Efficacy of Glaucoma Drop Aids in Medication Compliance in the Patient Population at Boston Medical Center
Phase: NA
Conditions: Glaucoma
Sponsor: Boston Medical Center

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Glaucoma Drop Aid Study 
 
ClinicalTrials.gov number: NCT02867995 
Protocol Version Number: 1.5 
Protocol Version Date: 16 November 2017  
Funding Mechanism:  Boston Medical Center 
Principal Investigator: Manishi Desai, MD 
 
Phone: (617) 414-4071 
 
E-mail: Manishi.Desai@bmc.org 
 
CONFIDENTIAL 
 
This document is confidential and the property of Boston Medical Center. No part of it may be 
transmitted, reproduced, published, or used by other persons without prior written authorization 
from the study sponsor. 
 
 

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TABLE OF CONTENTS 
1 List of Abbreviations .................................................................................................................4 
2 Protocol Summary .....................................................................................................................4 
3 Background/Rationale & Purpose..............................................................................................5 
3.1 
Background Information .............................................................................................................. 5 
3.2 
Rationale and Purpose .................................................................................................................. 5 
4 Objectives ..................................................................................................................................6 
4.1 
Study Objectives .......................................................................................................................... 6 
4.2 
Study Outcome Measures ............................................................................................................ 6 
 
Primary Outcome Measures ...............................................................................6 
 
Secondary Outcome Measures ...........................................................................7 
5 Study Design ..............................................................................................................................7 
6 Potential Risks and Benefits ......................................................................................................7 
6.1 
Risks ............................................................................................................................................. 7 
6.2 
Unknown Risks ............................................................................................................................ 7 
6.3 
Potential Benefits ......................................................................................................................... 8 
6.4 
Analysis of Risks in Relation to Benefits .................................................................................... 8 
7 Study Subject Selection .............................................................................................................8 
7.1 
Subject Inclusion Criteria............................................................................................................. 8 
7.2 
Subject Exclusion Criteria ........................................................................................................... 8 
8 Study Intervention ......................................................................................................................8 
9 Study Procedures .......................................................................................................................9 
9.1 
Screening and Consent ................................................................................................................. 9 
9.2 
Day of Enrollment and Randomization...................................................................................... 10 
9.3 
Follow-Up Study Visits ............................................................................................................. 10 
 
3 Week Phone Call: .........................................................................................10 
 
Final Study Visit: At least 6 Weeks after Enrollment (SOC Clinic Visit).......10 
9.4 
Early Termination Visit ............................................................................................................. 10 
9.5 
Non-Study Visits (Unscheduled Visits) ..................................................................................... 11 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ...........................................11 
10.1 
Definitions .................................................................................................................................. 11 
10.2 
Safety Review ............................................................................................................................ 12 
10.3 
Reporting Plans .......................................................................................................................... 12 
10.4 
Stopping Rules ........................................................................................................................... 12 
11 Data Handling and Record Keeping ........................................................................................13 
11.1 
Confidentiality ........................................................................................................................... 13 
11.2 
Source Documents ..................................................................................................................... 13 
11.3 
Case Report Forms ..................................................................................................................... 13 
11.4 
Study Records Retention ............................................................................................................ 14 
12 Statistical Plan ..........................................................................................................................14 
12.1 
Study Hypotheses ....................................................................................................................... 14 
12.2 
Sample Size Determination ........................................................................................................ 15 
12.3 
Statistical Methods ..................................................................................................................... 16 
13 Ethics/Protection of Human Subjects ......................................................................................16 
14 Literature References ...............................................................................................................17 
15 Appendix ..................................................................................................................................18 

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15.1 
Schedule of Events: Source documents include medical records, satisfaction surveys, and all 
other information necessary to reconstruct and evaluate the clinical trial. See table 1 below for schedule of 
events. 
18 
15.2 
Case Report Forms (CRF).......................................................................................................... 19 
 Eligibility Assessment Form ............................................................................19 
 Documentation of Informed Consent...............................................................20 
 Home Study Diary ...........................................................................................21 
 Satisfaction Survey ..........................................................................................22 
15.3 
Drop Aid Label and Instructions ................................................................................................ 23 
 Drop Aid Label ................................................................................................23 
 Simply Touch Eye Drop Applicator Instructions ............................................24 
 Fabrication Autodrop Eye Drop Guide ............................................................25 
 Owen Mumford OP 6100 Autosqueeze ...........................................................26 
15.4 
AE, SAE, and UP Tracking and Reports ................................................................................... 27 
 Internal AE, SAE and UP Report Tracking Log (Sample) ..............................27 
 SAE and UP Report Form (Sample) ................................................................28 
 
