Assessing the Malleability of Spatial Abilities in Individuals With Down Syndrome
Phase: NA
Conditions: Down Syndrome
Sponsor: University of Alabama, Tuscaloosa

ASSESSING THE MALLEABILITY OF SPATIAL ABILITIES IN INDIVIDUALS WITH DOWN SYNDROME 
NCT05332912 
Initial IRB Approval: 9.19.2019 
Lastest IRB Approval: 8.08.2024 
 
PROTOCOL AND DATA ANALYSIS PLAN 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
PROTOCOL
IRB Form
University of Alabama
Protocol # 19-08-2644
 Date Printed:
09/17/2025
Continuing Review
1
Personnel Information
6
Subject Population
8
Study Location
9
General Checklist
9
Funding
10
Expedited Review
10
Background , Purpose , Study Procedures
12
Radioisotopes or Radiation Machines
18
Drugs, Reagents, Chemicals, or Biologic Products
19
Devices
19
Subject Population(a-h)
19
Subject Population(i-l)
20
Subject Population(m)
21
Subject Population(n)
25
Subject Population(p)
30
Risks
33
Benefits/Alternatives, Procedures to Maintain Confidentiality
34
 Potential Conflict of Interest
36
Informed Consent
38

 
PROTOCOL
IRB Form
University of Alabama
Protocol # 19-08-2644
 Date Printed:
09/17/2025
Assent
38
HIPAA
39
Attachments
40
PI Obligations
42
Event History
43

Page 1 of 47
 
1
PROTOCOL
IRB Form
University of Alabama
Protocol # 19-08-2644
 Date Printed: 09/17/2025
-------------------------------------------------------------------------------------
Protocol Title:
Assessing the Malleability of Spatial Abilities in Individuals
with Down Syndrome
Protocol Status:
APPROVED
Date Submitted:
07/15/2024
Approval Period:
08/08/2024-01/01/2050
Important Note:
This Print View may not reflect all comments and contingencies for approval.
Please check the comments section of the online protocol.
Questions that appear to not have been answered may not have been required
for this submission. Please see the system application for more details.
* * * Continuing Review * * *
 
Continuing Review/Annual Report
 
WHAT TO UPLOAD WITH YOUR CONTINUING REVIEW APPLICATION
 
 
      
 
   
For studies where research activities are limited to data analysis, upload participant
safety information and publications (e.g., manuscripts, abstracts) since the last IRB
approval, if applicable.
 
      
 
   
For all other studies, upload:
â€¢ A clean (unstamped) copy of consent/assent document(s) to be stamped
upon IRB approval.
â€¢ Participant safety information including the most current Summary of all
serious adverse events and unanticipated problems involving NSKS to
participants or other and data safety monitoring reports since the last IRB
approval, if applicable.
Any publications (e.g., manuscripts, abstracts) since the last IRB approval.
 
      
 
   
Any changes, updated and/or new study materials should be uploaded and
questions 19 - 24 of this form should be completed.
 
 
   
  1. Please indicate the status of the study:
a)
The study has not started but will become active.
     
   
   
Please explain why the study has not started.
b)
X
The study is ACTIVE (please check the appropriate box below):
Study is open to accrual.
Study is on hold or halted.

Page 2 of 47
 
        
      
      
Please explain what needs to occur before accrual can resume:
X
Study is permanently closed to accrual.
 
i.  
Y
Have all participants completed all research related
activities/interventions?
ii.  
N/A Will the research only remain active for long-term follow-
up of participants?
iii.  Y
Are remaining research activities limited to data analysis
only?
 
 
      For IRB office use: * may qualify for expedited review
 
c)
The study has expired and needs to be re-initiated.
Explain any research activities occurring during lapse in IRB approval.
 
   
  2. Date the study was initially approved by the IRB:
09/19/2019
 
   
  3. Approval date of previous continuing review:
09/27/2023
 
   
  4. Total number of participants/records/specimens approved to
date.
102 (54 Children and
48 Down syndrome)
 
   
  5. Total number of participants that have given consent (verbal
or written) to date.
54 children and 30
Down Syndrome
 
   
  6. Total number of participants that failed  screening(if not
applicable, state N/A).
N/A
 
   
  7. Total number of participants accrued since the beginning of
the project.
84
 
   
  8. For multi-center studies, number of participants approved for
accrual study-wide (University of Alabama site plus all other
sites).
102
 
   
  9. 
 
For multi-center studies, number of participants enrolled
study-wide (University of Alabama site plus other sites).
84
 
    
10. 
    
Number of withdrawals from the research (since last approval date) and
explanation/reasons for withdrawals.
0
 
    
11. 
    
Description and number of:

Page 3 of 47
 
 
      
      
  
  
a)  Reportable Protocol Deviations/Violations since the last approval date:
0
 
      
      
  
  
b)  Serious Adverse Events (SAEs) or unanticipated problems involving risks to
participant or others since the last approval date:
0
  12.  Have there been any complaints about the research during the last year?
N
             If yes, please describe.
 
    
13.   Briefly describe the progress of the study to date.
Data collection has been completed. Anaysis is underway.
 
    
14.   Is there a Data Safety Monitoring (DSM) plan for this study?
X
No
Yes, a copy of the DSM report(s) for the last approval period is attached.
Yes, but a copy of the DSM report(s) for the last approval period is not
attached. Please explain below.
 
    
15.  
FDA Regulated Studies
 
          
     
Is this a Food and Drug Administration (FDA) Regulated Study, (i.e.,
involves drugs, devices, biologics)? If yes, please answer the following
questions:
N
 
a)
Have there been any changes in the FDA status
of any drug or device used in the study?
         
     
      
  
    
If yes, please explain:
 
b)
Have any of the investigational drugs or devices
used in this study received FDA approval?
         
     
      
  
    
If yes, please explain:
 
c)
Have any new alternative drugs or devices been
approved for treatment of the study condition that
may affect participants willingness to participate?

Page 4 of 47
 
         
     
      
  
    
If yes, please explain:
 
         
     
      
  
    
Have current participants been notified? Please explain:
 
d)
Has there been a change in the standard care
that may be considered as an alternative to the
investigational drug or device or that would affect
the original study design?
         
     
      
  
    
If yes, please explain:
 
         
     
      
  
    
Have current participants been notified? Please explain:
 
e)
Is there any new information that might affect the
risk/benefit ratio and the willingness of current
study participants to participate or to continue to
participate in the research?
         
     
      
  
    
If yes, please explain:
 
         
     
      
  
    
Have current participants been notified? Please explain:
 
f)
Is there any new information about study as a
whole, the drug, or device that needs to be
provided to past participants
         
     
      
  
    
If yes, please explain:
 
         
     
      
  
    
If no, please explain:
 
g)
Does the study include an investigator's brochure
(IB)?
      
      
   
  
  If yes, what is the current version date?
         
     
      
  
   
(If study has multiple IBs, attach current versions in Attachments section
(#15))
 
    
16.  
Provide a summary of any recent findings, literature, or other relevant information

Page 5 of 47
 
(especially pertaining to risks), if applicable.
N/A
 
 17.
Have there been any significant amendments or revisions
to the protocol that the IRB approved during the past
approval period? (Significant amendments include changes
in study design or risk level including those that resulted in
a change in consent).
N
  
     
If yes, please briefly summarize the changes:
 
   
18.
Are any changes (amendments) requested with this Continuing Review?
Y
Yes, please complete the remainder of this form.
No, form is complete. Please submit.
 
   
19.
Summarize the proposed changes to the protocol in lay terms including the type of
change AND  what the change involves.
Beverly Roskos, Alezandra Knapp, Ashley Kennedy, Karima Elgamal, Komal
Kehra, Melinda Mo, Crystal Infante, and Joselyn Angon-Martinez have left the
research program.
 
   
20.
Provide justification/explanation for the proposed changes.
Researchers graduated or left because testing of participants has been complete.
 
 21.
Will currently accrued participants need to be notified of
changes?
N
  
     
If No, please justify why not.
Not relevant to past participants.
  
     
If Yes, please explain how AND when notification or re-consenting will occur.
 
   
     
 
Proceed to the appropriate section(s) of the electronic application and make your changes.
Also make necessary changes in the protocol, Consent Form(s), Assent Form(s), Recruitment
Statement, Questionnaire or other attachments, if applicable. Upload any affected IRB
materials needing revision. Please provide the entire revised document (not just revised
pages). Use track changes in uploaded documents being revised. Please upload a clean copy
of each revised document to be stamped upon IRB approval.
 
NOTE: Protocol amendments must receive IRB review and approval before they are
implemented, unless an immediate change is necessary to eliminate an apparent hazard to
the participants.
 
Sponsored Studies: Remember to update the Sponsor's Protocol version number and date in
the Funding section of the protocol.

Page 6 of 47
 
 
Expedited Review
Attachments
---------------------------------------------------------------------------------------------
* * * Personnel Information * * *
Study Personnel Roles:
-Principal Investigator: accepts responsibility for study, can edit protocol, must submit to IRB
-Administrative Contact: additional study contact, can edit/prepare protocol, may or may not also be member of
research team
-Key Personnel (Research Team): University of Alabama member of research team, can view protocol (not edit)
-Non-Alabama Collaborator: member of research team from another institution or organization outside of
University of Alabama, has no access to system, must be provided with PDF of protocol.
-Department Chair: Official Department Chair, may or may not also be a member of research team, can view the
protocol (not edit). NOTE: a proxy may be listed if the Chair is the PI.
IMPORTANT NOTE: Human Participants Protection Training is mandatory for all research team personnel.
Principal Investigator  Mandatory
PI must be University of Alabama affiliate.
Name of Principal Investigator
(Faculty, Staff or Student)
Degree (MD/PhD/Other)
Title
Merrill, Edward
PhD
Professor Emeritus
Email
Phone
Fax
emerrill@ua.edu
+1 205 200 2183
Department Name
 
 
Psychology
 
 
Please indicate your status
Faculty
 
Is the (Role) also a Department Chair?
N
Human Subjects Training Completed?
Y
If you have completed training that is not auto-populated below, upload a copy in the
Attachments section.
Research Team Member Duties Picklist
1.
X Recruitment
2.
X Obtains consent
3.
X Determine participant Eligibility for
Accrual
4a.
Participant Physical Examinations
4b.
Follow-up Visits including physical
assessments
5.
Perform study procedures or
Specimen Collection
6a.
Administer and/or Dispense Study
Drugs, Biologics or Devices
6b.
Receive, Store, Manipulate or
Account for Study Drugs, Biologics
or Devices
7.
X Participant Randomization or Registry
8.
X Collection of Participant Data
9.
X Report Data (CRFs, e-CRFs,
Spreadsheets)
10.
X Data Analysis
11a. X Review Adverse Events
11b. X Treat and Classify Adverse Events
12.
Other (Please insert explanation below.)
 
 

Page 7 of 47
 
Course
CourseCompletionDat
e
CourseExpirationDate CourseID
Human Research
10/26/2008 5:53:42
PM
10/26/2010 5:53:42
PM
Medical Research
Human Research
5/8/2021 1:06:50 PM
5/7/2024 1:06:50 PM
Medical Research
CITI Conflicts of
Interest
7/1/2022 4:27:17 PM
6/30/2026 4:27:17 PM Conflicts of Interest
Human Research
7/1/2022 5:40:48 PM
6/30/2025 5:40:48 PM Non-Medical
Investigators
Human Research
7/16/2012 10:37:16
AM
7/16/2014 10:37:16
AM
Non-Medical
Investigators
Human Research
7/17/2019 10:02:41
AM
7/16/2022 10:02:41
AM
Non-Medical
Investigators
Responsible Conduct
of Research
7/29/2010 10:52:43
PM
7/29/2014
Biomedical
Responsible Conduct
of Research
Human Research
7/29/2010 11:33:27
PM
7/29/2013
Medical Research
CITI Conflicts of
Interest
7/5/2017 3:24:01 PM
7/4/2021 3:24:01 PM
Conflicts of Interest
Human Research
8/13/2014 9:47:52 PM 8/12/2016 9:47:52 PM Non-Medical
Investigators
Human Research
8/17/2016 2:10:40 PM 8/17/2019
Non-Medical
Investigators
 
 
 
Key Personnel (Research Team)
Name of Key
Personnel (Research
Team)
Degree
(MD/PhD/Other)
Title
Department Name
Bui, Chuong
Research Statistician Alabama Life
Research Institute
Conners, Frances
Professor
Psychology
 
Non - Alabama Collaborator
Name of Non -
Alabama
Collaborator
Degree
(MD/PhD/Other)
Title
Department Name
Yang, Yingying
PhD
Assistant Professor
A&S
Samantha
Zakrzewski
Undergraduate
Research Assistant
Other
Stephanie Grinshpun BA
Graduate Research
Assistant
Other
Matthew Baker
Undergraduate
Research Assistant
Other

Page 8 of 47
 
 
Department Chair  Mandatory
The official Department Chair should be listed here. If the Department Chair is the PI, a proxy
may be listed.
Name of Department Chair
Degree (MD/PhD/Other)
Title
Davis, Thompson
New Faculty-PA Not
Receive
Email
Phone
Fax
tedavis10@ua.edu
Department Name
 
 
Psychology
 
 
Human Subjects Training Completed?
Y
If you have completed training that is not auto-populated below, upload a copy in the
Attachments section.
Is Chair a member of the study team?
N
Research Team Member Duties Picklist
1.
Recruitment
2.
Obtains consent
3.
Determine Participant Eligibility for
Accrual
4a.
Participant Physical Examinations
4b.
Follow-up Visits including physical
assessments
5.
Perform study procedures or
Specimen Collection
6a.
Administer and/or Dispense Study
Drugs, Biologics or Devices
6b.
Receive, Store, Manipulate or
Account for Study Drugs, Biologics
or Devices
7.
Participant Randomization or Registry
8.
Collection of Participant Data
9.
Report Data (CRFs, e-CRFs,
Spreadsheets)
10.
Data Analysis
11a.
Review Adverse Events
11b.
Treat and Classify Adverse Events
12.
Other (Please insert explanation below.)
 
