancellation Test, 0 Cancellation Test, Mini Mental Status Exam 2 (MMSE-2).
2. To assess the degree of agreement between the algorithm and manual scores for the digital Rey
Osterrieth Complex Figure Test and Clock Drawing Test.
3. To estimate regression-based norms and reliable change indices.
4. To estimate factor loadings for a structural equation model describing cognition in terms of distinct
cognitive domains.
Secondary objective(s)
The secondary objective of the study is to explore usability aspects of IntelliSpace Cognition.
Primary hypotheses
The following primary hypotheses will be tested in the study:
Aim 1.
A.
Digital and paper-pencil normed test scores are comparable. We consider the two versions of a
test comparable when the digital normed score is on average within .3 sd of the paper normed
score and the two normed scores correlate at least .6.
B.
Test-retest reliability of the digital tests is comparable to test-retest reliability of the paper-pencil
tests. We consider the reliability to be comparable when we observe no significant difference in a
z-test between the digital and the paper-pencil test-retest correlations.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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C.
Construct validity of the digital tests is comparable to the construct validity of the paper-pencil
tests. We consider construct validity to be comparable when confirmatory factor analysis yields the
same factor structure for digital and paper-pencil tests.
Aim 2.
D.
The score(s) provided by the ROCFT and Clock Drawing Test scoring algorithms on ISC are
correlated highly (> .8) to the score provided by manual scoring for the same drawings.
Aims 3 & 4 have no accompanying hypotheses.
Secondary hypotheses
The following secondary hypothesis will be tested in the study:
1.
The usability of the ISC device is sufficient for participants or psychologists/psychometrists.
This will be explored with a questionnaire for participants as well as a registration by the
psychologist/psychometrist of how many participants were unable to complete a test and why.
Claims and intended performance
The study aims to provide information that can be used to substantiate the claims listed in the table
below from the regulatory plan of ISC, along with the study aim covering the claim.
Claim
Description
Covered by
Study Aim
A scientific model developed with KOLs that translates raw test scores to
4
cognitive domains
Automated scoring algorithms that give reproducible scores time after time
2
Digital tests have similar psychometrics to paper test measures
1
Longitudinal reporting of performance at the level of cognitive domains
3 & 4
Usability by Design — high “easy to use” score for elderly users
Secondary objective
Usability by Design
- high user satisfaction when using digital platform
Secondary obJectiveA
Risks and adverse device effects:
The following risks and anticipated adverse device effects to be assessed:
•
Privacy breach
•
Participant fatigue
•
Data loss
6 CLINICAL INVESTIGATION DESIGN
6. 1 General
The study has a randomized, counterbalanced design and consists of two phases (see figure 1). We
sample participants according to the sampling plan outlined below, to ensure representativeness of
the sample. We will oversample by 20% to account for dropout or incomplete data (the n’s below
represent the desired cell counts, after dropout).
Figure 1. Schematic overview of study design.
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
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Group
A
B
C
D
E
100
100
50
50
100-1 50
Digital
Paper-
Digital
Paper-
Digital
pencil
pencil
Paper-
Digital
Digital
Paper-
pencil
pencil
All participants of Group A-D in phase 1 will be invited to participate in two assessments that will take
place with a time interval of four-five weeks between the two phases to minimize retest effects.
Participants will be randomly assigned with minimization for demographic variables (to make sure that
the groups do not differ in terms of gender, age, education level, and ethnicity) to one of the following
groups:
-
Group A (n=100) completes digital tests in phase 1 and paper-pencil tests in phase 2,
-
Group B (n—lOG) completes paper-pencil tests in phase 1 and digital tests in phase 2,
-
Group C (n=50) completes digital tests in both phases,
-
Group D (n50) completes paper-pencil tests in both phases,
-
Group E (n=100-150) only completes digital tests in one phase (50% of group E will be
enrolled in phase 1 and the other 50% of group E will be enrolled in phase 2).
The data of group A and B are used to compare score distributions within-subjects
The data from groups A-D (phase 1) are used to compare score distributions between-subjects (aim
1).
The data of group C and D are used to assess and compare test-retest reliability (aim 1) and assess
reliable change indices (aim 3).
The data of group A (phase 1), group C (phase 1) and group E are used to estimate regression based
norms for the digital tests (aim 3), as well as to estimate factor loadings for the structural equation
model (aim 4).
The data of group A (phase 1), group B (phase 1), group C (phase 1) and group D (phase 1) are used
to compare construct validity (aim 1).
Participants will be randomized with minimization for demographic variables (gender, age, education
level, ethnicity).
The purpose of adding the 100-150 participants in Group E is to increase the sample size of
participants who completed the digital tests for the first time for the norm data to 250-300.