 

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1 
List of Abbreviations 
 
Abbreviation 
Abbreviation definition 
AE’s 
Adverse events 
BMC 
Boston Medical Center 
BUMC 
Boston University Medical Campus 
cc 
Cubic centimeters 
FDA 
Food and Drug Administration 
ID 
Identification 
IOP 
Intraocular Pressure 
IRB 
Institutional Review Board 
mL 
Milliliters 
SAEs 
Serious adverse events 
SOC 
Standard of care 
UP 
Unanticipated problem 
VA 
Visual acuity 
 
2 
Protocol Summary 
Title: 
Glaucoma Drop Aid Study 
Population: 
Male and Female patients of Boston University Eye Associates, 18 
or older, having been receiving the same topical medication for 
treatment of glaucoma for a minimum of two months 
Intervention: 
Control: 
 
No Glaucoma Drop Aid Device 
Drop Aid Devices: 
 
Simply Touch Eye Drop Applicator 
 
Fabrication Autodrop Eye Drop Guide 
 
Owen Mumford OP 6100 Autosqueeze  
Objectives: 
To determine the efficacy of drop aid devices for improving 
medication compliance, visual function, and decreasing medication 
waste for patients at BMC 
Design/Methodology: 
Arm A: No intervention- Control 
Arm B: Active Comparator- Eye Drop Aids 
 
Participants will be randomly assigned into one of the study arms. If 
placed into Arm A, no drop aid device will be assigned.  If placed 
into Arm B, participants will be assigned one of the three drop aid 
devices (Simply Touch Eye Drop Applicator, Fabrication Autodrop 
Eye Drop Guide, or the Owen Mumford OP 6100 Autosqueeze).  
Total Study Duration: 
Approximately 1 year 
Subject Participation 
Duration: 
Subject participation length is variable based on appointment wait 
times and availability. The minimum duration of this study is 6 
weeks.  
 
 
 
 
 
 

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3 
Background/Rationale & Purpose 
 
3.1 
Background Information 
 
Glaucoma is a disease characterized by an increased intraocular pressure, resulting in damage to optic 
nerve.5 This disease can be diagnosed by measuring visual field loss, identifying other changes in the 
physical structures of the eye and by measuring IOP. If untreated, glaucoma can result in preventable 
vision loss.5 
 
Glaucoma is commonly treated with prescription eye drops.2,4 It is critical that patients receive the correct 
dose and frequency of eye drop medication as prescribed.2,4,5 This will prevent disease advancement and 
decrease the chances of vision loss.5 However, patient compliance with medication limits symptom 
improvement due to deliberate misuse, financial concerns, or unintentional issues in drug delivery.3 Some 
patients have difficulty putting in the correct amount of eye drops themselves.4 Common problems are 
from a patient missing their eye, delivering too much medication, or they are unable to squeeze the bottle 
properly. This can create further problems with pharmacy refills, as well as financially from buying an 
increased number of prescriptions.3 In order to ensure patients are receiving the correct amount of drops 
with each use, drop aids are available at local pharmacies for purchase.4 These are not commonly 
recommended because they can be costly and their usefulness has not yet been proven.2,4 Although if a 
drop aid proves to be effective, they may result in a decrease of cost for the patient in the long term by 
allowing a decrease in premature completion of the bottle.3, 4   
 
This study aims to determine the efficacy of glaucoma drop aids delivery of ophthalmic medications by 
improving medication compliance, visual function, and decreasing medication waste in the patient 
population at BMC.  
 
This study will be conducted in compliance with the protocol, applicable regulatory requirements, and 
BMC/BU Medical Campus Human Research Protection policies and procedures. 
 