 
No training data is available.
 
---------------------------------------------------------------------------------------------
* * * Subject Population * * *
Subject Population(s) Checklist
Select All That Apply:
Adult Volunteers
X Cognitively Impaired Participants
Employees
Fetuses
X Minors (under 18)
Pregnant Women

Page 9 of 47
 
Prisoners
Students (Note: If students will be compensated extra-credit or course credit for participation in the research,
they must be given a non-research alternative for obtaining the same amount of credit, which is of
comparable time and effort as is required by the research activity.)
Terminally Ill Participants
Wards of the State (Note: Please consider whether the research population may also be considered
"prisoners" or "cognitively impaired." If so, please mark the appropriate corresponding categories in the
Subject Population Checklist)
Non-English Speakers (Note: Please provide copies of all correspondence that will be used as a part of the
research in English as well as in the native language of participants. Please also attach a copy of the
Translator's Declaration.)
Other (any population that is not specified above)
---------------------------------------------------------------------------------------------
* * * Study Location * * *
Study Location(s) Checklist
Indicate where the study will be conducted. Select all that apply:
X The University of Alabama
X Another University or College
Montclair State University,
NJ
VA Center
Hospital
X Other
Participant Home or
Locations Selected by
Parent
---------------------------------------------------------------------------------------------
* * * General Checklist * * *
General Checklist
Select All That Apply :
Study Eligible for Exempt Review
Non-human participants research
Collection of Specimens
Data collection via e-mail or the Internet
FDA Approved Device
FDA approved drugs, reagents, other chemicals administered to participants (even if they are not being
studied), or biologic products
Genetic Testing
HIV Testing
Human blood, cells, tissues, or body fluids
Investigational drugs, reagents, chemicals, or biologic products
Investigational Device
X Investigator Initiated Study
Medical Records
Photography, Video, or Voice-Recording Participants
X Questionnaires and/or tests
Radioisotopes/radiation-producing machines, even if standard of care
rDNA/Gene Transfer Therapy

Page 10 of 47
 
Registry or Repository Creation
Specimens to be stored for future research projects (must be in consent form)
Study of existing data or specimens
Other (clarify in text box to the right)
---------------------------------------------------------------------------------------------
* * * Funding * * *
Funding Checklist
NONE
 Funding - Grants/Contracts
Funding Type
Funded By
Government
National Institute of Health
NOTE: Applicable grant application, contract or subcontract, investigator's brochure, and
sponsor's protocol (for all industry sponsored clinical trials) must be attached. Click "Add" to
attach the documents.
---------------------------------------------------------------------------------------------
* * * Expedited Review * * *
PLEASE READ: For Expedited Review, all aspects of the research must include activities that (1) present no
more than minimal risk to human subjects, and (2) involve one or more of the specific categories listed below.
Select the following applicable categories to determine if your research project qualifies under Expedited Review.
If none of the categories are applicable to your research project, a Full Committee Review will be required. For
Expedited or Full Review, proceed to complete the following application.If none of the expedited criteria are
appropriate for your project, please move to the next screen WITHOUT checking any of these criteria; your
protocol will be reviewed by the full IRB. Note: The IRB will make the final determination if your protocol is eligible
for expedited review.
Select one or more of the following paragraph(s):
1.
Clinical studies of drugs and medical devices only when condition (a) and (b) are met.
a)
Research on drugs for which an investigational new drug application (21 CFR
Part 312) is not required. (Note: Research on marketed drugs that significantly
increases the risks or decreases the acceptability of the risks associated with
the use of the product is not eligible for expedited review.)
b)
Research on medical devices for which
i)
An investigational device exemption application (21 CFR Part 812) is not
required; or
ii)
The medical device is cleared/approved for marketing and the medical
device is being used in accordance with its cleared/approved labeling.
2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
a)
From healthy, non-pregnant adults who weigh at least 110 pounds. For these
subjects, the amounts drawn may not exceed 550 ml in an 8-week period and
collection may not occur more frequently than 2 times per week; or
b)
From other adults and children, considering the age, weight, and health of the
subjects, the collection procedure, the amount of blood to be collected, and the
frequency with which it will be collected. For these subjects, the amount drawn
may not exceed the lesser of 50 ml or 3 ml per kg in an 8-week period and

Page 11 of 47
 
collection may not occur more frequently than 2 times per week.
3.
Prospective collection of biological specimens for research purposes by non-invasive means.
Examples:
a)
Hair and nail clippings in a non-disfiguring manner;
b)
Deciduous teeth at time of exfoliation or if routine patient care indicates a need
for extraction;
c)
Permanent teeth if routine patient care indicates a need for extraction;
d)
Excreta and external secretions (including sweat);
e)
Uncannulated saliva collected either in an unstimulated fashion or stimulated by
chewing gumbase or wax or by applying a dilute citric solution to the tongue;
f)
Placenta removed at delivery;
g)
Amniotic fluid obtained at the time of rupture of the membrane prior to or during
labor;
h)
Supra- and subgingival dental plaque and calculus, provided the collection
procedure is not more invasive than routine prophylactic scaling of the teeth and
the process is accomplished in accordance with accepted prophylactic
techniques;
i)
Mucosal and skin cells collected by buccal scraping or swab, skin swab, or
mouth washings;
j)
Sputum collected after saline mist nebulization.
4.
Collection of data through non-invasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are not generally eligible for expedited
review, including studies of cleared medical devices for new indications.)
Examples:
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Physical sensors that are applied either to the surface of the body or at a
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be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some
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Research on individual or group characteristics or behavior (including, but not limited to, research on
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social behavior) or research employing survey, interview, oral history, focus group, program evaluation,

Page 12 of 47
 
human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category
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X 8.
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investigational device exemption where categories two through eight do not apply but the IRB has
previously determined that the research involves no greater than minimal risk and no additional risks
have been identified.
---------------------------------------------------------------------------------------------
* * * Background , Purpose , Study Procedures * * *
Study Title
Assessing the Malleability of Spatial Abilities in Individuals with Down Syndrome
Complete Sections 1 - 15. Specify N/A as appropriate. Do not leave any required sections blank.
1)
Background
a)
Describe past experimental and/or clinical findings leading to the formulation of the study, if
applicable.
Spatial ability is one of three categories of basic abilities, along with verbal and
quantitative abilities, that are the basis for developing many important independent
living skills (Park, Lubinski, & Benbow, 2000). Verbal and quantitative abilities are
prominently featured in school curriculum and assessments, whereas spatial ability
has often been completely overlooked or received only limited attention. According
to the National Academy of Sciences (2006) ”skill in spatial thinking is presumed
throughout the K – 12 curriculum, but is formally and systematically taught
nowhere.”  Little appears to have changed in the past 13 years. Hence, there is
heavy reliance on input from general experience rather than directed training to
produce facility with spatial abilities and skills in TD children (Halpern, 2013;
Newcombe & Huttenlocher, 2003).  Several researchers have indicated that
neglecting the importance of spatial ability can have widespread consequences for
typically developing (TD) children and adolescents (Wai, Lubinski, & Benbow,
2009). However, the discussion of the importance of spatial ability for TD children
tends to be focused on promoting interest and competence in STEM careers (Wai
et al., 2009). We argue here that spatial ability plays a more basic role in the
everyday functioning of persons with DS.  Indeed, spatial abilities have direct
applications to daily life, ranging from activities such as tying shoes to using hand
tools and navigating the environment. They also serve as a cognitive foundation for
many other complex skills such as solving mathematical problems and using
spatial language. Moreover, they are used in many specialty jobs such as grocery
stocking, packaging, and assembling, which are among the most commonly
reported jobs for adults with DS. We believe that the study of spatial abilities in
people with DS is necessary to minimize potential negative effects on basic daily
functions, independent living skills, and job possibilities. In previous research we
have reported difficulties in skills such as wayfinding that are particularly severe for
persons with DS. We have also observed difficulties in utilizing the specific spatial
abilities of mental rotation and perspective taking. The research proposed in this
application stems from observations that spatial abilities are relatively easy to
modify by increased experience with tasks that use spatial abilities in TD children

Page 13 of 47
 
and young adults (Uttal et al, 2013). Therefore, providing additional and intentional
opportunities to experience spatial tasks may be an important step in developing
methods for improving performance in spatial skills in persons with DS.
b)
Describe any animal experimentation and findings leading to the formulation of the study, if there is
no supporting human data.
N/A
2)
Purpose of the study
a)
Provide a brief lay summary of the project in <200 words. The lay summary should be readily
understandable to the general public.
Based on available literature and our own preliminary research, we have concluded
that persons with Down syndrome (DS) exhibit difficulties in utilizing the specific
spatial abilities of mental rotation and perspective taking, and performing complex
spatial tasks such as wayfinding and environmental learning. A weakness in spatial
abilities may have many direct applications to daily life, ranging from activities such
as tying shoes to using hand tools and navigating the environment. They also serve
as a cognitive foundation for many other complex skills such as solving
mathematical problems and using spatial language for giving and receiving
directions. Moreover, they are used in a variety of specialty jobs such as grocery
stocking, packaging, and assembling, which are among the most commonly
reported jobs for adults with DS. Hence, a new focus on spatial ability and its
modifiability in persons with DS is clearly warranted. The primary goal of the
research proposed in this application is to evaluate the malleability of mental
rotation and perspective taking in people with DS through providing intentional
experience with numerous spatial activities. Two groups of participants will be
tested over the course of the project: adolescents and young adults with DS and
typically developing children. Following an initial evaluation of performance on the
two abilities, participants will receive up to eight sessions of spatial activity
experience utilizing puzzle construction, block building, and computer search tasks.
Following the experience sessions they will be re-evaluated. These data will be
used to investigate two specific aims. First, we investigate whether spatial abilities
of persons with DS can be modified by experience with spatial activities. Second,
we investigate whether the degree of modification observed for persons with DS
can reduce performance differences between them and TD children. We also
consider whether performance on the PPVT, KBIT matrices, and Chronological
Age are associated with any benefits from spatial ability experience. To the best of
our knowledge, this is the first study to use experience with spatial activities to
improve spatial ability functioning in persons with DS, or persons with
intellectual/developmental disabilities in general for that matter.
b)
List your research objectives (specific aims & hypotheses of the study).
Specific Aim 1: The first specific aim is to demonstrate that spatial abilities are
malleable in persons with DS. Uttal et al. (2013) conducted a meta-analysis on
more than 200 spatial intervention studies in individuals of all ages demonstrating
that abilities are highly malleable and that even limited experience in spatial tasks
can produce positive and lasting effects in TD children and adults. Indeed,
numerous studies have shown that spatial ability performance of TD children and
adults can be achieved by providing experience with tasks that utilize spatial
abilities and do not require direct instruction (e.g., block play and puzzle
construction). It is reasonable to expect that these results will generalize to persons
with DS. However, this needs to be empirically evaluated. Hence, one important
goal of the proposed research is to demonstrate that experience with spatial tasks
can promote improvement in two specific spatial abilities (mental rotation and
perspective taking) in persons with DS. To test this specific aim, we will compare
spatial ability performance of persons with DS before and after varying levels of
experience with spatial activities.