We will use the 100 sets of digital ROCFT and Clock Drawing Test drawings, randomly drawn from the
full sample, to establish agreement between scoring algorithms and manual scoring by well-trained
raters (aim 2).
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 201 9-02-18
Status: Approved
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6.2 Investigational device(s) and comparator(s)
The investigational devices are the ISC product and the ISO product equivalent. The comparators are
the paper-pencil tests included in the study.
Manual scores of the digital ROCFT and Clock Drawing Tests will be compared to the algorithm
scores. Scoring algorithms for the ROCFT and the Clock Drawing Test are applied post-data
collection. The scores estimated by the algorithms will be compared with manual scoring by a sample
of well-trained raters (n = 6; aim 2). The algorithms have been developed by Philips Research and
after positive comparison to the manual scores will be part of future releases of the ISO product. By
comparing the manual and algorithm scoring, we can investigate the agreement between the two for
the tests on the platform. This will be done by computing the relative inter-rater agreement (also
known as inter-rater reliability) between the algorithm and expert raters. Relative inter-rater agreement
implies that the algorithm ranks examinees the same as expert raters (n = 6).
6.3 Subjects
We have specified a Sampling plan that ensures representativeness for the US population in Appendix
A. The sampling plan establishes initial normative reference ranges, provides psychometric evaluation
of retest reliability, and provides a direct validation of digital scores relative to paper-and-pencil scores.
Furthermore, this protocol establishes that older adults coming from a variety of backgrounds
consistent with the general population of the United States can adequately follow the test
administration rules with minimal proctoring, understand how to interact with the iPad to successfully
enter his/her response to items, and a sufficient behavioral sample can be collected to establish
reference ranges.
Inclusion criteria for subject selection
•
Examinee’s primary language (language most often spoken) must be English.
•
If examinee has vision impairment or hearing loss, must be corrected to normal.
•
Must have normal fine and gross motor ability
•
Must have use of fingers, hands, and arms to be able to use a pencil to write symbols.
Must be able to understand subtest instructions and participate fully in testing
Exclusion criteria for subject selection
•
Evidence of current cognitive impairment
•
Disruptive behavior or insufficient compliance with testing to ensure a valid assessment.
•
Examinee must not be currently admitted to a hospital, assisted living, nursing home or a
psychiatric facility.
•
Examinee must not be diagnosed with a neurological disorder or disease (e.g., Parkinson’s, brain
tumor, stroke, TBI, epilepsy [if # seizures
2 and not receiving ongoing treatment for seizures,
and not currently seeking medical evaluation or attention related to seizures, examinee can be
accepted], encephalitis, dementia, language disorder (expressive or mixed receptive/expressive
excluded; articulation disorder is ok), learning disorder
•
Must not have been unconscious related to traumatic brain injury or “medical condition” > 20
minutes (however, e.g., heat stroke, medication induced are Ok) or any head-injury resulting in an
overnight hospital stay
•
Any history of a medical event requiring resuscitation in which examinee was non-responsive for>
15 minutes.
•
Must not have current or recent functional change (ability to carry out usual duties at work, in
school, IADLs [driving, shopping, managing money], etc.) due to cognitive change.
•
Exam inee must not be receiving chemotherapy treatment, or have received chemotherapy
treatment in the past 2 months.
•
Examinee must not have a history of ECT or radiation to the CNS.
•
Examinee must not be (currently or in the past) diagnosed with a psychotic disorder, or currently
diagnosed with a mood disorder (however, Major Depressive Disorder in remission or with no
Title: Clinical Investigation Plan
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Version: 2.0
Date: 2019-02-18
Status: Approved
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current episode, and Dysthymic and Adjustment Disorders, are acceptable) or an anxiety disorder
with symptoms significant enough to interfere with optimal test performance.
•
Autoimmune disorder (e.g., LUPUS, Multiple Sclerosis)
•
Examinee must not be currently diagnosed with substance abuse or dependence, or have carried
any substance abuse or dependence diagnosis in the past year (> 1 year in remission diagnoses
are Ok). Long term alcohol abusers are excluded as well (e.g., abused substance for more than 10
years)
•
Any history of Autism Spectrum Disorder or Intellectual Disability.
•
The examinee must not be currently taking medication that might impact test performance (e.g.,
anti-convulsants, antipsychotics, benzodiazepines, psychostimulants, opiods, tricyclic
antidepressants, some norepinephrine reuptake inhibitors). Most antihypertensive medications
and statins are acceptable.
•
If previously diagnosed with any physical condition or illness that might depress test performance,
illness must not interfere with normal cognitive functioning at work, school, ADLs, etc. Diabetes,
hypothyroidism, and hypertension are acceptable if controlled.