3.2 
Rationale and Purpose  
 
The ophthalmology department at Boston Medical Center sees on average 275 glaucoma patients weekly, 
80 percent of which are placed on glaucoma medications. It is critical for these patients to receive the 
correct dose and frequency of their eye drops, in order to prevent disease advancement and decrease the 
chances of vision loss.4 However, a majority of patients are unable to properly deliver the eye drops into 
their eyes due to poor vision or difficulty squeezing drop bottles. 3,4 Furthermore, when patients are able 
to instill drops into their eyes, they often deliver more than a necessary amount, leading to premature 
completion of the bottle. This is an issue in the United States, as most glaucoma patients are on 2 to 3 
different medication drops and Medicare Part D sponsors permit refills at only 70% of predicated days of 
use, accounting for about half of glaucoma patient population.1 Self-reported studies also showed that 
approximately 25% of patients reported problems with early exhaustion of eye drop bottles.1 The average 
size of a glaucoma medication bottle is around 10 cc and these medications, when used 2 to 3 times daily, 
are expected to last patients an entire month.  When used in excess or reduction, problems may occur with 
pharmacy refills, an addition to financial burdens from buying an increased number of prescription 
refills.1 In the absence of good medication compliance and response, patients often have to undergo costly 
surgical procedures that can place them at an increased risk of infection and loss of vision, while still 
requiring postoperative management with ophthalmic drops, in addition to being closely monitored by 
eye care providers.1  
 

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In order to ensure patients are receiving the correct amount of drops with each use, there are many drop 
aid assistive devices available for purchase on the market; however, these drop aids are not routinely 
offered to our patients because of their unproven cost benefit ratio, and the poorly studied efficacy of the 
devices.4 Although, if a drop aid proves to be effective, the cost of the drop aid devices would more than 
pay themselves through the improvement in medication compliance and visual function of our patients. 
The “Glaucoma Drop Aid Study” aims to determine if using drop aids during the administration of eye 
drop medication leads to better results for patients with glaucoma at Boston Medical Center. The 
implications of this study may show an improved delivery system of ophthalmic medications thus 
improving medication compliance, visual function, and even decreasing medication waste. 
 
4 
Objectives 
 
4.1 
Study Objectives 
 
The primary objective of this study is to compare efficiency of various drop aids for glaucoma 
medications objectively via changes in intraocular pressure. The different drop aids that are utilized are 
the Simply Touch Eye Drop Applicator, the Fabrication Autodrop Eye Drop Guide, and the Owen 
Mumford OP 6100 Autosqueeze. The central hypothesis is that the use of a drop aid device increases 
efficiency of glaucoma medication when comparing changes in intraocular pressure. 
 
A secondary objective of this study is to evaluate how often a patient missed their eye when instilling 
drops with various drop aids in order to assess whether drop aids can decrease medication waste, increase 
medication compliance, and improve visual function. Additionally, the study will analyze how satisfied 
the patient is with their drop aid and the likelihood they would continue to use one outside of the study. 
These satisfaction means will be evaluated with a patient satisfaction survey approximately 3 weeks and 6 
weeks after enrollment.  
 
4.2 
Study Outcome Measures 
 
The efficiency of various drop aids will be measured through the subject’s glaucoma progression at the 
end of the study. On the day of enrollment, the subject’s IOP and visual acuity will be measured as part of 
their standard of care exam. This information is recorded as the baseline exam, and will be compared to 
measure the patient’s glaucoma progression at the end of the study. Subjects will be required to record the 
date on which they began each of their glaucoma eye drop bottles, and the date each bottle was finished in 
a study diary provided by the research team. Subject’s satisfaction will be measured through a brief 
satisfaction survey approximately 3 weeks after their enrollment.  After at least 6 weeks of study 
participation, subject will be followed up with their regularly scheduled glaucoma provider where they 
will fill out a second brief satisfaction survey. The study diary will be collected and a routine eye exam 
will be conducted, with their IOP checked as part of a standard of care clinic visit.  
 
All surveys were created by a member of the research team. The satisfaction survey includes five 
questions to assess the precision of the drop aid device, overall patient satisfaction, and willingness to use 
the device long term. The questions are multiple choice questions in which the patient circles the answer 
that best reflects their response.  
 
Reference Section 12.0 for further statistical analysis explanations. 
 
 Primary Outcome Measures 
 

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The objective of this study is to compare efficiency of various drop aids for glaucoma medications 
objectively via changes in intraocular pressure.  
 
