To Compare the Effectiveness of 3 Different Types of Lens and Lens Coating in Eliminating Symptoms for Children With Prolonged Visual Symptoms Due to a Concussion.
Phase: NA
Conditions: Concussion, Mild, Convergence Insufficiency, Accommodation; Insufficiency
Sponsor: University of Alabama at Birmingham

  
<Spectacle lenses in concussed kids> 
 
Principal Investigator: <Katherine Weise> 
Sponsor: <UAB> 
National Clinical Trial (NCT) Identified Number:  <03123822> 
 
Version Number:  v1.0 
<02 04 2022> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schedule of Activities (SoA) ............................................................................................................... 1 
2 
INTRODUCTION ............................................................................................................................................ 2 
2.1 
Study Rationale .................................................................................................................................... 2 
2.2 
Background........................................................................................................................................... 2 
2.3 
Risk/Benefit Assessment .................................................................................................................... 2 
2.3.1 
Known Potential Risks ..................................................................................................... 3 
2.3.2 
Known Potential Benefits ................................................................................................ 3 
3 
STUDY DESIGN ............................................................................................................................................. 3 
3.1 
Overall Design ...................................................................................................................................... 3 
3.2 
End of Study Definition ....................................................................................................................... 3 
4 
STUDY POPULATION .................................................................................................................................. 4 
4.1 
Inclusion Criteria .................................................................................................................................. 4 
4.2 
Exclusion Criteria ................................................................................................................................. 4 
4.3 
Screen Failures .................................................................................................................................... 4 
4.4 
Strategies for Recruitment and Retention ........................................................................................ 5 
5 
STUDY INTERVENTION .............................................................................................................................. 5 
5.1 
Study Intervention(s) Administration ................................................................................................. 5 
5.1.1 
Study Intervention Description ....................................................................................... 5 
5.1.2 
Dosing and Administration .............................................................................................. 5 
5.2 
Measures to Minimize Bias: Randomization .................................................................................... 5 
5.3 
Study Intervention Compliance .......................................................................................................... 5 
5.4 
Concomitant Therapy .......................................................................................................................... 5 
6 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ...................................................................................................................... 5 
6.1 
Discontinuation of Study Intervention ............................................................................................... 6 
6.2 
Subject Discontinuation/Withdrawal from the Study ....................................................................... 6 
6.3 
Lost to Follow-Up ................................................................................................................................. 6 
7 
STUDY ASSESSMENTS AND PROCEDURES ....................................................................................... 6 
7.1 
STUDY Assessments .......................................................................................................................... 6 
7.2 
Adverse Events and Serious Adverse Events ................................................................................. 6 
7.2.1 
Definition of Adverse Events (AE) ................................................................................. 7 
7.2.2 
Definition of Serious Adverse Events (SAE) ................................................................ 7 
7.2.3 
Classification of an Adverse Event ................................................................................ 7 
7.2.4 
Time Period and Frequency for Event Assessment and Follow-Up ......................... 8 
7.2.5 
Adverse and serious adverse Event Reporting ........................................................... 8 
7.3 
Unanticipated Problems ...................................................................................................................... 9 
7.3.1 
Definition of Unanticipated Problems (UP) ................................................................... 9 
7.3.2 
Unanticipated Problem Reporting .................................................................................. 9 
8 
STATISTICAL CONSIDERATIONS ............................................................................................................ 9 
8.1 
Statistical Hypotheses ......................................................................................................................... 9 
8.2 
Sample Size Determination .............................................................................................................. 10 
8.3 
Statistical Analyses............................................................................................................................ 10 
8.3.1 
General Approach .......................................................................................................... 10 

  
8.3.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 10 
8.3.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 10 
8.3.4 
Safety Analyses .............................................................................................................. 10 
8.3.5 
Baseline Descriptive Statistics ..................................................................................... 10 
9 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 10 
9.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 10 
9.1.1 
Informed Consent Process ........................................................................................... 10 
9.1.2 
Study Discontinuation and Closure ............................................................................. 11 
9.1.3 
Confidentiality and Privacy ........................................................................................... 12 
9.1.4 
Quality Assurance and Quality Control ....................................................................... 12 
9.1.5 
Data Handling and Record Keeping ............................................................................ 12 
9.1.6 
Protocol Deviations ........................................................................................................ 13 
9.1.7 
Conflict of Interest Policy .............................................................................................. 13 
9.2 
Abbreviations ...................................................................................................................................... 14 
10 
REFERENCES ............................................................................................................................................. 15 
 