Page 14 of 47
 
Specific Aim 2:  The second specific aim is to evaluate whether persons with DS
and TD children matched on nonverbal ability exhibit the same degree of
improvement as a function of similar experience with spatial abilities. If persons
with DS exhibit greater improvement than TD children, then it may be that the
weaknesses observed in spatial abilities reflect a lack of opportunity to engage in
spatial ability experience. If, on the other hand, persons with DS exhibit less
improvement, it may be that weaknesses observed in spatial abilities reflect a
lesser ability to benefit from intentional experiences. In the proposed research, we
will also evaluate the relations between degree of improvement and measures of
Nonverbal ability, Receptive Language, and Chronological Age to identify
differences in how these variables contribute to performance improvements in the
two groups. The results of these analyses may also help to identify persons with
DS who are most likely to benefit from spatial ability experience to promote
improvements in spatial abilities.
c)
Describe the study design (e.g., single/double blind, parallel, crossover, control, experimental,
observational, etc.)
N/A
Single blind
Double blind
Parallel
Crossover
X Control group
X Experimental group
Observational
X Other
Mixed Design (Between/Within Subjects) Pre-test/Post-test Comparison
d)
Provide a timeline for individual participant recruitment and follow-up (analysis for the study is
required).
Participants will be recruited from various sources including the UA Participant
Registry, DS Connect (NIH Registry of individuals with Down syndrome interested
in research), local schools, and local service providers. Following initial contact by
these various sources, participant families will self-identify to receive additional
information about the study - including a copy of the Parental Consent. The study
will take place over the course of 4 months for each participant, All participants will
receive the PPVT, the KBIT 2 Matrices subtest, an assessment of Mental Rotation,
and an assessment of Visual Perspective Taking during the first testing session
(Approximately 45 minutes). Mental Rotation and Perspective Taking performance
will be assessed two additional times for all participants, once following Experience
Session 16 and once following Experience Session 32. These two assessments
will take approximately 15 minutes. Experience sessions will be provided twice per
week, with each session lasting approximately 30 minutes over a period of 16
weeks. Half of each group (No Delay participants) will begin spatial ability
experience during a first experience session scheduled approximately one week
following the initial assessment. The other half of each group (Delay participants)
will not begin the spatial ability experience for the 8 weeks following the first
assessment and serve as a control for practice effects on the assessment
measures. The Delay participants will receive a second assessment on the Spatial
Abilities and begin spatial ability experience during week 9. They will receive the
same protocol as the experimental participants following the second assessment (8
weeks experience, ability assessment, 8 weeks experience, ability assessment).
The final assessment will come following Experience Session 32 (week 16). Data
analysis is planned upon the completion of all data collection during year 03 of the

Page 15 of 47
 
project period.
e)
Will participant be randomized?
Y
f)
If participants will be given placebo, please justify placebo use, and describe contents of the
placebo.
NA
3)
Study Procedures
a)
Is this project a multicenter study (i.e., same project is conducted elsewhere by a different
investigator)?
Y
Is University of Alabama acting as a coordinating center for other sites?
Y
Will the University of Alabama site be participating in all parts/procedures/arms of the study?
Y
If No, explain what University of Alabama will NOT participate in:
b)
Describe all the procedures, from screening through end-of-study, that the human participant must
undergo in the research project, including study visits, drug treatments, randomization and the
procedures that are part of standard of care. Specify which procedures are for research and which
are standard of care. If study involves only retrospective record review, describe that review process
here, including how records will be selected for review. Please note: The box below is for text only. If
you would like to add tables, charts, etc., Click "Add" to attach the documents.
The initial assessment will include four measures:
Ravens 2 Matrices: The Ravens 2 Matrices is a 60 item measure of nonverbal
ability. The subtest measures a participant’s ability to solve problems, identify
relationships, and complete visual analogies without testing language skill. The
examiner shows the participant pictures or abstract designs that follow a pattern,
with one element missing. The participant is instructed to point to a picture that will
complete the pattern. Participants will be matched on raw score performance.
Completing the subtest should take less than 15 minutes for most participants.
PPVT-4: The PPVT – 4 is a norm-referenced test for measuring receptive
vocabulary of children and adults. The test is administered individually. Each item
consists of four colored pictures that serve as response choices on each page. For
each item, the examiner says a word and the examinee selects the picture option
that best represents the word’s meaning. The test is normed for 2 years, 6 months
to 90 years. Average time to administer the test is 10 – 15 minutes.
Mental Rotation Assessment - On each trial, participants will be presented a
geometric shape (e.g., a block letter L) in the center of a computer screen that
completes one of two rectangles presented at the bottom of the same screen. The
open area in one rectangle is the mirror image of the open area in the second
rectangle. The shape in the center of the screen will fit one of the rectangles when
horizontal. The shape can be rotated from horizontal by 0, 45, 90, 135, 180, 225,
270, or 315 degrees. Participants respond by touching the rectangle into which the
shape will fit once oriented properly (using touchscreen technology). Participants
receive 4 trials at each orientation.
Perspective Taking - Participants will be seated at a table with four chairs and four
different objects (street lamp, mailbox, stop sign, traffic signal) representing each
location on the corner of a city block in front of each chair. A stuffed animal is
placed behind each object. One experimenter walks around the table stopping at
each location. At each location, the participant is told that the experimenter is
taking a picture from that location and he/she is asked to look at four pictures. The
task is to select the picture that the experimenter has just taken. The four pictures
consist of the participant’s point of view, a mirror image of the participant’s point of
view, the experimenter’s point of view, and a mirror image of the experimenter’s
Due to CoVid
Restrictions,
Procedures were
adapted for online
presentation via 
Zoom. Ravens and
PPVT-4 used available
commercial formats.
Mental Rotation and
Perspective Taking 
involved the creation of
Video presentations. 
Online presention was
approved by the 
University IRB on 
03/04/2020.

Page 16 of 47
 
point of view. This task will take 5 - 10 minutes.
Assessments 2 and 3 will include only Mental Rotation and Perspective Taking
Assessments.
Spatial Ability Experience will include two tasks of Object manipulation and two
Large Environment Experiences. These tasks are meant to provide experience.
Object Manipulation Experience: Two categories of tasks will be used to provide
object manipulation experience: LEGO Block Play and Puzzle Construction. One
task will be used in each spatial ability experience, with tasks alternating between
sessions.
LEGO Block Play: Participants and experimenter will each have 20 multi-colored
and multi-shaped connecting blocks. During play, the participant and experimenter
will alternate creating structures and copying what the other has created during the
15 minute interval. No specific corrective feedback will be given during the
experience, although participants will be asked if they think their construction
matches the model. Object manipulation rather than accuracy is the basis of the
experience. Participants will be allowed to take as long as they need to complete
their copy of each structure.
Puzzle Construction: We will select puzzles that include 4, 8, 12, 16, or 20 puzzle
pieces. All puzzles will have pieces that need to be rotated to fit the puzzle board to
provide the necessary object manipulation experience. The puzzle board will also
include the outline of the shapes of the pieces. Hence, participants will need to
match the outline of the piece with the rotated actual piece to efficiently complete
the puzzle. Touching each piece with a finger will rotate the piece, and removing
the finger will stop the rotation. Participants will be given five puzzles to complete
during the experience session. They will be given 3 minutes to complete each
puzzle. If they complete the puzzle, they will receive the next larger size puzzle for
their next opportunity. If they fail to complete the puzzle, the size of the puzzle will
be reduced by one level.
Large Environment Experience: Two categories of tasks using a large scale virtual
environment will be used to provide object manipulation experience: Hide and Seek
and Wayfinding. One task will be used in each spatial ability experience, with tasks
alternating between sessions.
Hide and Seek Video Game: The setting will consist of a classroom with four
different color doorways. The participant will be identified as an avatar (self-
selected) in the center of the classroom. A second avatar will represent a person
hiding behind one of the doors. The doors will be described as “see through” from
the perspective of the hiding avatar. The participant will be shown a panoramic
view of the classroom. Then he or she will be shown the view from the hiding
avatar. The view will return as the point of view of the participant avatar and the
participant will be instructed to find the door that the second avatar is hiding behind.
The participant will be allowed to look behind any door to find the hiding avatar. If
the participant selects the wrong door, they will be shown the view of the hiding
avatar again and asked to continue the search. Once found, the avatar will be
placed behind a second door and the procedure will be repeated. There will be four
trails per session.The experimenter will record the number of wrong locations that
were searched and the time to find the hiding avatar for each search event. Time
for this task will be approximately 15 minutes.

Page 17 of 47
 
Wayfinding Video Game: We will introduce the participant to an environment (e.g.,
a shopping mall) and allow them to explore the environment looking at the different
stores and items in the stores for 5 minutes. We will then ask them to shop for
particular items in the various stores. For each item, they will need to start from a
different location in the mall (i.e., the shop in which they made their last purchase).
Hence, to make a correct initial choice of a turn when leaving the store, participants
will need to be able to reconstruct their environment from a different perspective.
We will ask them to locate up to 5 items for a maximum of 10 additional minutes.
The experimenter will record whether or not the participant made a correct initial
turn choice leaving the starting point, how long it took to get the correct item
location, and how many items they had time to locate during the session. Total time
will be 15 minutes.
We are seeking permission from participants to record the ZOOM feed of
participant performance on the Spatial Ability and Verbal Ability tasks.
c)
Provide stopping rules for the study, If the proposed study is a clinical trial where a drug, vaccine,
device or other treatment is compared to a placebo group or comparison treatment group, what are
the guidelines or endpoints by which early decisions regarding efficacy or lack of efficacy can be
made? For example, it may be reasonable to stop enrollment on a study when efficacy has already
been clearly demonstrated, to avoid unnecessary enrollments of additional participants.
Alternatively, it may be reasonable to stop enrollment when it is clear that efficacy will never be
demonstrated, given the statistical power of the study as designed. Describe the guidelines that are
in place to assist in making these determinations, if relevant to the proposed study.
NA
d)
Describe how data analysis will be performed (statistical tests, methods of evaluating data) and
indicate the smallest group/unit for which separate reporting will occur. For studies involving a
questionnaire, if data and reliability information are available, please describe or provide references.
(Page numbers from a sponsor's protocol/grant may be referenced in this section).
The independent variables of interest will be Group (DS and TD), Delay (No Delay
and Delay), and Assessment (1, 2, and 3). The smallest number of participants in
any given cell of the design is 20 participants.
Specific Aim 1 evaluates the malleability of MR and PT performance in participants
with DS. Consistent with Aim 1, we will apply Multivariate ANOVA to the subsample
of DS children. If the test for sphericity is significant, we will interpret the
multivariate tests for the within subject effects. If not, we will use the univariate
tests due to their increased statistical power. With either option, the test for the
effect of Assessment, if significant, would indicate that performance of the DS
children improves over time.  We will then evaluate the interaction of
AssessmentDelay, which if significant would signify that Delay vs No Delay
participants exhibit a different magnitude of improvement across Assessment
times. One contrast of interest compares Delay vs No Delay participants at
Assessment 2. Performance favoring the No Delay participants would indicate a
significant effect of spatial ability experience. A second contrast of interest
compares Assessment 3 performance to Assessments 1 and 2 for the Delay
participants. If we are able to confirm that the Delay participants exhibit higher
scores at Assessment 3 than at Assessments 1 and 2 (which should not differ) then
the benefits of spatial ability experience for persons with DS would be further
confirmed.
Specific Aim 2 evaluates possible differences in rate and magnitude of
improvement of DS and TD participants. We will approach Aim 2 in a very similar
statistical manner. For Aim 2a, we will apply Multivariate ANOVA to the whole
sample to test for the effect of AssessmentGroup. If significant, it is indicative that
DS and TD participants do not exhibit the same degree of improvement following
training. If improvement in performance is greater for the participants with DS, it

Page 18 of 47
 
would indicate that experience may be a primary contributor to initial differences in
spatial abilities of the DS and TD participants. If improvements are greater for TD
children or similar for both groups, it would suggest that initial differences in spatial
abilities between groups are not solely due to differences in experience. We will
also examine the interaction of Assessment Group Delay complemented with
contrasts to explore more closely how participants with DS compare to TD children.
For example, we will compare rate of change over Assessments to see if the
participants with DS need more experience to reach the same level of performance
as the TD children. This may indicate the need for more intensive training for
participants with DS to modify spatial ability performance.
---------------------------------------------------------------------------------------------
* * * Radioisotopes or Radiation Machines * * *
4)
Radioisotopes or Radiation Machines
Please note: For projects requiring radiation procedures, please contact the UA Environmental
Health and Safety Office at 348-6010
a)
If applicable, summarize in lay language the radiographic diagnostic and therapeutic procedures associated
with this protocol. (X-ray, fluoroscopy, CT, radioactive materials, nuclear medicine, PET-CT, radiation
oncology, accelerator, Cyber Knife procedures, etc.).
b)
Are the radiation procedures being performed a normal part of the clinical management for the medical
condition that is under study (Standard of Care), or are the procedures being performed because the
research participant is participating in this project (extra CT scans, more fluoroscopy time, additional
Nuclear Medicine Studies, etc.) (Not Standard of Care)? If some procedures are Standard of Care and
some are Not Standard of Care, check both boxes.
NOT STANDARD OF CARE
STANDARD OF CARE
If it is not standard of
care,complete the rest of
this section. Provide the
University of Alabama
RSC approval
information below.
If it is only standard of
care, skip the rest of this
section.
c)
Are research-related radiation procedures limited to X-rays only?
Yes (Complete X-ray table).
No (Skip X-ray table).
d)
Total Radiation Exposure (in mRems) from x-ray procedures:
To calculate radiation exposure from x-rays only, University of Alabama allows use of the
Duke University Radiation Safety Committee dose estimate calculator. University of
Alabama does not allow use of this website to calculate any other type of radiation
exposure.
To determine the dose estimate, click on the appropriate links, below (you will be taken to
the Duke University Radiation Safety Committee website). Enter the x-ray procedures
into the appropriate fields of the website and click "create statement". Enter the dose
estimate from the statement in the table above.
For studies involving adults, please click here.
For pediatric studies, please click here..
e)
Please list all radiation procedures (including x-ray) that are research-related (not standard of care). Include
the anatomical location and specify the number of times that each procedure will be conducted throughout
the entire study.
NOTE: The IRB will determine if this study requires radiation safety review by the Radiation
Safety Officer or the Radiation Safety Committee.