 Secondary Outcome Measures 
 
The following secondary outcomes will also be measured: 
1. Number of times a patient missed their eye when instilling eye drops 
2. Patient satisfaction responses with treatment arms 
3. Intention to use a drop aid long term 
 
5 
Study Design 
 
This interventional clinical trial is a prospective, single center, randomized controlled study. Patients 
being treated for their glaucoma at BMC's Yawkey Eye Clinic will be selected. Patients will be randomly 
placed, without manipulations by the principle investigator or any member of the research team, on one of 
the drop aid devices (including Fabrication Autodrop Eye Drop Guide, Simply Touch Eye Drop 
Applicator, Owen Mumford OP 6100 Autosqueeze), in addition to a no drop aid control, for a total of 4 
groups. 
 
Subjects have an equal chance of being randomized to one of the following study arms: 
 
Arm A: No intervention – Control 
 
Arm B: Active Comparator- Eye Drop Aids Including: 
o Simply Touch Eye Drop Applicator 
o Fabrication Autodrop Eye Drop Guide 
o Owen Mumford OP 6100 Autosqueeze 
 
The primary endpoint is the comparison of baseline IOP measurement and follow-up IOP measurement. 
This comparison will determine the efficacy of using a drop aid. The secondary endpoints include the 
precision of the drop aid, patient satisfaction, and their likelihood to use a drop aid outside of the study. 
Data collection for assessment of study objectives will be obtained via standard of care clinic visits and 
completion of study diary and satisfaction survey by the patient with assistance of research team, if 
needed. 
 
See the Appendix section 15.1 for a schematic of the study design and section 15.3 for drop aid labels and 
instructions.  
 
6 
Potential Risks and Benefits 
 
6.1 
Risks 
 
Risks and possible discomforts involved with study participation are associated with eye dropper use and 
the possibility of a breach of confidentiality. The use of the assigned drop aid does not pose any 
additional risk to subjects from only using an eye drop bottle for administration. Both methods of eye 
drop administration pose the same risk of corneal abrasion or infection from poking the eye with the 
device/bottle, or using a dirty device/bottle. Subjects will be advised by the investigator on how to 
decrease these risks when administering drops with the assigned device.  
 
There is the unlikely possibility of breach of confidentiality. Confidentiality will be protected as stated in 
Section 11.1 of this protocol.  
6.2 
Unknown Risks 

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There may be unknown risks or discomfors involved. Study staff will update all subjects in a timeley 
manner with any new information that may affect their health, welfare, or decision to participate in this 
study.  
 
6.3 
Potential Benefits 
 
Study participants may benefit from participation by improved eye drop compliance, decrease in 
medication refill requirements, receiving a drop aid at no cost, and an overall increased satisfaction with 
eye drop medications. It is also possible that subjects may not receive any direct benefit from 
participation, but they will be helping investigators learn about the benefits of drop aids as well as better 
understand the efficacy of its usage for patients at BMC. 
 
6.4 
Analysis of Risks in Relation to Benefits 
 
The project allows for potential improvement in patients’ medication compliance. These drop aids are 
designed to help deliver only the necessary amount of medication and target the eye to allow for easier 
delivery of medications. The drop aids involved in this study are targeted toward improving patient 
experience when using glaucoma medications. This may reduce patient frustration and increase adherence 
to medication allowing for better glaucoma treatment outcomes. The risks of this study include a minimal 
risk of loss of confidentially. The risk is minimal in comparison to the potential benefits of: improved 
medication compliance, monetary benefits of decreased number of refills, increased patient satisfaction 
with eye drop medications, and community benefit of understanding the effectiveness of drop aids.  
 
7 
Study Subject Selection 
 
7.1 
Subject Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
Age 18 years or older 
 
Currently on the same topical medication for treatment of glaucoma for a minimum of two 
months 
 
Patient of Boston University Eye Associates 
 
Agrees to use the drop aid with each delivery, return to the clinic after approximately 6 weeks 
of using the drop aid, document completion of medication drops, and fill out survey at the 
end of the 6 weeks 
 
7.2 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
Changes glaucoma medication within the past two month or recent glaucoma surgery 
 
Not a patient of the Boston University Eye Associates 
 
8 
Study Intervention 
 
Arm A: No intervention – Control 
Arm B: Active Comparator – Eye Drop Aids Including: 
 
Simply Touch Eye Drop Applicator 
 
Fabrication Autodrop Eye Drop Guide 

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 
Owen Mumford OP 6100 Autosqueeze 
 
Drop Aid devices were funded by a Boston Medical Center grant award. Devices were purchased by the 
grant award at no cost to the patients. Drop aid devices will be ordered online using the funds provided by 
the grant award. Upon arrival to Boston Medical Center, drop aid devices will be stored in locked 
cabinets that only the research team can access. Each drop aid will have a study-specific label indicating it 
is an investigational device provided by BMC. Administration of the drop aid devices will occur after 
consenting procedures and randomization to a treatment or control arm. Patients will be instructed by a 
member of the research team how to use the device. Patients will be expected to use the device each time 
they administer their eye drops as directed by their provider.   
 