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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and applicable United States (US) Code of Federal Regulations (CFR). The Principal 
Investigator will assure that no deviation from, or changes to, the protocol will take place without prior 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial subjects. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the local Institutional Review Board (IRB) for review and approval. Approval of both the 
protocol and the consent form must be obtained before any subject is enrolled. Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the study. 
All changes to the consent form will be IRB approved; a determination will be made regarding whether a 
new consent needs to be obtained from subjects who provided consent, using a previously approved 
consent form. 
 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Spectacle lenses in concussed kids  
Study Description: 
Many kids who have sustained a concussion still experience symptoms 
months after the event. This study will examine if certain types of lenses in 
glasses will help alleviate those symptoms.  
Objectives: 
 
Compare symptoms of concussed kids after wearing different types of 
glasses, one of which is a control.   
Endpoints: 
3 month follow up phone call  
Study Population: 
9-17 year olds who have sustained a concussion and are symptomatic 
Phase: 
3 
Description of Study 
Intervention: 
Different types of glasses lenses that are already commercially available 
and are used routinely in concussion patient.  
Study Duration: 
2-3 years, largely dependent on ability to recruit subjects   
Subject Duration: 
3 months 
 
 
1.2 
SCHEDULE OF ACTIVITIES (SOA) 
 
1. Participants are recruited through routine eye exams at concussion clinic  
2. If a patient is eligible for study, an investigator will reach out to the patient at that time to 
present patient with the opportunity to enroll in the study. The patient has 1 week from that 
date to decide.  
3. Once consents are signed and subject is officially enrolled, they will be randomized into 1 of 3 
possible lens options. 
4. Investigators will then order the lenses from the supplier to then be fit in patient’s glasses  
5. Dispense of glasses to participant (timing will vary due to dependence on supplier). Repeat 
concussion survey at dispense.   

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6. Masked in-person exam 4-6 weeks from dispense of glasses 
a. Standard binocular vision assessment for primary and secondary measurements  
7. Last assessment: 3 month phone call after dispense of glasses for last concussion survey   
 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
 
The main goal for this study is to determine the effectiveness of anti-fatigue (low additional prescription at near) in 
treating post-concussion patients for their visual symptoms. The main outcome measurement will be the 
convergence insufficiency symptom survey (CISS) pre-intervention and post-intervention of the anti-fatigue lenses. 
This will be compared to the CISS results of single vision glasses (rule out placebo effects) 
Other secondary outcome measurement will be objective measurements of vergence ranges and accommodation 
magnitude and flexibility, reduction of symptoms with single vision glasses alone for low refractive error 
individuals and the effects of anti-reflective coating. 
 
2.2 
BACKGROUND  
 
The CDC estimated that over half of the traumatic brain injury (TBI) emergency room visits were for patients 14 
years and younger in 20101. The actual incidence may be even higher due to unreported TBIs. Mild TBIs or 
concussions are the most common form of TBIs. There has been a recent increase in interest to understanding the 
effects of concussions on young patients. Children who sustain concussions tend to have worse and prolonged 
symptoms compared to adults2. These chronic symptoms commonly affect their cognitive ability, and mental and 
physical health.  
A number of studies have set out to determine the associated symptoms and the prevalence and duration of those 
symptoms. One study measured 73% of 247 concussed children 5-18 years old were still symptomatic 4 weeks 
post-concussion and 61% reported a decline in grades3.  Many studies4-5 agree that one of most common 
symptoms is visual complaints such as blurred vision and light sensitivity. There have been many studies 
documenting reduced accommodation and convergence in post-concussion patients5-6. Gallaway5 measured 47% 
and 42% of concussion patients had convergence insufficiency and accommodative insufficiency, respectively.  The 
slow resolution of these visual disorders may lead to disruptions in learning, many children requiring a median of 
12 days before returning to part time school3.  
Now that there is more knowledge of the repercussions from concussion, it is imperative that we continue to learn 
how to effectively treat and manage these disorders since the number of concussions is predicted to increase over 
the years. As of now, there is no standard of care or published effective treatment for binocular and 
accommodative issues for patients after a concussion. More standardized and objective concussion assessment 
and post-concussion treatment are needed in research.    
 