Page 19 of 47
 
For more information on how to submit for radiation safety review, contact the Radiation
Safety Officer.
---------------------------------------------------------------------------------------------
* * * Drugs, Reagents, Chemicals, or Biologic Products * * *
5.
Drugs, Reagents, Chemicals, or Biologic Products
Pilot
Phase I
Phase II
Phase III
Phase IV
Not Phased
a)
Please list in the space below all investigational drugs, reagents or chemicals to be
administered to participants during this study.
b)
Please list in the space below all FDA approved drugs, reagents, chemicals to be
administered to participants during this study.
Please read the IND Statement 1 and  IND Statement 2.
---------------------------------------------------------------------------------------------
* * * Devices * * *
6.
Devices
a)
Please list in the space below all investigational devices to be used on participants during this study.
b)
Please list in the space below all FDA approved devices to be used on participants during this study.
---------------------------------------------------------------------------------------------
* * * Subject Population(a-h) * * *
7.
Subject Population - In the space below, please detail the participants that you are requesting to recruit
(include description of each group requested)
a)
Expected age range of participants. (For example - 19 yrs to 90 yrs).
Participants with Down syndrome will be between 10 and 30 years of age.
Typically developing children will be between 4 and 9 years of age.
We will test 48 participants per group - plus an additional 6 typically developing children
as needed to provide a closer match on nonverbal ability for the children in the
Experimental condition with the children in the control condition.
b)
i) Number to be directly solicited for this research.
X N/A
ii) Number to be consented (including withdrawals or screen
failures)
N/A
102
iii)Number expected to complete the study.
102
c)
If this is multi-center study, number of participants to complete
the study study-wide
N/A
102
d)
If study involves review of medical or other records, number of
records to be reviewed.
X N/A
e)
If women, minorities, or minors are excluded, a clear compelling rationale must be provided unless not
applicable. Examples for not including minors: disease does not occur in children; drug or device would
interfere with normal growth and development; etc.
NA
f)
Describe how potential participants will be identified for recruitment (e.g., chart review, referral from
individual's treating physician, those individuals answering an ad). How will potential participants learn
about the research, and how will they be recruited (e.g., flyer, e-mail, web posting, telephone, etc.)? State
where recruitment materials will be located. Click "Add" to upload recruitment materials document.

Page 20 of 47
 
Important to remember: Study Activities cannot begin until IRB approval is granted.
General Information: Potential recruitment sites are identified and we provide them with
information about the study. We ask them to identify potential participants and to send
recruitment and consent information to the parents/guardians of the identified
individuals. We do not get any identifying information on individuals at this point in time.
Participants self-identify to the researchers by returning signed consent forms with
contact information or by requesting additional information about the study. We will not
contact any individuals who have not identified themselves as interested in the study.
Information to be discussed with recruitment sites and a draft letter for them to send to
parents/guardians is attached.
The University of Alabama participants with DS will be recruited from the University of
Alabama Intellectual Disabilities Participant Registry that was established with NICHD
Recovery Act Funding (Conners, PI). Participants will also be recruited through local DS
organizations like DS Alabama, DS Connect, and through local public schools. Montclair
State University participants with DS will be recruited from local service providers, DS
Connect, and local public schools. The lead PI at Montclair State has established
research relationships with these organization in the past several years. Twenty-four
participants will be tested at UA and 24 at Montclair State University.
Typically developing children will be recruited from local preschools and elementary
schools, including The University of Alabama Children’s Program and the Montclair
State University preschool program. Twenty-seven participants will be recruited from
each site.
We have secured permission from the CDRC (see attached permission email) and
recruited typically developing children from that site. We are adding the following
organizations for recruitment and will be contacting them about recruitment following
approval of the new recruitment materials. We will be identifying additional recruitment
sites in the future that will be added to the list once contact is made.
https://childrenhelpingscience.com/
Massachusetts Down Syndrome Congress
Global Down Syndrome Organization
New Jersey Down Syndrome Organization
The new recruitment materials include Flyers and access to the PIs research web page.
These are attached to the current protocol for review. Ed Merrill's research web page is
visible for a short time if you would like to view it formatted. Organizations have not
been invited to view the page prior to approval. The Web Page address is:
https://emerrill.people.ua.edu/research.html
 Letters of support from organizations assisting with recruiting efforts will be provided to
the IRB. WE have attached an email approving recruitment from The University of
Alabama CDRC.
---------------------------------------------------------------------------------------------
* * * Subject Population(i-l) * * *
7.
Subject Population (continued)
i)
Inclusion and Exclusion Criteria.
Identify inclusion criteria.
All participants must meet the following enrollment criteria based on parental report: (1)
adequate vision for tasks in this study, (2) adequate verbal skills for understanding
instructions for tasks, and (3) no accompanying diagnoses of Autism Spectrum Disorder
as autism symptomology could confound results.

Page 21 of 47
 
Identify exclusion criteria.
No additional exclusion criteria are established.
j)
Compensation. Explain the amount and schedule of compensation, if any, that will be paid for participation
in the study. Include provisions for prorating payment.
Participants will receive a Tablet computer (Valued at Approximately $75) and $100 for
completing the study. If a participant cannot complete the study, they will receive
payment at the rate of $25 dollars for starting each of the four months of the study.
If approved, we will be offering parents and parents to complete the project in less time
by increasing the number of experience activities completed each week. If parents
choose this option, they will be paid $25 for completing each 25% of the scheduled
activities (4 experiences with each of the 4 activities).
k)
Describe who will cover study related costs. Explain any costs that will be charged to the participant.Include
provisions for prorating payment.
There are no costs to participants.
l)
Estimate the probable duration of the entire study including data analysis and publication. This estimate
should include the total time each participant is to be involved and the duration the data about the
participant is to be collected. If the study is Investigator-initiated, a timeline for individual participant
recruitment, follow-up, total time for participant accrual, and data analysis for the study is required.
Each participant will be enrolled for approximately 17 weeks following completion of the
consent process. This translates into two sessions per week, with two experience
activities per session. We now believe the activities will take approximately 10 minutes
per session. (Participants will be recruited on a rolling schedule, with different
participants recruited and tested throughout the duration of the study. Data collection for
the study is projected to take approximately 3 years. Data analysis and publication
should take place in the year following data collection - for a total time of 4 years.
Initial participants have inquired about the flexibility of this schedule. From a research
integrity perspective, we believe it is feasible to conduct the study in less time per person
if they are willing and able to complete additional experience activities during each week.
We would like to provide participants with the option of completing up to twice as many
activities during each week - reducing time to complete the study by half. This can be
done by increasing the number of sessions per week or increasing the number of
activities per session. Care will be taken to ensure that participants do not become
fatigued during there sessions. We will complete no more than twice the activities in any
given session, and no more than twice the number of sessions per week.
---------------------------------------------------------------------------------------------
* * * Subject Population(m) * * *
Research Involving Children
NOTE: Investigators, please include this information with the e-Protocol application if your research involves
children. In Alabama a child is an individual less than 18 years of age unless the child is legally emancipated. If
your research involves children with more than one vulnerability (e.g., children who are pregnant, incarcerated, or
cognitively impaired) attach the supplementary information for that vulnerable population as well.
Minimal risk means that the probability and magnitude of the harm or discomfort anticipated in
the research are not greater in and of themselves than those ordinarily encountered in daily
life of a healthy child or during the performance of routine physical or psychological exams or
tests.
Section 1.
Select and complete the category that applies to your research.
X Category 1 (45 CFR 46.404; 21 CFR 50.51)
My research does not involve greater than minimal risk.

Page 22 of 47
 
a)
My research falls under this category because:
My research involves research on individual or group characteristics or behavior
(including perception, cognition, language, social behavior, etc.) or research employing
survey, interview, focus group, program evaluation, human factors evaluation, or quality
assurance methodologies. The probability and magnitude of the harm or discomfort
anticipated in the research are not greater in and of themselves than those ordinarily
encountered in daily life of a healthy child or during the performance of routine physical
or psychological exams or tests. No deception isinvolved.
b)
Describe what provisions will be made for soliciting the assent of the children, and the
permission of both parents, or the legal guardian.  (Permission from both parents must be
obtained unless one parent/guardian is deceased, unknown, incompetent, or not
reasonably available, or when only one parent/guardian has legal responsibility for the
care and custody of the child). Justify reason(s) if seeking permission from only one
parent.
Parents will be sent information about the study and signed consent is required prior to
asking children to participate. Children will be told about the study and will be included
only if they assent to volunteer for the study.
We only plan to obtain signed consent from one parent for the following reasons. First,
the study is minimal risk and only requires that participants engage in behaviors similar
to those of their daily lives. Second, we do not have the means to firmly establish family
status for families of participants to determine if both parents are available for consent.
Third, and most importantly, the failure include participants of families without two
parents available to consent will render the sample ungeneralizable to the population as
a whole and have the likely and inadvertent effect of disproportionately eliminating
potential participants from minority and lower SES groups.
Category 2 (45 CFR 46.405; 21 CFR 50.52)
My research involves greater than minimal risk but presents the prospect of direct benefit to
the individual participants.
a)
My research falls under this category because:
b)
Justify the risk(s) by explaining the anticipated benefit to the participants:
c)
Explain how the relation of the anticipated benefit to the risk is at least as favorable to the
participants as that presented by available alternative approaches:
d)
Describe what provisions will be made for soliciting the assent of the children, and the
permission of at least one parent/guardian.  (Permission from both parents must be
obtained unless one parent/guardian is deceased, unknown, incompetent, or not
reasonably available, or when only one parent/guardian has legal responsibility for the
care and custody of the child). Justify reason(s) if seeking permission from only one
parent.
Category 3 (45 CFR 46.406; 21 CFR 50.53)
My research involves greater than minimal risk, and no prospect of direct benefit to
individual participant, but likely to yield generalizable knowledge about the participant's
disorder or condition.
a)
My research falls under this category because:

Page 23 of 47
 
b)
Describe how the risks for participating in your research represent a minor increase over
minimal risk (i.e., the children being recruited have a disorder or condition that would
place them in a group other than an average healthy child; therefore, the research
qualifies as a minor increment over minimal risk.  This risk is slightly more than what the
average healthy child would experience, but is reasonable for these participants because
it is not more than they would experience or expect given their condition.).
c)
Describe how the research intervention(s)/procedure(s) present experiences to
participants that are reasonably commensurate to those inherent in their actual or
expected medical, dental, psychological, social, or educational situations:
d)
Explain why the intervention or procedure is likely to yield generalizable knowledge about
the participants' disorder or condition, which is of vital importance for the understanding
or amelioration of the participants' disorder or condition:
e)
Describe what provisions will be made for soliciting the assent of the children, and the
permission of both parents/guardians.  (Permission from both parents must be obtained
unless one parent/guardian is deceased, unknown, incompetent, or not reasonably
available, or when only one parent/guardian has legal responsibility for the care and
custody of the child). Justify reason(s) for seeking permission from only one parent.
Category 4 (45 CFR 46.407; 21 CFR 50.54)
My research does not fall under Category 1, 2, or 3 listed above.  However, the research
presents a reasonable opportunity to understand, prevent, or alleviate a serious problem
affecting the health or welfare of children.
(NOTE:  If your research is funded by, or funding has been sought from the Department
of Health and Human Services (DHHS), Department of Education, or is FDA regulated, a
report must be sent for review to the DHHS Secretary, Secretary of the US Department
of Education, or Commissioner of FDA. If this category is applicable, the Office of
Research Compliance will prepare and submit a report of IRB review to the appropriate
federal official(s)).
a)
My research falls under this category because:
b)
Describe what provisions will be made for soliciting the assent of the children, and the
permission of both parents/guardians. (Permission from both parents must be obtained
unless one parent/guardian is deceased, unknown, incompetent, or not reasonably
available, or when only one parent/guardian has legal responsibility for the care and
custody of the child). Justify reason(s) if seeking permission from only one parent.
Section 2.
In order to effectively assess and evaluate the risk of your proposed research to children, the
IRB requires the following information.  Respond to all items.
a)
Provide justification for the participation of children as research participants in your study.
The children used in this study are necessary for providing a comparison group matched
on non-verbal ability with participants with Down syndrome. In this type of research, it is
necessary to evaluate the performance of individuals with Down syndrome against
participants who are matched on general ability measures to determine if the difficulties
associated with Down syndrome are beyond that which would be expected based on
developmental level.