•
Exclude primarily nonverbal or uncommunicative. Must not have a diagnosis of aphasia.
•
Examinees should not have received neuropsychological testing although previous MMSE testing
is allowed if more than 6 months prior
•
Examinee must not be seeking medical diagnostic procedures for cognitive difficulties from a
medical professional.
•
Non-valid health insurance in USA.
Criteria and procedures for subject withdrawal or discontinuation
Subjects will be enrolled when the inclusion criteria and exclusion criteria are met and when the
subject has signed the informed consent form.
Subjects can leave the study at any time for any reason if they wish to do so without any
consequences.
If one of the following criteria is fulfilled, the participation of a subject to the study is terminated:
•
Subject indicates that he wishes to leave the study
•
Subject is not able to use the iPad Pro (test data will not be destroyed but flagged as invalid)
•
Subject does not meet inclusion/exclusion criteria anymore
•
The investigator can decide to withdraw a subject from the study for medical reasons.
These subjects need to be replaced according to the sampling plan if test data of a subject are
destroyed or test data are not complete due to study termination.
The point of enrolment is the time at which, following recruitment, a subject signs and dates the
informed consent form. The first subject is expected to be enrolled in March 152019. The Clinical
Investigation is expected to take 6 months.
The duration of each assessment is 90 minutes.
In this clinical investigation, the company that will recruit the participants will account for an expected
dropout rate of 20%.
6.4 Procedures
Specimen Banking (saving human fluid or tissue for future research)
Not applicable—this is a human study without specimen banking.
Clinical procedures
Participants included in group A-D will be invited for an assessment on two different time points
(phases). Both assessments will take approximately 1.5 hours. After signing an informed consent,
participants will receive either all digital or all paper-pencil cognitive tests in phase 1 and either all
digital or all paper-pencil cognitive tests in phase 2, depending on group assignment. See figure 1 for
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an overview of the study design. Participants included in group E of the study (see figure 1) will only
receive one assessment (all digital cognitive tests). 50% of group E will be enrolled in phase I and the
other 50% of group E will be enrolled in phase 2.
This assessment will take approximately 1.5 hours. All participants will be asked to complete a MoCA
screener. The study will be concluded when each cell of the design (group A-E) meets its required
sample size with participants that meet the inclusion criteria and completed the tests specified for their
group.
Sponsor activities
Philips, as the sponsor, will be responsible for:
•
Internal Ethics approval
•
Providing Principal Investigator
•
Study Design
•
Monitoring
•
Data storage
•
Data integrity check
•
Data analysis
•
Report
Supplier (CRC activities):
•
Selection of rooms for data collection
•
Selection of psychometrists
•
IRB approval
•
Recruitment of participants
•
Data collection
6.5
Monitoring plan
In accordance with 21 CFR 312.56, the clinical monitor will periodically inspect all CRFs, study
documents and research facilities associated with this study at mutually convenient times during and
after completion of the study. As required by FDA regulations (Responsibilities of Sponsors and
Investigators), the monitoring visits provide the Sponsor with the opportunity to evaluate the progress
of the study; verify the accuracy and completeness of CRFs; ensure that all protocol requirements,
applicable FDA regulations, and investigator’s obligations are being fulfilled; and resolve any
inconsistencies in the study records. This includes inspection of all documents and records that are
required to be maintained by the investigator.. The names and identities of all research subjects will be
kept in strict confidence and will not appear on CRFs or other records provided to or retained by the
Sponsor. The regulations also require the investigator to allow authorized representatives of the FDA
to inspect and make copies of the same records. The names and identities of the subjects need not be
divulged to the Sponsor; however, the records must nevertheless be inspected. This can be
accomplished by blacking out the subject’s name and replacing the name with the subject’s study ID
number. If these requirements are in conflict with local regulatory restrictions or institutional
requirements, the investigator must inform the Sponsor of these restrictions prior to initiation of the
study.
See the Monitoring Plan for a description of how monitoring of the conduct and progress of the clinical
study will be conducted. Monitoring of the study will be conducted by Philips according to the
monitoring plan (CT1 8_Monitoring_Plan).
7 STATISTICAL CONSIDERATIONS
Statistical design, analyses and power considerations
Below we describe the planned analyses for each aim and hypothesis. The tests are scored by two
raters (with 30% overlap) and inter-rater agreement is assessed prior to proceeding with the following
analyses. All correlations mentioned below are Pearson correlations. Retest correlations are corrected
for the variability of the normative sample (Allen & Yen, 2002; Magnusson, 1967). Correlation between
paper and pencil measures are corrected for measurement error (Padilla & Veprinsky, 2012). In our
power analyses we assume an alpha of .05.