2.3 
RISK/BENEFIT ASSESSMENT   
 

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2.3.1 KNOWN POTENTIAL RISKS  
 
None. This study minimizes risk to the participant by using non-invasive procedures 
already being done as part of standard clinical eye care practice. Visual acuity, stereoacuity, 
ocular alignment, and other visual efficiency testing are done as part of standard practice. 
Unmasked investigators will be available to address these risks, allowing discontinuation of study 
treatment to pursue other interventions if needed. It is the investigator’s opinion that the 
protocol’s level of risk falls under DHHS46.404, which is research not involving greater than 
minimal risk. Although no adverse events are anticipated as a result of this treatment, all adverse 
events will be reported.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
It is possible that some of the patients might find resolution of symptoms depending on 
the treatment arm. The results of this research may change or help guide the treatment of 
concussion patients by providing evidence-based treatment results. Given the extensive costs 
related to concussion management and the cost of progressive addition lenses compared to 
typical glasses prescribed for children, this prospective project will help doctors and families 
make decisions on prioritizing treatment options following concussion. 
 
3 
STUDY DESIGN  
 
3.1 
OVERALL DESIGN 
  
This is a multi-site clinical trial (Identifier: NCT03123822) including Boston Children’s 
Hospital, Salus University Pensylvania College of Optometry, Dr. Nathan Steinhafel’s private 
practice, Akron Children’s Hospital, and the University of Alabama at Birmingham (coordinating 
site). All sites have identical study designs: a prospective randomized group comparison 
observational study with a masked examiner to treatment arm.  
 
3.2 
END OF STUDY DEFINITION 
 

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A participant is considered to have completed the study if he or she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of 
Activities (SoA), Section 1.3. 
 
The study is considered finished when the study has enrolled 90 participants total or if 
enrollment is too difficult or with too many adverse effects, then study may be terminated at 
the discretion of the principal investigator.   
 
4 
STUDY POPULATION 
 
4.1 
INCLUSION CRITERIA 
 
• 9-17 years of age 
• Sustained a concussion  ≥ 6 weeks ≤ 16 weeks from date of ophthalmic exam 
o 
Criteria for concussion: clinically diagnosed by physician  
• Best corrected visual acuity: 20/30 in both eyes at near; 20/25 in each eye at distance  
• Minimum Stereopsis: 500” global  
• CISS score ≥ 16 
• Refractive error at least   0.50D sphere or cylinder  
• Ability to clear ≥ 0.50 cycles per minute in monocular accommodative flipper of and binocular 
accommodative flipper  
 
4.2 
EXCLUSION CRITERIA 
 
• Diplopia from nerve palsies 
• Retinal pathology 
• Significant co-morbid neurodevelopmental disorder (e.g. autism spectrum disorder, brain 
injury, documented neurogenetic disorder; known brain malformation) 
• Intellectual/developmental delay 
• Prior diagnosis of ADHD that is not adequately controlled with medication 
• Previous treatment of any amount of bifocal lenses and base in prism since concussion 
o Vision therapy ≥ 6 weeks since concussion 
 
4.3 
SCREEN FAILURES 

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If a participant is later excluded from the study, they would be notified.  
 
4.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Recruitment will be directly from the eye clinics of Boston Children’s Hospital and the University of 
Alabama School of Optometry. Both clinics already have an established concussion clinic. We will 
provide patients with a $5 gift card if they complete the study, although this may be site dependent 
depending on funding.  
 
 
5 
STUDY INTERVENTION 
 
5.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
5.1.1 STUDY INTERVENTION DESCRIPTION 
 
Different types of glasses lenses that are already commercially available and have been commonly used 
to treat concussion patients through anecdotal experience.  
 
5.1.2 DOSING AND ADMINISTRATION 
 
Dosing is the same throughout treatment arms. Participants are expected to wear the glasses regardless 
of treatment arm every day. This would be self-administrated.  
 
 
5.2 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION 
 
Randomization is done as participants are recruited using an excel formula.  
 
5.3 
STUDY INTERVENTION COMPLIANCE 
 
The study will be completed by a new resident each year but the PI will have direct oversight of the 
resident to ensure that the protocol is adhered to. Compliance of the device will be self-reported by the 
participant.  
 
5.4 
CONCOMITANT THERAPY 
 
No concomitant therapy should take place during the study.  
 
 
6 
STUDY INTERVENTION DISCONTINUATION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL 

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6.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
If the adverse effects are significant, individual participants will be asked to terminate the study. 
Otherwise, the study may be terminated early due to difficulty in enrollment, per discretion of the PI.  
 