Page 24 of 47
 
b)
Has this research been conducted in adults?
Y
If yes, is there any indication that the proposed research would benefit, or at least not be
harmful to children?
Similar research has been conducted in adults and children with no adverse effects.
The children are essential for providing a comparison group for the participants with
Down syndrome.
c)
Indicate how many children you propose to enroll in the study and justify this number
(whenever possible, involve the fewest number of children necessary to obtain
statistically significant data which will contribute to a meaningful analysis relative to the
purpose of the study).
All of the typically developing participants will be children (48 participants originally
planned). Many of the participants with Down syndrome will also be participants (we
anticipate about half of the 48 participants in this group, or 24). The total number of
participants was determined by power analysis. A 4 groups x 3 repetitions analysis with
alpha set at .05, power set at .80, and total N = 96 (24 in each group) would be sufficient
observe a significant effect size (f(V)) of .27 or greater. To evaluate the power for simple
effects tests to compare the effects of training for the DS and TD participants separately,
we conducted a 2 groups (Delay and No Delay) x 3 repetitions analysis with alpha set at
.05, power set at .80, and total N = 48 (24 in each group). Power analysis indicated that
48 total participants would be sufficient to observe a significant effect for effect sizes (f(V)
of .27 or greater for main effects of Delay and of .25 or greater for main effects of
Assessment Time. Power calculations were conducted in GPower 3.1.9.2 (Faul et al.,
2007). However, we are requesting and additional 6 typically developing participants at
this time to make it possible to better match the Experimental and Control group children
on nonverbal ability.
d)
Describe how assent of a child will be obtained and documented (if applicable).  If not
applicable, explain why.
The different procedures will be described to the participant at the start of each session.
They will then be asked if they want to take part in the current days activities. We will
only continue if the participant agrees to continue. We will record whether or not assent
was given on our daily record sheet before continuing on each day.
I am requesting waiver of the requirement for assent.
Justify:
OR
I have attached an assent form/assent script for IRB review.
Y
e)
Explain what methods will be used for evaluating dissent (i.e., description of behaviors
that would indicate child does not want to participate (such as moving away, certain facial
expressions, head movements, etc...).
If children indicate they do not want to perform the activities or appear reluctant to
perform the activities by resisting, frowning, shaking their heads, etc.) we will discontinue
the activities for the day. If they appear reluctant to continue for multiple sessions (i.e.,
two in a row without explanation) they will be discontinued from the study.
f)
Describe how parental permission will be obtained. [Note: If you propose to waive the
requirement for parental permission (i.e., getting parental permission may be against the
best interest of the child, i.e., a study of abused or neglected children), describe what
measures will be taken to protect the rights and welfare of the children.]
The study consent will be sent to parents and they will be asked to return it via mail or in
person. They will be given the opportunity to call the PI to request additional information.
Participants will be asked to be in the study only after a signed consent has been

Page 25 of 47
 
returned to the experimenter.
I am requesting waiver of the requirement for parental permission.
Justify:
OR
I have attached a parental permission form for IRB review.
Y
g)
Describe measures that will be taken to ensure that a parent is present when the child
participates in any research interventions or procedures. [Note:  If the nature of the
research is such that it is not appropriate to have a parent present (i.e., research into
sensitive personal issues, physical examinations of teenagers, etc...) please explain why.]
Parents will be required to be in the home or on campus when their children are tested to
ensure their presence in case of an emergency. If the parent cannot be present, testing
will be rescheduled.
h)
Describe the expertise of the research staff/study personnel for dealing with children at
the ages included and whether they are knowledgeable and sensitive to the physical and
psychological needs of the children and their families.  Describe the appropriateness of
facility in which the research will be conducted in relation to environment and/or
equipment accommodating to children.
Drs. Merrill, Conners, and Yang have been conducting research with children for many
years and are knowledgeable and sensitive to the needs of child participants and
families. All Graduate and Undergraduate student Research Assistants will be trained by
these faculty. Before they will be allowed to conduct the project on their own, they will
participate in sessions with the faculty, and then observed by the faculty when they first
take the lead role in conducting the sessions. Two RAs will be present during all testing
sessions as an added measure to ensure that the needs of participants are met. We
anticipate that most sessions will take place in the participants home. When taking part
on campus, rest room facilities and a break area with approved snacks will be provided
as needed.
i)
If applicable, provide any additional information that may support your request to involve
children in this research.
---------------------------------------------------------------------------------------------
* * * Subject Population(n) * * *
Research with cognitively impaired persons
NOTE:  Investigators, please include this form with IRB application if your research involves cognitively impaired
(decisionally impaired or decisionally challenged) persons.  If your research involves people with more than one
vulnerability, please complete the supplementary form for that population as well.
The IRB may ask you to designate an impartial observer to monitor the consent process or it may send its own
representative to do so.
Section 1.
Note:Check the box next to the category that in your best judgment applies to your research,
and provide the information requested in the space provided.
Note: Minimal risk means that the probability and magnitude of the harm or discomfort
anticipated in the research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical or psychological exams
or tests.  (i.e., daily life of health persons)
X Category 1
My research does not involve greater than minimal risk.

Page 26 of 47
 
Explain.  If appropriate, describe what  provisions are in place for allowing a Legally
Authorized Representative (LAR) or other person with the participant's best interests at
heart to assist the participant in navigating the research process:
We will require parental/guardian consent even if the participants with Down syndrome
are adults. Adult participants with Down syndrome will also be required to sign a consent
form.
Category 2
My research presents greater than minimal risk and prospect of direct benefit to the participants.
Explain.  If appropriate, describe what provisions are in place for allowing a Legally
Authorized Representative (LAR) or other person with the participant's best interests at
heart to assist the participant in navigating the research process.
Category 3
My research presents greater than minimal risk and no prospect of direct benefit to the participants, but likely
to yield generalizable knowledge about the participant's disorder or condition, because:
Explain.  If appropriate, describe what provisions are in place for allowing a Legally
Authorized Representative (LAR) or other person with the participant's best interests at
heart to assist the participant in navigating the research process.
Category 4
My research does not fall under Category 1, 2, or 3, listed above.
If you check this category, the IRB determines additional safeguards on a case-by-case basis.
Section 2.
1.
Explain why individuals with impaired decision-making capacity are suitable for this
research. If the objective(s) of the study allow for inclusion of competent participants,
provide compelling justification for inclusion of incompetent participants.
The research has a primary goal of assessing malleability of spatial skills of persons with
Down syndrome. These abilities are known to be deficient in Down syndrome and are
particularly important in several aspects of daily functioning (e.g., navigation, work).
Hence, it is necessary to evaluate whether or not these abilities are modifiable in persons
with Down syndrome.
2.
Describe who will determine individuals' competency to consent and the criteria to be
used in determining competency (e.g., use of standardized measurements, consults with
another qualified professional, etc...).
Parents will provide the necessary consent for participation.
3.
It should be recognized that decision-making capacity may fluctuate, requiring ongoing
assessment during the course of the research. Is it reasonable to expect that during
the course of the research, subjects may lose their capacity to consent or their ability
to withdraw?
N
a)
Describe what provisions are in place for periodic re-consent. Include the rationale
and procedure,  the proposed interval,  any changes in behavior that might signal
the need to re-consent whether or not the proposed interval has elapsed, and any
consultative resources that are available for these decisions.  Describe the process
for re-consent or re-assent, or reassessment of willingness to continue participation.
b)
Describe what provisions are in place to protect the participants' rights in the event
they lose their capacity to consent or their capacity to withdraw during the course of
the research. (e.g., power of attorney, consent a caregiver as well as the patient,
etc.).

Page 27 of 47
 
c)
Describe what provisions are in place for use of additional waiting periods to allow
potential participants time to consult with family members about whether or not to
participate.
4.
Explain how you will identify who is authorized to give legally valid consent on behalf of
any individual(s) determined to be incapable of consenting on their own behalf.
Our approach to consent to participate will include two steps. First, initial contact of
potential participants with Down syndrome will always be made through
parents/guardians or organizations/service providers who work with the individuals with
Down syndrome. Persons with Down syndrome will never self identify for the study.
Organizations/Service providers will identify persons eligible to provide valid consent for
potential participants in their system. Parents/Guardians will be presumed to have that
authority if they respond on behalf of their child. Once identified, we will get signed
consent from parents/guardians to ask their children to volunteer to participate in the
project. Participants below the age of majority to consent for research and those who are
deemed ineligible to consent for themselves due to cognitive impairment will be covered
by the signature of parents/guardians. Second, all participants will only be included if
they agree through assent or consent to participate. Participants below the age of 18 (the
youngest age of majority we have found) will be required to provide verbal assent.
Participants above the age of 18 will provide signed Assent/Consent using the document
provided. Participants above the age of majority to consent to participate in research and
participants deemed eligible to sign for themselves by the parents/guardian will be
covered by their own consent document. For the rest, the signature will be treated as
assent to participate, with the consent of the participants’ parents/guardians providing the
necessary informed consent documentation. All rights and considerations due to
participants will be bestowed on the basis of these two signed documents. We will use
the consent forms that have been approved by the IRB already. At this time, we have
identified the age of majority to participate in Clinical Trials research to be 18 years for
most states, with exceptions being Indiana (21), Mississippi (21), Nebraska (19), and
New York (21).
5.
Explain the criteria you will use for determining when assent is required for participants
who are not competent.
The study procedures will be described in terms that are understandable. All individuals
will be informed that it is their choice to participate. They will be given the option to say
they do not want to participate. They will only be included if they respond to our request
to participate in the affirmative.
6.
Explain what methods will be used for evaluating dissent (e.g., description of behaviors
that would indicate individual does not want to participate (such as moving away, certain
facial expressions, head movements, etc...).
Participants who are slow to engage in the procedures, frown or shake their heads while
participating, or appear reluctant to continue will be excused for the current session. IF
they appear reluctant for two sessions in a row - they will be excused from the study.
7.
The research protocol should include someone who can be reasonably assumed to have
the participant's best interest in mind and can assist the participant in navigating the
consent and research process. A person holding durable power of attorney or other legal
designee, spouse, close relative who is involved in ongoing care of participant, other
person with a personal or blood relationship who is involved in ongoing care of
participant, or other close relatives or friends may assume this role.  Describe how
individuals will be identified to serve in this capacity.  If this request is not appropriate for
this study, justify why it should be waived.

Page 28 of 47
 
Parents/legal guardians will serve this purpose.
8.
If applicable, describe when and how the individual's health care provider will be
consulted prior to participation in the research.  NOTE:  If the Principal Investigator (PI) is
also the individual's health care provider, address how the PI will separate the roles of
clinician and researcher.
NA
9.
Will the research interfere with current therapy or medications?
N
If yes, describe what the changes may entail (i.e., if the subjparticipantl be removed from
routine drugs/treatments, wash out periods, etc.) and the potential risks.
10. Does your research involve institutionalized individuals?
N
a)
Justify the use of institutionalized individuals and explain why non-institutionalized
individuals can not be substituted.
Section 3.
Complete this section if your research involves individuals from the Department of Veterans
Affairs (VA).
1.
Address procedures you will use to ensure the participant's representative is informed
regarding his/her role and obligation to protect the incompetent participant or person with
impaired decision-making capacity.
N/A
2.
Address procedures you will use to ensure the participant's representative has been told
of his/her obligation to try to determine what the prospective participant would do if
competent, or if the prospective participant's wishes cannot be determined, what the
participant's representative thinks is in the incompetent person's best interests:
N/A
3.
The VA has specific requirements and procedures for determining and documenting in
the person's medical record that an individual is incompetent or decisionally-impaired.
There are additional requirements if the lack of decision-making capacity is based on
diagnoses of mental illness.  These requirements are outlined in the Veterans Health
Administration (VHA) Handbook 1200.5, Section II.   Have you reviewed these
requirements and included them in your procedures?
N
4.
Justify that the research involves no significant risks, or if the research presents
probability of harm, justify that there is at least a greater probability of direct benefit to the
participant:
N/A
Note:[Veterans Health Administration Handbook 1200.5, July 15, 2003, Section 11 - Research
Involving Human participants with Surrogate Consent, and Appendix D Vulnerable
Populations, Section 6(c)]
Section 4.
For research involving cognitively impaired persons outside the state of Alabama, also
complete this section.
a)
Provide information regarding the state definition of legally authorized representative,
child, decisionally-impaired, or guardian, as applicable to the research and to the federal
definitions.  [If the research is to be conducted in more than one state outside of
Alabama, provide this information for each state.]