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Aim I comparison of psychometrics.
Hypothesis A: Digital and paper-pencil test scores are comparable.
For each test, we will first compute age-only referenced scores for digital and paper-pencil version
separately. Referenced scores are computed based on the regression based norms (procedure
described below under aim 3) and are represented as z-scores indicating a participant’s deviation from
what would be expected based on the norm sample for a participant with identical demographic
characteristics. We then compute the correlation between digital and paper-pencil referenced scores
within participants in group A and B (which are the groups in which participants completed both digital
and paper-pencil versions of the tests), which needs to be r> .6 to be considered comparable. Our
planned sample size allows us to detect a correlation of r> .2 with 80% power. We also perform an
equivalence test for each test, comparing the distribution of digital normed scores with paper-pencil
normed scores, using a two-one-sided-t-test approach (TOST; Schuirmann, 1987), with equivalence
bounds of ± .3 sd, which we have 99% power to detect. Our planned sample size would allow us to
detect equivalence with bounds of at least ± .21 with 80% power.
Hypothesis B: Test-retest reliability is comparable.
Test-retest reliability will be tested by examining for each test the correlation between the digital tests
in phase 1 and phase 2 (group C) and comparing this to the correlation between the paper-pencil tests
in phase 1 and phase 2 (group D). High test-retest correlations are expected (r> 0.7), except for the
ROCFT copy condition, since the scores of this condition generally show a moderate ceiling effect.
The planned sample size for group C and group D each yield 80% power to detect r> .37.
Hypothesis C: Construct validity is comparable.
Construct validity will be investigated by means of two confirmatory factor analyses (CFA), one for
each group (digital vs. paper-pencil). We expect to see that the factor structure that fits the paper-
pencil data (phase 1, group B & D) well, will also fit the digital data (phase 1, group A & C) well.
Assuming that at most two variables per test are included in the CFA, the subject-to-variable ratio is
near 10:1 for each CFA.
Aim 2 Agreement between algorithm and manual scoring
Hypothesis D: The score(s) provided by the ROCFT and Clock Drawing Test scoring algorithms on
ISC are correlated highly (> .8) to the score provided by manual scoring for the same drawings.
For each test with algorithmic scoring, agreement with manual scoring will be tested using the two-
one-sided t-tests approach (TOST; Schuirmann, 1987) on the average correlation between the
algorithm and each rater on the one hand and the average correlation between the rater and each
other rater on the other. Before submitting the correlations to the TOST analysis, we apply Fisher’s r
to-z transformation. We will use equivalence bounds of r ± .1 as a stringent criterion of practical
equivalence, although we note that any correlation > .8 provides sufficient support for our claim given
that the algorithms may actually be more an improvement relative to manual scoring.
We used a simulation approach to estimate the sample size of raters needed to have 80% power to
detect equivalence in agreement using TOST. This approach is described in detail in Technical Note
PR-TN2018/0033 (Dotsch & Klaming, 2018). For the ROCFT, the simulation approach has resulted in
the recommendation that six raters will be required to score a random sample of 100 drawings from
the test in order to derive at least 80% power with stringent equivalence bounds backing a strong
claim of equivalence between raters and algorithm. We assumed that for the CDT a similar number of
raters would be sufficient, given that scoring of drawings from both tests have generally high inter-rater
agreement.
Aim 3. Estimate regression-based norms and reliable change indices
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The data collected can be used to establish regression-based norms. 250 (up to 300) participants
(group A&C, phase 1 and group E) will be included in the norm group. These norms can be used for
the IntelliSpace Cognition tool and may be updated at a later point in time.
Reference scores (for age, educational level, gender, and ethnicity) will be generated using linear
regression techniques. We will additionally estimate regression based reliable change indices.
Aim 4. Estimate factor loadings for cognitive model describing
We have developed a model of cognitive functioning using the latent variable part of structural
equation modelling (which is identical to the CFA described above). We will fit the ISC model of
cognitive functioning on the digital test data from Group A, C, and E, yielding a sample of 250 (up to
300) participants for the CFA, further increasing the subject-to-variable ratio to —12:1.
Sample size
The study will include a total of N = 400 (up to N450) healthy individuals, without accounting for drop
out (see Figure 1 for the design); The tests will be scored by two well-trained raters. Moreover, to
compute the inter-rater agreement between scoring algorithms and manual scoring we need six
additional well-trained raters.
Significance and power
Please see above description.
Expected drop-out rates
The expected drop-out rate is 20%. The company that will recruit the participants will oversample by
20% to account for the drop-out rate, resulting in 80 additional participants recruited in addition to the
400 needed for the full design.