6.2 
SUBJECT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a subject from the study for the following reasons: 
 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
subject 
Subjects who sign the informed consent form and are randomized but do not receive the study 
intervention may be replaced.  Subjects who sign the informed consent form, and are randomized and 
receive the study intervention, and subsequently withdraw, or are withdrawn or discontinued from the 
study, will not be replaced. 
6.3 
LOST TO FOLLOW-UP 
A subject will be considered lost to follow-up if he or she fails to return for 2 scheduled visits and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a subject fails to be available for a required study visit: 
• 
The site will attempt to contact the subject and reschedule the missed visit and counsel the 
subject on the importance of maintaining the assigned visit schedule and ascertain if the subject 
wishes to and/or should continue in the study. 
• 
Before a subject is deemed lost to follow-up, the investigator or designee will make every effort 
to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a certified 
letter to the subject’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the subject’s medical record or study file.  
• 
Should the subject continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
 
7 
STUDY ASSESSMENTS AND PROCEDURES 
 
7.1 
STUDY ASSESSMENTS  
 
Study assessments will be done periodically.  
 
7.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
   

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7.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
7.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) is considered “serious” if, in the view of either the investigator or sponsor, it 
results in any of the following outcomes: 
 
• 
Death 
• 
A life-threatening adverse event (of note, the term “life-threatening” refers to an event in which 
the subject was at risk of death at the time of the event, rather than to an event which 
hypothetically might have caused death if it were more severe) 
• 
inpatient hospitalization or prolongation of existing hospitalization 
• 
a persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• 
or a congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 
7.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
7.2.3.1 SEVERITY OF EVENT 
For adverse events (AEs), the following guidelines will be used to describe severity:  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the subject’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a subject’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of 
note, the term “severe” does not necessarily equate to “serious.” 
 
7.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the subject based on temporal relationship and his/her clinical judgment. The 
degree of certainty about causality will be graded using the categories below. In a clinical trial, the study 
product must always be suspect.  
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 

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intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
7.2.3.3 EXPECTEDNESS  
The Principal Investigator will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
7.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study subject presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the study subject’s condition deteriorates at any time 
during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The Study Coordinator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the Study Coordinator will inquire about the occurrence of 
AE/SAEs since the last visit.  Events will be followed for outcome information until resolution or 
stabilization. 
 
7.2.5 ADVERSE AND SERIOUS ADVERSE EVENT REPORTING  
All serious adverse events must be reported to the IRB according to regulatory requirements. The 
Principal Investigator will immediately report to the sponsor any serious adverse event, whether or not 
considered study intervention related, including those listed in the protocol or package insert and must 
include an assessment of whether there is a reasonable possibility that the study intervention caused 
the event. Study endpoints that are serious adverse events (e.g., all-cause mortality) must be reported 
in accordance with the protocol unless there is evidence suggesting a causal relationship between the 
study intervention and the event (e.g., death from anaphylaxis). In that case, the investigator must 
immediately report the event to the sponsor. 
 

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All serious adverse events (SAEs) will be followed until satisfactory resolution or until the Principal 
Investigator deems the event to be chronic or the subject is stable. Other supporting documentation of 
the event may be requested and should be provided as soon as possible. 
 
7.3 
UNANTICIPATED PROBLEMS 
 
7.3.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
subjects or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
subject population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
7.3.2  UNANTICIPATED PROBLEM REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB). The UP report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB within 10 working days of 
the investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB within 10 working days of the investigator becoming 
aware of the problem.  
 
 
8 
STATISTICAL CONSIDERATIONS  
 
8.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Efficacy Endpoint(s):  

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The CISS score will be the efficacy endpoint. A CISS score of zero is considered complete resolution of 
the problem.  
 
• 
Secondary Efficacy Endpoint(s): 
 
TBD 
 
8.2 
SAMPLE SIZE DETERMINATION 
 
This was based on the funding we received from the lenses company.  
 
8.3 
STATISTICAL ANALYSES 
 
8.3.1 GENERAL APPROACH 
 
TBD 
 
8.3.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
TBD 
 
8.3.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
TBD 
 
8.3.4 SAFETY ANALYSES 
 
If the patient scores well below baseline, 10 points or more at the follow up appointment, then we may 
remove the patient from the study.  
 