Page 29 of 47
 
Note that because recruiting will extend beyond the two states, will will follow the
procedures outlined below fo identify and obtain consent for participants and legally
authorized representatives.
Our approach to consent to participate will include two steps. First, initial contact of
potential participants with Down syndrome will always be made through
parents/guardians or organizations/service providers who work with the individuals with
Down syndrome. Persons with Down syndrome will never self identify for the study.
Organizations/Service providers will identify persons eligible to provide valid consent for
potential participants in their system. Parents/Guardians will be presumed to have that
authority if they respond on behalf of their child. Once identified, we will get signed
consent from parents/guardians to ask their children to volunteer to participate in the
project. Participants below the age of majority to consent for research and those who are
deemed ineligible to consent for themselves due to cognitive impairment will be covered
by the signature of parents/guardians. Second, all participants will only be included if
they agree through assent or consent to participate. Participants below the age of 18 (the
youngest age of majority we have found) will be required to provide verbal assent.
Participants above the age of 18 will provide signed Assent/Consent using the document
provided. Participants above the age of majority to consent to participate in research and
participants deemed eligible to sign for themselves by the parents/guardian will be
covered by their own consent document. For the rest, the signature will be treated as
assent to participate, with the consent of the participants’ parents/guardians providing the
necessary informed consent documentation. All rights and considerations due to
participants will be bestowed on the basis of these two signed documents. We will use
the consent forms that have been approved by the IRB already. At this time, we have
identified the age of majority to participate in Clinical Trials research to be 18 years for
most states, with exceptions being Indiana (21), Mississippi (21), Nebraska (19), and
New York (21).
Definitions:
Assent - is defined as a child's or decisionally-challenged individual's affirmative agreement to
participate in research. Mere failure to object should not, absent affirmative agreement, be
construed as assent.
Competence "Technically, a legal term, used to denote capacity to act on one's own behalf;
the ability to understand information presented, to appreciate the consequences of acting (or
not acting) on that information, and to make a choice." [OHRP Institutional Review Board
Guidebook, Chapter VI, Section D]
Permission is defined as the agreement of parent(s) or guardian to the participation of their
child or ward in research or clinical investigation. Permission includes the element of consent
set forth in federal regulations and outlined in the informed consent template included in the
IRB expedited and full review applications.
In Alabama child/children refers to all individuals less than 18 years of age unless the
individual(s) is/are legally emancipated. (See Guidance:  Alabama Law on Children, Minors,
Consent, and Other Research-Related Topics.  Individuals less than 18 years of age who are
not emancipated meet the federal definition for "child" (e.g., Department of Health and Human
Services (DHHS), Food and Drug Administration (FDA), and U.S. Department of Education).
Legally authorized representative (LAR) is an individual who has the authority to make
research participation decisions on behalf of another. Alabama law does not specify who may
make such decisions. UA legal counsel recommends the following in this order of preference:
A legally appointed guardian, a health care proxy or person authorized to make medical
decisions in conjunction with a durable power of attorney, a spouse, an adult child, next of kin,
or a person or agency acting in loco parentis.
NOTE:  Consent from a legally authorized representative involves all the ethical and
regulatory concerns that apply to consent from the prospective participant.

Page 30 of 47
 
---------------------------------------------------------------------------------------------
* * * Subject Population(p) * * *
Research Involving Prisoners
NOTE:  Investigators, please include this information with the e-Protocol application if your research involves
prisoners. This includes studies of known prisoners and studies recruiting participants at risk of becoming
involuntary prisoners, such as participants with histories of substance abuse. Remember that persons
involuntarily committed to mental health facilities (Taylor Hardin Secure Mental Health Facility, Mary Starke
Harper, etc.) by the courts are also prisoners.
If participants unexpectedly become prisoners, go directly to SECTION FOUR of this form.
If your research involves prisoners with more than one vulnerability (i.e., prisoners who are also children or
pregnant, are involuntarily committed to mental health facilities), attach the supplementary form for that
vulnerable population as well.
Regardless of the category of your research, be sure that your application makes clear why the research must be
done on prisoners.
Indicate the category that best represents your research by checking the applicable box below, and explain in the
space provided for that category why your research meets the criteria.
Note: For research involving prisoners, the definition of minimal risk refers to the probability
and magnitude of physical or psychological harm that is normally encountered in the daily
lives, or in the routine medical, dental or psychological examination of healthy persons.
Category 1  (45 CFR 46.306(a)(2)(i))
My research involves the study of possible causes, effects, processes of incarceration,
and of criminal behavior. (Processes of incarceration can be interpreted broadly to
include substance abuse research, half-way houses, counseling techniques, criminal
behavior, etc.)
Justify how the research presents no more than minimal risk and no more than inconvenience to the
participants:
Category 2  (45 CFR 46.306(a)(2)(ii))
My research involves the study of prisons as institutional structures, or of prisoners as
incarcerated persons. (This category is usually used fairly narrowly as when looking at
prisoner diet and conditions of prison life.)
Justify how the research presents no more than minimal risk and no more than inconvenience to the
participants
Category 3  (45 CFR 46.306(a)(2)(iii))
My research involves the study of conditions particularly affecting prisoners as a class.
(This category is less frequently used than the previous ones and refers to such
research as vaccine trials, research on hepatitis, and social and psychological problems
such as alcoholism, drug addiction, and sexual assaults.  Minimal risk studies should not
go under this category.) For DHHS-funded research, OHRP has consulted with
appropriate experts including experts in penology, medicine, and ethics, and published
notice, in the Federal Register, of its intent to approve such research.
Note: Contact the Office of Research Compliance at (205) (348-8461 for more
information
Explain what condition(s) will be studied and provide rationale for each:
Category 4  (45 CFR 46.306(a)(2)(iv))
My research involves the study of practices, both innovative and accepted, which have
the intent and reasonable probability of improving the health or well-being of the
participant. (Note:  It is rare for research involving placebo or control groups to fall in this
category because of the difficulty in justifying improvement of the health or well-being of

Page 31 of 47
 
the participant being given placebo or in a control group.)  For DHHS-funded research
which requires the assignment of prisoners in a manner consistent with protocols
approved by the IRB to control groups which may not benefit from the research, the
study may proceed only after OHRP has consulted with appropriate experts, including
experts in penology, medicine, and ethics, and published notice, in the Federal Register,
of its intent to approve such research.
Note:  Contact the Office of Research Compliance at (205) 348-8461 for more
information.
Explain the research practices that will be used in this study and how they are intended to improve the
health and well-being of the participants:
Section 2.  [45 CFR 46.305]
Note: When an IRB is reviewing a protocol in which a prisoner will be a participant, the IRB
must find and document justification that six additional conditions are met. Describe in the
space provided how each condition applies to your research.
1.
Advantages acquired through participation in the research, when compared to the
prisoners' current situation, are not so great that they impair their ability to weigh risks.
Describe the possible advantages that can be expected for prisoner participants:
2.
Risks are the same as those that would be accepted by non-prisoners.
Describe the possible risks that can be expected for prisoner participants and justify that they are the
same as for non-prisoners:
3.
Procedures for selection are fair to all prisoners and are immune from intervention by
prison authorities in prisons; control participants must be randomly selected.
a)
Describe how prisoners will be selected for participation:
b)
Describe what measures will be taken to prevent intervention by prison authorities in the selection
process:
4.
Parole boards cannot take into consideration a prisoner's participation in research.
Informed consent must state participation will not affect length of sentence or parole.
5.
For studies that require follow-up, provisions are made including consideration for the
length of individual sentences; informed consent must reflect provisions for follow-up.
Describe what provisions have been made for follow-up and how this information will be relayed to the
prisoner participants:
6.
Information about the study is presented in a language understandable to prisoners.
Describe what efforts have been made to present information about the study in a
language   that is understandable to the prisoner population. This may mean a non-
English language or an appropriate reading level in whatever language the prisoner
uses.:
Section 3. Only complete if applicable:  Epidemiologic Research Involving Prisoners and Funded by the
Department of Health and Human Services (DHHS)
Note: Effective June 20, 2003, DHHS adopted policy that allows waiver of the requirement for

Page 32 of 47
 
documenting applicability of a 45 CFR 306(a)(2) category (as found in Section 1 of this form)
for certain epidemiologic research involving prisoners.  This waiver applies to DHHS
conducted or supported epidemiologic research on prisoners that presents no more than
minimal risk and no more than inconvenience to the prisoner-participants.
Check the box below if your research meets the listed criteria, then provide justification in the
space provided.
1.
My research is funded by HHS and I request a waiver for meeting the category
conditions under Section 1 of this form.
2.
My research involves epidemiologic research intended to describe the
prevalence/incidence of a disease by identifying all cases, or to study potential risk
factor associations for a disease; and
3.
Prisoners are not the sole focus of my research.
Justify how the research presents no more than minimal risk and no more than inconvenience to the participants:
Section 4.   Complete if applicable:
Prisoners are not the targeted population
Note: Although prisoners may not be the target population for your research, a participant
could become a prisoner during the course of the study (particularly if studying a subject
population at high-risk of incarceration).
Note: If you did not receive IRB approval for involvement of prisoners, and a participant
becomes a prisoner during the study, all research interactions and interventions with, and
obtaining identifiable private information about, the now-incarcerated participant must cease
until IRB approval has been issued for their continuation in the research.  If you need IRB
approval for a prisoner participant to continue participation in your research, select and
complete the applicable category from Section 1, complete section 2 and this section, then
submit for IRB review.
In special circumstances in which the Principal Investigator asserts that it is in the best interest
of the participant to remain in the research study while incarcerated, the IRB Chairperson may
determine that the participant may continue to participate in the research prior to satisfying the
requirements of Subpart C.  However, subsequent IRB review and approval of this completed
form, documenting that the requirements of Subpart C are met, is required.
Prisoners are not a target population for my research, but a participant became a prisoner
during the study and I am seeking IRB approval so the participant can continue
participation in the research.
Explain the importance of continuing to intervene, interact, or collect identifiable private information during
the participant's incarceration:
Note: Prisoner: An individual involuntarily confined in a penal institution, including persons: (1)
sentenced under a criminal or civil statue; (2) detained pending arraignment, trial, or
sentencing; and (3) detained in other facilities (e.g., for drug detoxification or treatment of
alcoholism,) under statutes or commitment procedures providing such alternatives to criminal
prosecution or incarceration in a penal institution [45 CFR 46.303(c)]. Note:  Persons on
Probation and parole are usually NOT considered to be prisoners.
If you will receive or are seeking Department of Health and Human Services (HHS) funding for
this study, a certification letter must be submitted to the Office for Human Research
Protections (OHRP). The research cannot be initiated until OHRP issues approval. The Office
of Research Compliance (ORC) will prepare and submit the certification report to OHRP.
Contact the Director for the Office of Research Compliance at 205-348-8461 8641 for more
information.

Page 33 of 47
 
---------------------------------------------------------------------------------------------
* * * Risks * * *
8.
Risks
There is no research that can be considered totally risk free (e.g., a potential risk of breach of
confidentiality). Therefore, when describing the risk, the lowest level of risk is "no more than
minimal risk".
a)
For the following categories include a scientific estimate of the frequency, severity, and reversibility of
potential risks. Wherever possible, include statistical incidence of complications and the mortality rate of
proposed procedures. Where there has been insufficient time to accumulate significant data on risk,a
statement to this effect should be included. (In describing these risks in the consent form to the participant,
it is helpful to use comparisons which are meaningful to persons unfamiliar with medical terminology).
Address any risks related to (input N/A if not applicable):
1.
Use of investigational drugs. Please include the clinical adverse events (AEs) associated
with each of the drugs with an indication of frequency, severity and reversibility. This
information can often be found in the Investigator(s) brochure. NOTE: Include any likely
adverse effects associated with placebos or washout periods that participants may
experience while in the study.
N/A
2.
Use of investigational devices. Please include the clinical adverse events (AEs)
associated with each of the devices with an indication of frequency, severity and
reversibility. This information can often be found in the Investigator(s) brochure. NOTE:
Include any likely adverse effects associated with procedures that participants may
experience while in the study.
N/a
3.
Use of FDA approved drugs, reagents, chemicals, or biologic products. Please include
the clinical adverse events (AEs) associated with each of the drugs with an indication of
frequency, severity and reversibility. This information can often be found in the package
insert provided by the manufacturer. NOTE: Include any likely adverse effects associated
with placebos or washout periods that participants may experience while in the study.
N/A
4.
Use of FDA approved devices. Please include the clinical adverse events (AEs)
associated with each of the devices with an indication of frequency, severity and
reversibility. This information can often be found in the Investigator(s) brochure. NOTE:
Include any likely adverse effects associated with procedures that participants may
experience while in the study.
N/A
5.
Describe any risks related to performing study procedures. Please include all
investigational, non-investigational, and non-invasive procedures (e.g., surgery, blood
draws, treadmill tests).
N/A
6.
Describe any risks related to the use of radioisotopes/radiation-producing machines (e.g.,
X-rays, CT scans, fluoroscopy).
N/A
7.
For clinical studies (of a drug, vaccine, device or treatment), describe any alternative
procedure(s) or course(s) of treatment. List important risks and benefits of these
alternatives in order to compare to study procedure(s) or course(s) of treatment. This
information MUST be included here. Any standard treatment that is being withheld must
be disclosed and the information must be included in the consent form.
N/A