Compliance to drop aid device will be assessed via patient satisfaction surveys. Patient satisfaction 
surveys ask the participant to confirm the usage of drop aid device after administration of device at the 3 
week phone call and 6 week follow-up.  
 
Reference Appendix sections 15.3 for drop aid labels and instructions.  
 
9 
Study Procedures 
 
See the Appendix section 15.1 for the schedule of events.  
 
The following study procedures will be performed for study-specific purposes: 
 
Review of inclusion/exclusion criteria for eligibility 
 
Informed consent 
 
Study specific medical, ophthalmic, and family history 
 
Randomization: eligible subjects will be randomized into either Arm A or Arm B, and assigned 
no device or one of the three drop aid devices 
 
Completion of phone call satisfaction survey approximately three weeks after enrollment 
 
Completion of satisfaction survey at follow-up visit approximately six weeks after enrollment 
 
Collection of information regarding length of medication usage 
 
Collection of information regarding any AEs, SAEs, or UPs. 
 
The following procedures will be performed as SOC: 
 
Ophthalmic exam prior to enrollment 
 
Ophthalmic exam six weeks after enrollment 
 
9.1 
Screening and Consent 
 
Glaucoma ophthalmology patients who are thought to be eligible for the study based on the eligibility 
criteria and review of their medical record by the investigator and/or designated study team member will 
be approached about study participation. The patient’s provider (who could be an investigator) will 
introduce the study to the patient. The provider will alert the investigator (if they are not already an 
investigator) and/or the designated study team member to assist with enrollment. The following will then 
be completed by the investigator and/or the designated study team member: 
 
Review of study inclusion/exclusion criteria 
 
The consent form will be reviewed with the patient and all study related questions will be 
answered in a private exam room or consult room. 
o Both the patient and the investigator or the designated study team member conducting the 
consent form will sign 

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o The patient will be sent home with a copy of the fully executed consent form 
o The patient will also be given the contact information of the principal investigator, 
clinical research coordinator, and 24-hour emergency number as listed below: 
 
Manishi Desai, MD 
Principal Investigator 
Manishi.Desai@bmc.org 
(617) 414-4071 
 
Marissa Fiorello 
Clinical Research Coordinator 
Marissa.Fiorello@bmc.org 
(617) 414-8848 
 
BMC Department of Ophthalmology 
Emergency after Hours 
(617) 638-8000, dial 0 for operator, and ask for on-call ophthalmologist 
 
o Study-specific review of medical record and demographics 
 
9.2 
Day of Enrollment and Randomization 
 
Subject’s IOP and VA will be measured as part of SOC exam 
 
Dispense study diary 
o Patients will be requested to record the number of days taken to complete the glaucoma 
medication bottle 
 
Randomization: After enrollment, subjects will be randomly assigned to Arm A or Arm B, and 
assigned no device or one of the three drop aid devices 
 
Subject will be instructed on how to use the drop aid by a member of the research team 
 
Subject will be requested to administer their drops with the drop aid, or no drop aid if randomized 
into the control group, with every use 
 
A member of the research team will confirm the subject’s phone number and schedule a time for 
the 3 week phone call  
 
9.3 
Follow-Up Study Visits 
 
 3 Week Phone Call:  
 
Subject will complete satisfaction survey for all drop aid treatment or control groups over the 
phone 
 
Confirm next SOC clinical visit 
 
 Final Study Visit: At least 6 Weeks after Enrollment (SOC Clinic Visit) 
 
Subject will complete a satisfaction survey in person 
 
Subject’s study diary will be collected 
 
Routine eye exam will be conducted 
o IOP and VA will be checked as part of SOC clinic visit 
 
Study participation is complete  
  
9.4 
Early Termination Visit 

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The subject can be terminated early from the study if there is a change in eye medication as determined 
by their SOC provider. Subjects can also be withdrawn from the study if they demonstrate non-
compliance for study procedures.  
 