Passlfail criteria
Please see above description.
Interim analysis
Not applicable.
Termination of entire study on statistical grounds
The study will be terminated if a sample size of N = 400 with the specified distribution across age,
gender, education level, and ethnicity cannot be achieved.
8 DATA MANAGEMENT
Data will either be captured on paper and later transcribed to the electronic case report forms (eCRF5)
or directly reported into the eCRFs at the time of procedure completion. Digital test data will be
captured with our digital software tools in the cloud. Ultimately, Philips will handle all data in the
Datatrak system.
Researchers will be trained on the devices and the specific data management for the study prior to the
start of the study. The researchers will be provided usernames and passwords unique to each
researcher.
Paper source documentation (firstly documenting data on paper with later transcription into the
eCRFs) shall be used for data metrics (e.g., informed consent, randomization, safety metrics captured
elsewhere, eligibility metrics, standard Site forms, etc.).
Documents that may be used to capture source data on paper include, but are not limited to: standard
Site forms, study diaries, or any of the Document Template forms, etc. Each paper form shall have
adequate study/Site and subject identifiers and must be and remain legible. A blue or black pen
should be used to document data. A pencil should never be used.
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Researchers will be provided with the required forms by Philips, a paper template of the fields required
to complete the eCRF. These will allow researchers to identify which data points will require
documentation across the study.
Procedures
1.
The supplier will have a compliant procedure to assure the data collection is collected according
the regulations and that the data is stored and cannot be altered.
2.
The data will be collected by Supplier and gathered by Philips after completion.
3.
Digital data will be stored in the (Philips) cloud which is HIPAA and part 11 compliant.
4.
Data will be reviewed and cleaned by Philips.
5.
Philips will handle all data in the Datatrak system.
All systems that are being used are CFR part 11 compliant.
Data retention
Please see PlAsupport document for a detailed overview of data collected and their retention time.
All records and documents pertaining to the study including, but not limited to, data and source
documents, will be maintained by the sponsor for a period of 15 years. In order to avoid any possible
errors, the researcher will contact the Sponsor prior to the destruction of any study records. The
researchers will promptly notify the Sponsor in the event of accidental loss or destruction of any study
records.
However the digital data generated by the study will be used as part of the ISO product as the ground
norm data set of the device (see study objectives). These records will not be related to any patient ID,
but will be delivered as part of the ISC product to future customers once the product is on the market.
Quality Assurance
The Sponsor or its designee will implement steps to maintain quality control (QC) and quality
assurance (QA) to ensure that the study is conducted and data are generated, documented, and
reported in compliance with the protocol, good clinical practice, and applicable regulatory
requirements. This will be completed by Sponsor monitoring visits.
Regular monitoring and an independent audit, if conducted, must be performed according to ICH
GCP. QC procedures will be implemented beginning the study data QC checks will be performed. Any
missing data or data anomalies will be communicated to the researchers for clarification/resolution. It
is the responsibility of the researcher to respond to all edits checks and queries. Stored data as well as
all data modifications to stored data will be documented by the system and available in audit trails.
Following written procedures, the monitors will verify that the clinical trial is conducted and data are
generated, recorded, and reported in compliance with the protocol, GOP, and the applicable regulatory
requirements.
The researchers will provide direct access to all trial related sites, source data/documents, and reports
for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory
authorities. In addition, post data submission, Philips (or contracted) Monitors, Project Statistician,
and/or the Data Management group will remotely review data generated at different time points during
the study. Data queries will be generated to resolve any discrepancies or concerns.
9 AMENDMENTS
Any changes to the clinical study protocol after initial lOBE approval are documented as protocol
amendments. After lOBE approval, and prior to execution at the study site, the amendment will be:
•
submitted and approved by the applicable IRB
•
signed by the Investigator(s)
10 DEVIATIONS
Protocol deviations are any alteration or deviation from the lOBE-approved research plan as defined in
the study protocol. This includes equipment failures during study procedures. The researcher will
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deviate from the protocol whenever necessary to protect the participant’s health, rights or welfare and
these types of deviations will be reported to ICBE and the external IRB as soon as possible. Major
deviations must be reported to ICBE and the IRB as soon as possible.
In non-urgent/emergent
situations, the researcher will obtain ICBE-approval for the planned deviation in advance of performing
the changed activity.
If the researcher anticipates that there will be future requests for the same deviation, then the protocol
will be amended (and such amendments must be approved by ICBE and the IRB). A minor deviation
is something that does not cause harm or have the potential to cause harm to the participant, and
does not impact the integrity of the study. These shall be documented in the study file and uploaded
to ICBE for their awareness. Other reasons for amendment requests include adding a study site,
increasing the number of research participants, and extending the time to perform the study. If the
study objectives and procedure or cohort changes or the study changes from non-medical to medical,
this generates a new study (not an amendment).