8.3.5 BASELINE DESCRIPTIVE STATISTICS 
 
TBD 
 
 
9 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
9.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
9.1.1 INFORMED CONSENT PROCESS 
 
If eligible, the patient and their parent/guardian(s) will be informed of their eligibility immediately 
following their standard-of-care eye examination by study personnel. Details of the study will be 
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will be provided and reviewed by study personnel, and the patient and parent/guardian(s) will be given 
ample time to review the information, ask questions, and make a decision regarding participation. If the 
patient agrees to participate immediately, they will sign the appropriate consent/assent forms and then 
they can pick out frames the same day rather then come back for another time to pick out glasses. 
Participants can enroll up to 1 week after the enrollment visit if they provide their personal frames or 
choose from our selection. The families will be then asked to send the signed consent forms back to the 
investigator by email or regular mail. If the patient does not agree to participate there will be no 
consequence to them.  
 
9.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO SUBJECTS 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
subject and written documentation of informed consent is required prior to conducting study screening 
procedures. A separate screening consent form will not be used. 
 
9.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the subject will be asked to read and review the document. The 
investigator will explain the research study to the subject and answer any questions that may arise. A 
verbal explanation will be provided in terms suited to the subject’s comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research subjects.  Subjects will have 
the opportunity to carefully review the written consent form and ask questions prior to signing. The 
subjects should have the opportunity to discuss the study with their family or surrogates or think about 
it prior to agreeing to participate. The subject will sign the informed consent document prior to any 
procedures being done specifically for the study. Subjects must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of the 
informed consent document will be given to the subjects for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the form 
signed, before the subject undergoes any study-specific procedures. The rights and welfare of the 
subjects will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
9.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to regulatory authorities.  If the study is prematurely 
terminated or suspended, the Principal Investigator (PI) will promptly inform study subjects and the 
Institutional Review Board (IRB), will provide the reason(s) for the termination or suspension.  Study 
subjects will be contacted, as applicable, and be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
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• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the IRB. 
 
9.1.3 CONFIDENTIALITY AND PRIVACY  
Subject confidentiality and privacy is strictly held in trust by the participating investigators and their 
staff. Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the Principal Investigator.  
 
All research activities will be conducted in as private a setting as possible. 
 
Representatives of the Institutional Review Board (IRB) may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the subjects in this study. The clinical study site will permit access to 
such records. 
 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB and/or Institutional policies. 
 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, will be 
stored at the UAB Department of Otolaryngology research office. This will not include the subject’s 
contact or identifying information. Rather, individual subjects and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used by 
research staff will be secured and password protected.  
 
9.1.4 QUALITY ASSURANCE AND QUALITY CONTROL 
The site will perform internal quality management of study conduct, data collection, documentation and 
completion.  Quality control (QC) procedures will be completed by the Data Manager during data entry 
into the appropriate CRF. Any missing data or data anomalies will be communicated to the Study 
Coordinator for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated are collected, documented (recorded), and reported in compliance 
with the protocol, International Conference on Harmonisation Good Clinical Practice (ICH GCP), and 
applicable regulatory requirements.  
 
The site will provide direct access to all trial related sites, source data/documents, and reports for the 
purpose of monitoring and inspection by local and regulatory authorities. 
 
9.1.5 DATA HANDLING AND RECORD KEEPING  
 
9.1.5.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  

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Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
Principal Investigator. The Principal Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hard copies of source document worksheets will be used for recording data for each subject enrolled in 
the study.  Data recorded in the case report form (CRF) derived from source documents should be 
consistent with the data recorded on the source documents.  
 
9.1.5.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 3 years after the completion of the study. These 
documents should be retained for a longer period, however, if required by local regulations.  
 
9.1.6 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the subject, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the Principal Investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation.  Protocol deviations must 
be sent to the reviewing Institutional Review Board (IRB) per their policies. The Principal Investigator is 
responsible for knowing and adhering to the reviewing IRB requirements.  
 
9.1.7 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.   
 
 
 

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9.2 
ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DHHS 
Department of Health and Human Services 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IRB 
Institutional Review Board 
LSMEANS 
Least-squares Means 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
TBD 
To be determined  
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10 REFERENCES  
 
 
1. 
Goreth MB. Pediatric Mild Traumatic Brain Injury and Population Health: An Introduction for 
Nursing Care Providers. Crit Care Nurs Clin North Am. 2017;29(2):157-165. 
2. 
Zemek RL, Farion KJ, Sampson M, McGahern C. Prognosticators of persistent symptoms 
following pediatric concussion: a systematic review. JAMA Pediatr. 2013;167(3):259-265. 
3. 
Clark JF, Colosimo A, Ellis JK, et al. Vision training methods for sports concussion mitigation and 
management. J Vis Exp. 2015(99):e52648.