9.5 
Non-Study Visits (Unscheduled Visits) 
At non-study visits a standard office ophthalmology exam will be completed. 
 
Reference Appendix section 15.1 for schedule of events.  
 
Reference Appendix section 15.2 for complete CRF used for all study visits which include patient 
satisfaction survey and study diary.  
 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) 
 
10.1 Definitions 
 
The following definitions will be used in the assessment of safety: 
 
Adverse Event (AE) is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered related to 
the subject’s participation in the research. 
 
Serious Adverse Event (SAE) is any adverse event that  
(1) results in death; 
(2) is life-threatening; 
(3) results in inpatient hospitalization or prolongation of existing hospitalization; 
(4) results in a persistent or significant disability/incapacity; 
(5) results in a congenital anomaly/birth defect; or 
(6) based upon appropriate medical judgment, may jeopardize the subject's health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition 
(examples of such events include allergic bronchospasm requiring intensive treatment in the 
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).  
 
Life-threatening means that the event places the subject at immediate risk of death from the event as it 
occurred.  
 
Unanticipated Problem is defined as an event, experience or outcome that meets all three of the 
following criteria:  
 
is unexpected; AND 
 
is related or possibly related to participation 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.  
 
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 
 
Unexpected means the nature, severity, or frequency of the event is not consistent with either: 

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 
the known or foreseeable risk of adverse events associated with the procedures involved in the 
research that are described in (a) the protocol–related documents, such as the IRB-approved 
research protocol, any applicable investigator brochure, and the current IRB-approved informed 
consent document, and (b) other relevant sources of information, such as product labeling and 
package inserts; or 
 
the expected natural progression of any underlying disease, disorder, or condition of the subject(s) 
experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse 
event. 
 
10.2 Safety Review 
 
Both the risks listed in Section 6.1 and unknown risks will be monitored throughout this minimal risk 
study. The PI will have overall responsibility for the study. The PI will review all AEs, SAEs, and UPs. 
During the review, the PI will complete the form designated in Appendix 15.4.1 in which the AE will be 
graded and the relatedness will be determined. All SAEs and UPs will be promptly reported to the BUMC 
IRB as designated in Section 10.3. The SAE Report demonstrated in Appendix Section 15.4.2 will be 
completed for all SAEs and UPs.      
  
Dr. Manishi Desai is the PI and will be responsible for the study. Dr. Desai will be notified within 1 week 
of any events determined an AE or SAE and 2 days of any event determined a UP. Dr. Desai will review 
all AEs/SAEs within 2 weeks and all UPs within 5 days. After this review, any recommended changes 
will be made to the PI and the co-investigators in addition to the BUMC IRB as deemed necessary by the 
PI.   
  
Reference Appendix section 15.4 for all AE, SAE, and UP tracking and report examples.   
 
10.3 Reporting Plans 
 
The Principal Investigator at BMC/BU Medical Campus will report Unanticipated Problems, safety 
monitors’ reports, and Adverse Events to the BMC/BU Medical Center IRB in accordance with IRB 
policies: 
 
Unanticipated Problems occurring at BMC/BU Medical Campus involving a fatal or life-
threatening event will be reported to the IRB within 2 days of the investigator learning of the event. 
 
Unanticipated Problems occurring at BMC/BU Medical Campus not involving a fatal or life-
threatening event will be reported to the IRB within 7 days of the investigator learning of the event. 
 
Reports from safety monitors with recommended changes will be reported to the IRB within 7 days 
of the investigator receiving the report.  
 
Adverse Events (including Serious Adverse Events) will be reported in summary at the time of 
continuing review, along with a statement that the pattern of adverse events, in total, does not 
suggest that the research places subjects or others at a greater risk of harm than was previously 
known. 
 
Reports from safety monitors with no recommended changes will be reported to the IRB at the time 
of continuing review.  
 
10.4 Stopping Rules 
 
A subject will be withdrawn from the study for any of the following reasons but are not limited to:  
 Change to eye drop regimen as determined by their SOC provider 

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 Failure to comply with drop aid instructions 
 SAE or UP resulting from the administered study device 
 
The study will be stopped if the PI, Dr. Manishi Desai, determines that the number of AEs, SAE, and/or 
UPs exceed that of SOC ocular procedures.   
 