Corrective and preventive actions and principal disqualification criteria
When necessary, there will be given additional training to the researchers to conduct the study
according to protocol.
11 DEVICE ACCOUNTABILITY
The procedures for the accountability of investigational devices are in accordance with the Guidance.
The access to investigational devices will be controlled and the investigational devices will only be
used in the clinical investigation and according to the CIP.
The sponsor shall keep records to document the physical location of all investigational devices from
shipment of investigational devices to the investigation sites until return or disposal. This record will be
based on Validation ISO
— device list.
The principal investigator or an authorized designee shall keep records documenting the receipt, use,
return and disposal of the investigational devices. This is all documented in the Validation ISO
—
device list. This record shall include (if applicable):
•
the date of receipt,
•
identification of each investigational device (batch number/serial number or unique code),
•
the expiry date, if applicable,
•
the date or dates of use,
•
subject identification,
•
ate on which the investigational device was returned/explanted from subject, if applicable, and
•
the date of return of unused, expired or malfunctioning investigational devices, if applicable.
12 STATEMENTS OF COMPLIANCE
The clinical investigation will be conducted according to the principles of the Declaration of Helsinki
and other guidelines, regulations and Acts.
The clinical investigation shall not begin until the required approval/favorable opinion from lOBE and
the IRB have been obtained. Any additional requirements imposed by lOBE and the IRB shall be
followed.
Compensation for injury
General liability insurance is arranged by Royal Philips.
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Sponsor wishes to obtain dispensation from statutory obligation to provide insurance, because
participating in the study is without risks. A reasoned request will be made to accredited EC and this
dispensation will be mentioned here.
13 INFORMED CONSENT PROCESS
Select all that apply:
The requirement for informed consent has been waived (i.e., not required
by law OR waived by IRB/REC/METC). Upload waiver if available.
Written informed consent will be obtained from adult participants
Assent will be obtained from children/minors
Parental permission will be obtained when children are participating
Surrogate consent will be obtained when participants lack decisional
capacity
Deferred consent will be obtained [e.g., emergency research]
D Click-through consent will be obtained [Internet/app-based research]
Implied consent [i.e., consent through action such as taking a test]
13.1
Consent Process (See Section 13.3 re Assent & Permission)
Study participation is voluntary. Potential subjects, are given the most current ICBE/IRB approved
consent form to read. They will be provided ample time (+1 week) for review and an opportunity to ask
questions about the study. The informed consent form will be provided by the CRC during the
recruitment process. If they agree to participate, the CRC will schedule the participant for
participantion and they will sign the consent form before the start of the study. They will be given a
copy of the signed document for their records. Each of these actions/steps will be documented. Only
after Informed Consent has been obtained, may the remaining study procedures begin.
13.2
New Information about the Study
Any new information about the study that may affect a consented subject’s decision to be in the study
(e.g., changed procedures, safety, etc.), will be communicated in a timely manner. Depending on the
nature of the new information, subjects who have completed the study may or may not be informed,
documenting the decision and justification as well as any activities for informing completed subjects.
Additionally, the approving IRB will also be informed. The currently approved Consent Form will be
updated and submitted to the ICBE and approving IRB for review and approval. Active subjects will be
re-consented, following the above process, with the newly-approved consent form.
13.3
Inability to Provide Consent (children or adults)
N/A
14 ADVERSE EVENTS AND DEVICE DEFICIENCIES
Definitions
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Adverse events and adverse device effects, device deficiencies and serious adverse events and
serious adverse effects and, unanticipated serious adverse device effects are defined in the table
below:
Definition
Description
Adverse Event
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs
(AE)
(including abnormal laboratory findings) in subjects, users or other persons, whether or not
related to the investigational medical device
NOTE 1 This definition includes events related to the investigational medical device or the
comparator.
NOTE 2 This definition includes events related to the procedures involved.
NOTE 3 For users or other persons, this definition is restricted to events related to
investigational medical devices.
Adverse
Adverse event related to the use of an investigational medical device
Device Effect
NOTE 1 This definition includes events related to the investigational medical device or the
“
comparator.
NOTE 2 This definition includes events related to the procedures involved.
NOTE 3 For users or other persons, this definition is restricted to events related to
investigational medical devices.