Page 34 of 47
 
8a. Describe any other physical, psychological, social or legal risks the participant may
experience.
Mild boredom/fatigue is possible but unlikely. Sessions are relatively short and involve
game-like activities.
8b. Data Safety Monitoring
Is there a Data Monitoring Committee (DMC) or Board (DSMB)?
N
If yes, describe its role, if it is independent of the sponsor or research team, the make-up
of the Board and their qualifications, and how often the Board will meet.
If no, please justify why not.
The nature of the data do not require a DMC.
Is there a Data Safety Monitoring Plan (DSMP)?
Y
If yes, describe the data and safety monitoring plan developed to ensure the safety of
participants and the validity and integrity of research data. Monitoring should be
commensurate with risks and with the size and complexity of the trials. As such, state
that SAEs will be reviewed by a qualified MD in real time and indicate how often
aggregate data will be reviewed for safety trends.
Rationale. The Data Safety and Monitoring Plan (DSMP) for our intervention research
on Assessing the Malleability of Spatial Abilities in Downs Syndrome has two specific
goals (1) to ensure the confidentiality of all data, and (2) to ensure that participant
experiences are positive by minimizing fatigue and frustration.
Design of DSMP. Prior to the initiation of testing, Drs. Merrill and Yang will train
Graduate and Undergraduate assistants on monitoring participants for expressions of
fatigue and frustration. They will be providing strategies for alleviating any difficulties
that may arise. On-going monitoring of potential problems will take place during our bi-
weekly meetings, with Montclair State and University of Alabama communicating via
Skype or Facetime. We will discuss the number of participants tested over the two week
period, ensure that identifying information is not stored with any data, and that data has
been recorded without identifiers in UA Box (a secure cloud storage service for UA
faculty). Data will be shared between sites via UA Box, to which both PIs have access
(Dr. Yang is a former Graduate student and still has UA Access). All information that
can be used to identify participants will be locked in the offices of Dr. Merrill and Dr.
Yang. We will also evaluate whether or not participants have exhibited any fatigue and
frustration during the testing period and review how that was resolved. If necessary,
additional procedures to ensure that participants get adequate breaks and refreshments
during each session will be implemented. Any additional and unforeseen adverse
events will be discussed and plans will be implemented to prevent future difficulties.
Reporting of Adverse Events. Research personnel will be told to report all suspected
adverse events immediately to Dr. Yang and Dr. Merrill. Dr. Merrill will report these
events to the research team and the appropriate IRB personnel. All adverse events will
be discussed at the next bi-weekly meeting of the research team. The PIs will amend
the research protocol if a serious adverse event occurs that is found to be the result of
the protocol.
If no, please justify why not.
---------------------------------------------------------------------------------------------
* * * Benefits/Alternatives, Procedures to Maintain Confidentiality * * *
9.
Benefits/Alternatives
a)
Benefits. Describe the potential benefit(s) to be gained by the participants and how the results of the study
may benefit future participants and/or society in general. Indicate if there is no direct benefit to the

Page 35 of 47
 
may benefit future participants and/or society in general. Indicate if there is no direct benefit to the
participants.
Participants may benefit from improved spatial abilities that can positively impact
performance in everyday activities.
b)
Alternatives. Describe any alternative treatments and procedures available to the participants should they
choose not to participate in the study. If no such alternatives exist, please state that the alternative is
nonparticipation. For some studies, such as record reviews, a description of alternatives would not be
applicable.
The alternative is nonparticipation.
10.
Procedures to Maintain Confidentiality
Federal regulations require that study data and consent documents be kept for a minimum of
three (3) years, and HIPAA documents be kept for a minimum of six (6) years after the
completion of the study by the PI. For longitudinal or sponsored projects, the PI may be
required to keep the data and documents for a longer time period.
Data Security
Please indicate how information will be secured. All information must be stored using at least
two of the following safeguards and must be kept in accordance with the University of
Alabama Information Security Policies. (If you are using both electronic data and hard copy
data, you will need two safeguards for each type).
a)
Electronic Data: (mark all that apply - at least 2 - or indicate not applicable)
Not applicable
X Password access
X Coded, with a master list kept as a hardcopy or on a secure network (confidential)
Data collected anonymously
Secure network (e.g., firewall)
X Data are de-identified by PI or research team
Other
Please specify:
b)
Hardcopy Data: (mark all that apply - at least 2 - or indicate not applicable))
Not applicable
Locked suite
X Locked office
Locked file cabinet
X Coded, with a master list secured and kept separately (confidential)
Data collected anonymously
24 hour personnel supervision
Data are de-identified by PI or research team
Other
Please specify:
c)
Describe measures employed to protect the identity of the participants, their responses,
and any data that you obtain from private records (e.g., identifiers will be stripped so data
cannot be linked to participants, or code numbers will be used, etc.). If data will be coded,
specify the procedures for coding the data so that confidentiality of individual participants
is protected. If you will keep a master list linking study codes to participant identifiers,
explain why this is necessary, how and where you will secure the master list, and how

Page 36 of 47
 
long it will be kept.
All data will be identified by number rather than name. The PI at each site will keep a
master list of names and number codes that will be in a locked office until data collection
is complete for each participant. After that time, all identifiers will be removed and it will
be impossible to link the data to any specific participant. Data will be shared between
sites via UA Box, to which both PIs have access (Dr. Yang is a former Graduate student
and still has UA Access).
d)
If data or specimens are being shared outside of the research team, indicate who will
receive the material and specifically what they will receive (data or specimens).
N/A
e)
If samples or data will be provided from an outside source, indicate whether you will have
access to identifiers, and, if so, how identifiable information is protected. Please provide a
letter from the appropriate persons indicating that data will be provided in a de-identified
manner.
N/A
f)
If data will be collected via e-mail or the internet, how will anonymity or confidentiality be
protected? Describe how data will be protected during electronic transmission and how
data will be recorded (i.e., will internet protocol (IP) address and/or e-mail addresses be
removed from data?).
g)
If you will be audio/video recording or photographing participants, provide a rationale for
recording/photographing. Describe confidentiality procedures, including the final
disposition of the recordings/photos (destruction, archiving, etc.) and a reasonable
timeline by which this disposition will occur.
---------------------------------------------------------------------------------------------
* * *  Potential Conflict of Interest * * *
11)
Potential Conflict of Interest
Federal regulations and UA policy require all investigators to disclose their significant financial
interests to allow a review of potential conflicts of interest. If a potential conflict of interest is
identified, a formal plan must be developed and implemented to manage, reduce, or eliminate
the conflict.
Examples of significant financial interests include receipt of income, honoraria, and stock or
stock options from a public or private entity sponsoring the research. They may also include a
consulting arrangement or membership on an advisory board of the entity.  Significant
financial interests are reported on the UA Statement of Financial Interest.
All members of the research team who are involved in the design, conduct, or reporting of
research (i.e., senior/key personnel) should have a current Statement of Financial Interest and
conflict of interest training on file prior to submitting the IRB protocol.  Please refer to the
Office for Research Compliance website for additional information regarding the financial
conflict of interest requirements, as well as links to the disclosure form and training at
(http://osp.ua.edu/site/RC_CoI.html).
The Statement of Financial Interest must be submitted annually and within 30 days of
discovering or acquiring a new or increased financial interest. Conflict of interest training must
be completed once every four years.
If such a relationship as described above exists between a member of the research team and
the sponsor of the research, the investigator is also required to disclose this relationship and
identify the entity involved on the informed consent form.
 For questions regarding Conflict of Interest consult the   Conflict of Interest in Research

Page 37 of 47
 
Policy.
Check one of the following:
1)
X No Financial Interest or Financial interest less than or equal to $5K
2)
Financial Interest exceeding $5K but not exceeding $25K, and/or more than 5 percent
equity interest in aggregate
3)
Financial Interest exceeding $25K
Check all those that apply:
Consulting
Speaking Fees or Honoraria
Gifts
Patent
Copyright
Licensing agreement or royalty income
Equity interests, (including stock, stock options, warrants, partnership or equitable
ownership interests), or serving on a scientific advisory board or board of directors
Other fees/compensation
Describe financial interests(s) and indicate specific amounts for each subcategory
checked. Be sure to describe how these financial interests relate to the protocol being
submitted.
Note to Investigator(s) Reporting a Potential Conflict of Interest
Investigator(s) must have:
1)
Current, up-to-date Conflict of Interest Disclosure Form on file with the University of
Alabama Conflict of Interest Committee (COIC) that describes any financial relationship
indicated above.
.
This information must be disclosed on the University of Alabama confidential Conflict of
Interest Disclosure Form for review by the COIC before accruing research participants in
this study. If your current Disclosure Form does not contain this information, you are
required to submit an updated Disclosure Form to the COIC.
2)
Financial disclosure statement incorporated into the consent document. Please see
Model Consent for suggested language.
3)
You may not begin your study until your disclosure form has been reviewed and any
required management plan has been approved by the COIC.
Does any member of the study team, members' spouses, or members' dependent children have any
significant financial interests related to the work to be conducted as part of the above-referenced project?
N
 
Name of Personnel with Financial Conflict of Interest
Other research staff that may have a conflict. Please specify below.
Any member of the study team who answers in the affirmative must be listed in the box below.
A staff person will contact any researcher listed above to obtain additional information
regarding the specific financial interest(s).
I certify that all members of the study team have answered the financial interests question and only those
individuals listed in the box above have disclosed any financial interest related to this study.
Y

Page 38 of 47
 
---------------------------------------------------------------------------------------------
* * * Informed Consent * * *
12
Informed Consent
Federal regulations require that informed consent be obtained from individuals prior to their participation in
research unless the IRB grants a waiver of consent. Answer the questions, below, then click Add to provide the
necessary consent documents and information regarding participant consent. Multiple consents/waivers may be
added, but they must be uploaded one at a time.
NOTE: You may refer to the University of Alabama IRB Guidance for Obtaining Informed
Consent for considerations regarding the consent/assent process.
State N/A if not applicable.
1)
How is consent being obtained? When and where will the discussion take place?
Parents/guardians will be sent consent forms and asked to return them to the PI at the
appropriate location. Adults participants will be consented at the start of the study. All
adult participants with Down syndrome will be read the consent aloud.
2)
Explain how risks, benefits, and alternatives will be discussed.
They will be read on the consent. The consent will be read aloud to participants with
down syndrome. Questions will be answered if any arise.
Informed Consent
Title
Consent Type
Attached Date
Remote Testing - Adult
Participant Consent
Consent
11/14/2020
Parent Consent to Record
Consent
11/14/2020
Adult Participant Consent to
Record
Consent
02/09/2021
Consent for Scheduling
Flexibility
Addendum Consent
05/15/2021
Remote Testing - Parent
Consent - New Control
Consent
08/09/2022
---------------------------------------------------------------------------------------------
* * * Assent * * *
13
Assent
Complete this section if your study includes minors. An assent document should be used if participants are 6 to
18 years of age. The Assent Form Template provides guidelines for writing assent documents.
1)
Will minors be asked to give assent? If not, please justify.
Yes
Note: For studies that require a discussion about reproductive risks, note that the conversation
with the minor should take place separately from the parents. Also, if a minor will reach
adulthood (18 in Missouri) during the course of the study, they will need to be asked to
consent as an adult at that time to continue in the study.
Assent Documents
Title
Upload assent document
Attached Date
Basic Assent Script
Basic Script for Assent
10.10.2019
10/10/2019
Assent to Record Sessions
Assent to Record Child
Participant
02/09/2021

Page 39 of 47
 
---------------------------------------------------------------------------------------------
* * * HIPAA * * *
14
HIPAA
Studies that receive or create protected health information (PHI) are subject to HIPAA
regulations. PHI is health information with one or more personal identifiers. For more
information see: http://www.ua.edu/research/index.html
If you are working with UMC, then a separate IRB approval is required. This must be obtained
prior to IRB submission and attached.
1)
Will health information be accessed, received or collected?
X No health information. HIPAA does not apply.
Yes (continue to question 2).
2)
Which personal identifiers will be accessed, received or collected?
No identifiers. I certify that no identifiers from the list below will be received or
collected and linked to health information. HIPAA does not apply (skip remainder of
page).
Names
Social Security numbers
Telephone numbers
Linkable code or any other unique identifying number (note this does not mean the
unique code assigned by the Investigator(s) to code the research data)
All geographic subdivisions smaller than a State, including street address, city,
county, precinct, zip code, and their equivalent geocodes, except for the initial three
digits of a zip code, if, according to the current publicly available data from the Bureau
of the Census: (1) The geographic unit formed by combining all zip codes with the
same three initial digits contains more than 20,000 people; and (2) The initial three
digits of a zip code for all such geographic units containing 20,000 or fewer people is
changed to 000
All elements of dates (except year) for dates directly related to an individual, including
birth date, admission date, discharge date, date of death; and all ages over 89 and all
elements of dates (including year) indicative of such age, except that such ages and
elements may be aggregated into a single category of age 90 or older
Fax numbers
Electronic mail addresses
Medical record numbers
Health plan beneficiary numbers
Account numbers
Certificate/license numbers
Vehicle identifiers and serial numbers, including license plate numbers
Device identifiers and serial numbers
Web Universal Resource Locations (URLs)
Internet Protocol (IP) address numbers
Biometric identifiers, including finger and voice prints
Full face photographic images and any comparable images
If you are receiving or collecting health information and at least one personal identifier, HIPAA applies to your
study. Please continue to complete the sections, below.
3)
Sources of Protected Health Information:

Page 40 of 47
 
Hospital/medical records for in or out patients
Physician/clinic records
Laboratory, pathology and/or radiology results
Biological samples
Interviews or questionnaires/health histories
Mental health records
Data previously collected for research purposes
Billing records
Other
 Please describe:
4)
If data will be shared outside the research team and the study involves PHI indicate how the research team
will share the information. Contact the University of Alabama Privacy Officer for guidance on the proper
procedures for sharing of protected health information. http://hipaa.ua.edu/
Not applicable (continue to question 5).
Only linkable code that can link data to the identity of the participant. A code access
agreement or business associate agreement may be needed when data are shared
with other non-University of Alabama entities. If necessary, the agreement can be
added and uploaded in item #5, below.
Limited identifiers: Zip codes, dates of birth, or other dates only. The study qualifies
as a Limited Data Set. A data use agreement may be needed when data are shared
with other non-AlaUniversity of Alabamatities. If necessary, the agreement can be
added and uploaded in item #5, below.
With unlimited identifiers. The consent document and HIPAA Authorization form must
describe how the information will be disclosed.
5)
A HIPAA Authorization Form or Waiver of HIPAA Authorization is required for this study. Use the table
below to add HIPAA Documents for your study. If you are accessing medical records, or other health
records that include PHI, you must complete a waiver of HIPAA authorization.
---------------------------------------------------------------------------------------------
* * * Attachments * * *
15)
Attachments
In this section, please upload additional documents associated with your protocol. Failure to attach files
associated with the protocol may result in the protocol being returned to you.
Possible documents for this protocol could include:
Bibliography
Cooperating Institution's IRB Approval
Data Collection Sheet
Debriefing Script
Device Information/Documentation
Grant Proposal/Sub-Contract
Human Participants Training Certificate/Proof of Training
IND Application Letter
Information Sheet/Brochure
Interview/Focus Group Questions
Investigator's Brochure
Letter of Agreement/Cooperation

Page 41 of 47
 
Package Insert
Patient Diary Form
Phone Script
Questionnaire/Survey
Recruitment Material (e.g., flyers, ads, e-mail text)
Recruitment Statement (if there is no waiver of written consent)
Scientific/PPC Review
Sponsor's Protocol
Sponsor's Protocol Amendment
Study Design Chart/Table
Waiver Request
Other files associated with the protocol (most standard formats accepted: pdf, jpg, tif, mp3,
wmv, etc.)
To update or revise any attachments, please delete the existing attachment and upload the revised document to
replace it.
Document Type
Document Name
Attached Date
Submitted Date
Grant Proposal/Sub-
Contract
Assessing
Malleability
08/15/2019
08/15/2019
Other
Ltr UofA IAA Yang
09/10/2019
09/10/2019
Other
Merrill app w rev
09/27/2019
09/27/2019
Other
IRB Cover Letter -
Response to Full
Board Review
10/07/2019
10/07/2019
Other
Merrill 19-016
10/23/2019
10/23/2019
Other
Addendum Cover
Letter
07/23/2020
07/23/2020
Cooperating
Institution's IRB
Approval
Merrill IRB
Authorization
Agreement MSU
UofA
07/23/2020
07/23/2020
Other
Merrill 19-016 A
07/27/2020
07/27/2020
Other
Merrill fully executed
agreement
07/27/2020
07/27/2020
Other
Merrill app w rev
Sept 2020
09/22/2020
09/22/2020
Other
Merrill 19-016-R1 (eP
19-08-2644)
10/30/2020
10/30/2020
Other
Addendum 2 Cover
Letter
11/14/2020
11/14/2020
Recruitment Material
(e.g., flyers, ads, e-
mail text)
Contact Letter for
Parents Identified by
Schools or Service
Providers Malleability
11/14/2020
11/14/2020
Other
Merrill app w rev Dec
2020
12/18/2020
12/18/2020

Page 42 of 47
 
Other
Merrill Dec 2020 app
w rev
12/18/2020
12/18/2020
Other
Merrill 19-016-R1 A
FB approval
03/04/2021
03/04/2021
Other
Merrill 19-016-R1 B
04/12/2021
04/12/2021
Recruitment Material
(e.g., flyers, ads, e-
mail text)
Merrill Research
Page
05/15/2021
05/15/2021
Letter of
Agreement/Cooperati
on
Michelle Darabaris
Approval
05/15/2021
05/15/2021
Recruitment Material
(e.g., flyers, ads, e-
mail text)
Strategic
Communications
06/08/2021
06/08/2021
Other
Merrill 19-016-R1 C
06/21/2021
06/21/2021
Other
Merrill approval 19-
016-R2
09/17/2021
09/17/2021
Other
Merrill 19-016-R3
08/22/2022
08/22/2022
Recruitment Material
(e.g., flyers, ads, e-
mail text)
UnStamped DS Kids
Flyer Lab
07/14/2023
07/14/2023
Recruitment Material
(e.g., flyers, ads, e-
mail text)
UnStamped Typical
Kids Flyer Lab
07/14/2023
07/14/2023
IRB Approval
Merrill 19-016-
R4_19-08-
2644_Approval
08/21/2023
08/21/2023
IRB Approval
Merrill 19-016-R4-A
Approval
09/27/2023
07/15/2024
Human Subjects
Training
Certificate/Proof of
Training
citiCompletionCertific
ate_Jennifer Yang
08/07/2024
08/07/2024
Human Subjects
Training
Certificate/Proof of
Training
Stephanie Grinshpun
CITI
08/07/2024
08/07/2024
Human Subjects
Training
Certificate/Proof of
Training
citiCompletionCertific
ate_Zakrzewski
08/07/2024
08/07/2024
Human Subjects
Training
Certificate/Proof of
Training
CITI Program
Completion
Certificate 61800939
08/07/2024
08/07/2024
IRB Approval
Merrill_19-016-
R5_19-08-
2644_Approval
08/08/2024
---------------------------------------------------------------------------------------------
* * * PI Obligations * * *

Page 43 of 47
 
PI Obligations
By clicking the box below, you indicate that you accept responsibility for and will follow the
ethical guidelines.
1)
Have you completed the annual Statement of Financial Interest (i.e., disclosure)?
Y
NOTE: An annual disclosure must be completed by all faculty, staff, and students who are
identified as senior/key personnel receiving federal funding for research.  The disclosure can
be completed online at https://www.formstack.com/forms/index.php?1338617-e6Kw9EILFS.
2)
Have your financial interests changed significantly since you completed the annual
disclosure form?
N
According to the UA policy on conflict of interest, it is the PI's responsibility to inform co-
investigators, staff, or students involved in the design, conduct, or reporting of federally
sponsored research of their requirement to complete the Statement of Financial Interest.
X I accept this responsibility.
By submitting this form, the PRINCIPAL INVESTIGATOR certifies that he/she has read the
UA policy on conflict of interest and has a current Statement of Financial Interest on file.  In
addition, the PI certifies that, to the best of his/her knowledge, no person working on this
project at UA has a conflict of interest or, if a conflict of interest does exist, an appropriate
management plan is in place.
X The Principal Investigator has read and agrees to abide by the above obligations.
The Department Chair has read and agrees to abide by the above obligations.
The Faculty Sponsor / Mentor has read and agrees to abide by the above obligations.
---------------------------------------------------------------------------------------------
* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
08/08/2024
CONTINUING
REVIEW 5 FORM
APPROVED
Y
Y
08/08/2024
CONTINUING
REVIEW 5 FORM
REVIEWER(S)
ASSIGNED
08/07/2024
CONTINUING
REVIEW 5 FORM
RESUBMITTED
Y
07/22/2024
CONTINUING
REVIEW 5 FORM
RETURNED
07/15/2024
CONTINUING
REVIEW 5 FORM
SUBMITTED
Y
07/15/2024
CONTINUING
REVIEW 5 FORM
CREATED
09/27/2023
AMENDMENT 6
FORM APPROVED
Y
Y

Page 44 of 47
 
09/27/2023
AMENDMENT 6
FORM
REVIEWER(S)
ASSIGNED
09/27/2023
AMENDMENT 6
FORM PANEL
REASSIGNED
09/15/2023
AMENDMENT 6
FORM SUBMITTED
Y
09/15/2023
AMENDMENT 6
FORM CREATED
08/21/2023
CONTINUING
REVIEW 4 FORM
APPROVED
Y
Y
08/10/2023
CONTINUING
REVIEW 4 FORM
REVIEWER(S)
ASSIGNED
07/14/2023
CONTINUING
REVIEW 4 FORM
SUBMITTED
Y
07/12/2023
CONTINUING
REVIEW 4 FORM
CREATED
08/22/2022
CONTINUING
REVIEW 3 FORM
APPROVED
Y
Y
08/11/2022
CONTINUING
REVIEW 3 FORM
REVIEWER(S)
ASSIGNED
08/10/2022
CONTINUING
REVIEW 3 FORM
SUBMITTED
Y
08/09/2022
CONTINUING
REVIEW 3 FORM
CREATED
08/09/2022
AMENDMENT 5
FORM DELETED
08/09/2022
REPORT 2 FORM
CREATED
07/14/2022
AMENDMENT 5
FORM RETURNED
07/14/2022
AMENDMENT 5
FORM SUBMITTED
Y
07/14/2022
AMENDMENT 5
FORM CREATED
09/17/2021
CONTINUING
REVIEW 2 FORM
APPROVED
Y
Y

Page 45 of 47
 
09/09/2021
CONTINUING
REVIEW 2 FORM
REVIEWER(S)
ASSIGNED
08/11/2021
CONTINUING
REVIEW 2 FORM
SUBMITTED
Y
08/11/2021
CONTINUING
REVIEW 2 FORM
CREATED
06/21/2021
AMENDMENT 4
FORM APPROVED
Y
Y
06/17/2021
AMENDMENT 4
FORM
REVIEWER(S)
ASSIGNED
06/10/2021
AMENDMENT 4
FORM
REVIEWER(S)
ASSIGNED
06/08/2021
AMENDMENT 4
FORM
RESUBMITTED
Y
06/02/2021
AMENDMENT 4
FORM RETURNED
05/15/2021
AMENDMENT 4
FORM SUBMITTED
Y
05/15/2021
AMENDMENT 4
FORM CREATED
04/12/2021
AMENDMENT 3
FORM APPROVED
Y
Y
04/08/2021
AMENDMENT 3
FORM
REVIEWER(S)
ASSIGNED
04/08/2021
AMENDMENT 3
FORM
RESUBMITTED
Y
04/07/2021
AMENDMENT 3
FORM RETURNED
03/22/2021
AMENDMENT 3
FORM SUBMITTED
Y
03/22/2021
AMENDMENT 3
FORM CREATED
03/04/2021
AMENDMENT 2
FORM APPROVED
Y
Y
03/04/2021
REPORT 1 FORM
CREATED

Page 46 of 47
 
12/18/2020
AMENDMENT 2
FORM
REVIEWER(S)
ASSIGNED
12/10/2020
AMENDMENT 2
FORM
REVIEWER(S)
ASSIGNED
12/02/2020
AMENDMENT 2
FORM PANEL
MANAGER REVIEW
11/14/2020
AMENDMENT 2
FORM SUBMITTED
Y
11/14/2020
AMENDMENT 2
FORM CREATED
10/30/2020
CONTINUING
REVIEW 1 FORM
APPROVED
Y
Y
09/22/2020
CONTINUING
REVIEW 1 FORM
REVIEWER(S)
ASSIGNED
09/10/2020
CONTINUING
REVIEW 1 FORM
REVIEWER(S)
ASSIGNED
09/02/2020
CONTINUING
REVIEW 1 FORM
PANEL MANAGER
REVIEW
08/15/2020
CONTINUING
REVIEW 1 FORM
SUBMITTED
Y
08/15/2020
CONTINUING
REVIEW 1 FORM
CREATED
07/27/2020
AMENDMENT 1
FORM APPROVED
Y
Y
07/23/2020
AMENDMENT 1
FORM
REVIEWER(S)
ASSIGNED
07/23/2020
AMENDMENT 1
FORM SUBMITTED
Y
07/23/2020
AMENDMENT 1
FORM CREATED
10/23/2019
NEW FORM
APPROVED
Y
Y
10/07/2019
NEW FORM
REVIEWER(S)
ASSIGNED

Page 47 of 47
 
09/27/2019
NEW FORM
REVIEWER(S)
ASSIGNED
09/13/2019
NEW FORM
REVIEWER(S)
ASSIGNED
09/12/2019
NEW FORM
REVIEWER(S)
ASSIGNED
09/12/2019
NEW FORM PANEL
ASSIGNED
09/10/2019
NEW FORM
RESUBMITTED
Y
08/20/2019
NEW FORM
RETURNED
08/15/2019
NEW FORM
SUBMITTED
Y
08/14/2019
NEW FORM
CREATED