Serious
Adverse event that
Adverse Event
a) led to death,
‘SAE’
b) led to serious deterioration in the health of the subject, that either resulted in
‘
‘
1) a life-threatening illness or injury, or
2) a permanent impairment of a body structure or a body function, or
3) in-patient or prolonged hospitalization, or
4) medical or surgical intervention to prevent life-threatening illness or injury or
permanent impairment to a body structure or a body function,
c) led to foetal distress, foetal death or a congenital abnormality or birth defect
NOTE Planned hospitalization for a pre-existing condition, or a procedure required by the
CIP, without serious
deterioration in health, is not considered a serious adverse event.
Serious
Adverse device effect that has resulted in any of the consequences characteristic of a
Adverse
serious adverse event or that might have led to any of these consequences if suitable action
Device Effect
had not been taken or intervention had not been made or if circumstances had been less
(SADE)
Unanticipated
.
.
.
.
Serious adverse device effect which by its nature, incidence, severity or outcome has not
Adverse Device
been identified in the current version of the risk analysis report
NOTE Anticipated serious adverse device effect (ASADE) is an effect which by its nature,
incidence, severity or outcome has been identified in the risk analysis report.
Reportability
All adverse events shall be reported to the Study Manager. ADEs, SAEs, SADEs and USADEs shall
be reported to the Q&R office as well. The Director Q&R shall assess the ADEs, SAEs, SADEs and
USADEs for reportability to Competent Authorities.
Reporting process
Reporting shall include the date of the adverse event, research subject ID#, description of the adverse
event, treatment, resolution, and assessment of both the seriousness and the relationship to the
investigational device and study procedures.
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Timelines
The time period in which the principal investigator shall report all adverse events and device
deficiencies to the sponsor and, where appropriate, to ECs and the regulatory authority, and the
details of the process for reporting device deficiencies, are detailed in the table below.
Category
Report to Study Manager
Report to Accredited Ethics
Report to Q&R office
Committee
by
by
by
Principal Investigator
Principal Investigator
Principal Investigator
by Study Manager
Adverse Event
Periodic reporting to
As part of Sponsor’s Clinical Investigation Report
(AE)
Sponsor
Periodic collection by
Sponsor
Adverse Device
As part of Ethics Committee
Effect (ADE)
Reporting timelines
or
<24 hrfollowing instructions by
Sponsor
Serious Adverse
As part of Ethics Committee
Event
Reporting timelines
(SAE)
Immediate, <24 hr
or
Immediate, <24 hr
<24 hrfollowing instructions by
Sponsor
Serious Adverse
Immediate, <48 hrs
Device Effect
(SADE)
Unanticipated
As part of Ethics Committee
Adverse Device
Reporting timelines
Effect (UADE)
or
<24 hr following instructions by
Sponsor
Foreseeable adverse events and anticipated adverse device effects
No adverse events and anticipated adverse device effects are foreseen. The only event we foresee is
fatigue of participants that are participating in our study.
Since there are no possible adverse events, there is no foreseen need to contact the IRB
Device malfunction will be reported to the sponsor directly who then needs to take a decision to
stop/suspend or continue the trial depending the software fault and the risks of achieving the trial
objectives. There is no risk for the subjects even if the device is at fault.
Emergency contact details
N/A
Information regarding the Data Management Committee, if established
N/A
Incidental Finding Reporting
An Incidental Finding is a finding concerning an individual research participant that has potential
health or reproductive importance and is discovered in the course of conducting research but is
beyond the aims of the study.
All incidental findings will be documented in a timely manner throughout the study. The report
Incidental Finding Report Form (see lOBE SP) will be in the receipt of Philips Research Q&R Office
within 7 business days of when the researcher first learns about the finding.
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15 INVESTIGATOR BROCHURE (IB)
An lB is needed and included in the lOBE study dossier.
16 VULNERABLE POPULATION
According to ISO 14155, a vulnerable subject is an individual whose willingness to volunteer in a
clinical study could be unduly influenced by the expectation, whether justified or not, of benefits
associated with participation or of retaliatory response from senior members of a hierarchy in case of
refusal to participate.
None—this study uses live human participants but not from vulnerable populations
Indicate whether you will include any of the following (vulnerable) populations in your study:
Children or viable neonate (birth to age 28 days)
Cognitively impaired
L Pregnant women (except USA)
D Fetuses
Neonates of uncertain viability or nonviable
fl Prisoners
E Poor/uninsured
Educationally disadvantaged (limited education, e.g., high school drop out)
Students (including interns, residents, fellows)
L Minorities (includes migrants, refugees)
Elderly (over age 65 years)
L Terminally ill
D Other (check box and specifically discuss below)
Informed consent form will be provided with detailed information about the study.
Psychometrists who are experienced with this age group will collect the data.
17 SUSPENSION OR PREMATURE TERMINATION
In case the study is ended prematurely, the investigator will notify the IRB and the ICBE about the
reasons for the premature termination.
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The principal investigator or authorized designee shall inform the subjects of the reasons for
resumption.
The following criteria and arrangements for suspension or premature termination of the whole clinical
investigation or of the clinical investigation in one or more investigation sites apply:
•
Philips decides to stop the study.
In case of suspension or premature termination of the clinical investigation, the following requirements
apply for subject follow-up.
•
N/A
18 PUBLICATION POLICY
Results of clinical investigation may be submitted for publication. Philips shall register and report the
results of this applicable trial on clinicaltrials.gov.
19 BIBLIOGRAPHY
List of bibliographic references pertaining to clinical investigation
Allen, M. J., & Yen, W. M. (2002). Introduction to measurement theory. Long Grove, IL: Waveland
Press.
Akshoomoff, N. A., & Stiles, J. (1995). Developmental trends in visuospatial analysis and planning:
memory for a complex figure. Neuropsychology, 9(3), 378-389.
Anderson, P., Anderson, V., & Garth, J. (2001). Assessment and development of organizational ability:
the Rey Complex Figure Organizational Strategy Score (RCF-OSS). The Clinical Neuropsychologist,
15(1), 81-94.
Bauer, R.M., Iverson, G.L., Cernich, A.N., Binder, L.M., Ruff, R.M., & Naugle, R.I. (2012).
Computerized neuropsychological assessment devices: joint position paper of the American Academy
of Clinical Neuropsychology and the National Academy of Neuropsychology. Archives of Clinical
Neuropsychology, 27, 362-373.
Bennett-Levy, J. (1984). Determinants of performance on the Rey-Osterrieth Complex Figure Test: an
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Jenike, M. A.
(2000). Reliability and validity of a scoring system for measuring organizational approach in the
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Taylor Complex Figure Tests: a new scoring system. Psychological Assessment, 5(1), 27-33.
Title: Clinical Investigation Plan
Author: Laura Kiaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
Page: 34 of 35
IRBMANAGER PILOT —01 PROJECT

Philips Research
P1—I I LI PS
Kiaming, L., & Vlaskamp, B.N.S. (2017). Non-dominant hand use increases completion time on part B
of the Trail Making Test but not on part A. Behavior Research Methods, 1-14.
Magnusson, D. (1967). Test theory. Reading, MA: Addison-Wesley.
The MarkeTech group (2018). An online survey of 75 US-based neurologists, conducted by The
MarkeTech Group.
Miller, J.B., & Barr, W.B. (2017). The technology crisis in neuropsychology. Archives of Clinical
Neuropsychology, 1-14.
Padilla, M. A., & Veprinsky, A. (2012). Correlation Attenuation Due to Measurement Error: A New
Approach Using the Bootstrap Procedure. Educational and Psychological Measurement, 72(5),
827—846. https://doi .org/10.1177/0013164412443963
Paolo, A.M., Axeirod, B.N., & Ryan, J.J. (1994). Administration accuracy of the Wisconsin Card
Sorting Test. The Clinical Neuropsychologist, 8(1), 112-116.
Schatz, P., & Browndyke, J. (2002). Applications of computer-based neuropsychological assessment.
The Journal of Head Trauma Rehabilitation, 17(5), 395-410.
Shorr, J., Delis, D., & Massman, P. (1992). Memory for the Rey-Osterrieth Figure: perceptual
clustering, encoding, and storage. Neuropsychology, 6, 43-50.
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administration, norms, and commentary (3rd ed.). New York: Oxford University Press.
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Computerized Wisconsin Card Sorting Test: comparison with manual administration. Kaohsiung
Journal of Medical Sciences, 12, 479-485.
An online survey of 75 US-based neurologists, conducted by MarkTech Group, revealed that
the average waiting time for a neuropsychological evaluation is 7.6 weeks.
5 75 US-based neurologists were asked; “For what percentage of all your patients do you
currently request a full neuropsychological assessment?” The average of all responses was
13%. They were then asked, “In an ideal world which percentage of all your patients would
you like to send for a full neuropsychological assessment?” The average of all responses
was 36%.
[End of document]
Title: Clinical Investigation Plan
Author: Laura Klaming
Company Restricted
DodD: ICBE-2-28674
Version: 2.0
Date: 2019-02-18
Status: Approved
Page: 35 of 35
IRBMANAGER PILOT —01 PROJECT

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White
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Hispanic
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> 12 years
50-54
50
25
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33
7
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15
30
55-59
50
25
25
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6
6
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16
29
60-64
50
25
25
36
6
5
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16
29
65-69
50
25
25
37
5
5
3
5
15
30
70-74
50
25
25
37
6
5
2
6
15
29
75-80
50
25
25
40
4
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9
18
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