11 Data Handling and Record Keeping 
 
11.1 Confidentiality 
 
The clinical research staff in the Department of Ophthalmology at BMC has sole accessibility to view 
patient identifiers for eligibility review. After the patient is consented into the study, each patient will 
receive a unique study ID number to protect subject identity. Subject identifiers and study ID numbers 
will be linked in a secure, password-protected master database located in a departmental networked 
serves, housed behind BMC’s firewall. The master database will allow for subject re-identification, as 
necessary, for strict research-specific purposes. Only study personnel will have access to the master 
database. 
 
Any paper records related to this study will be stored in locked cabinets or in a locked office. Any 
data that is analyzed by an outside source will not contain any identifiers. In the event that any 
information is stored on external storage, the data will be encrypted. Patient information will not be 
used in any other way than described in this protocol.  
 
A description of this clinical trial will be available on http://clinicaltrials.gov, as required by U.S. 
Law. The website will not include information which can identify any of the subjects. At most, the 
website will include a summary of the results. The subject is able to search for the study at any time 
on the website by utilizing the ClinicalTrials.gov number shown on the first page of this protocol. 
 
11.2 Source Documents 
 
All source documents for this study will include the electronic medical record and the study-specific 
documents which includes the following:  
 
CRFs in Appendix section 15.2 
 
Patient Satisfaction Survey Appendix section 15.2.4 
 
AE, SAE, and UP tracking reports in Appendix section 15.4 
 
Data generated by the methods described in the protocol may be recorded in the subjects' medical records 
and/or study progress notes. Data may be transcribed legibly on CRFs supplied for each subject or 
directly inputted into an electronic system or any combination thereof. 
 
11.3 Case Report Forms 
 
The study case report form (CRF) will be the primary data collection instrument for the study. All data 
requested on the CRF will be recorded. All missing data will be explained. If a space on the CRF is left 
blank because the procedure was not done or the question was not asked, “N/D” will be written. If the 
item is not applicable to the individual case, “N/A” will be written. All entries will be printed legibly in 
black ink. If any entry error has been made, to correct such an error, a single straight line will be drawn 
through the incorrect entry and the correct data will be entered above it. All such changes will be initialed 

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and dated.  There will be no erasures or white-out on CRFs.  For clarification of illegible or uncertain 
entries, the clarification will be printed above the item, then initialed and dated.  
 
See the Appendix section 15.2 for the following CRFs: Eligibility Assessment Form, Documentation of 
Informed Consent, Home Study Diary, and the Satisfaction Survey. 
 
11.4 Study Records Retention 
 
In accordance with BMC policy, the study records will be retained for at least seven years after 
completion of the study. Additionally, as required by the BMC/ BUMC IRB, documentation of informed 
consent of subjects will be retained for at least three years after the study is closed. All of the required 
records may be preserved in hard copy, electronic, or other media form and must be accessible for 
inspection and copying by authorized individuals.  
 
12 Statistical Plan 
 
12.1 Study Hypotheses 
 
12.1.1. Primary Objective: Intraocular Pressure 
 
Formal hypothesis: Drop aids will be cost-effective in delivery of ophthalmic medications by improving 
baseline IOP measures to six week visit.  
 
Testable hypothesis: Patient baseline IOP measures will be a statistically significantly improvement in 
accordance to the usage of a drop aid device.   
 
Null hypothesis: The patients, who are assigned to a drop aid device baseline IOP measures will not have 
a statistically significant change with the usage of a drop aid device when compared to patients not 
assigned to a drop aid device.  
 
Alternate hypothesis: Patients not assigned to a drop aid device will result in larger significant change 
when compared to patients who are assigned to a drop aid device.  
 
 
 
 
H0: µ0  <  µd – δ 
 
 
 
 
HA: µ0  ≥  µd – δ 
 
Where µ0, is the true mean IOP change from baseline to the six week visit without the drop aid device, µd 
is the true mean IOP change from baseline to the six week visit with the drop aid device. 
 
12.1.2. Secondary Objective: Drops Missed 
 
Formal hypothesis: Drop aids will be effective in delivering the proper amount of drops, thereby reducing 
the number of missed drops for patients.  
 
Testable hypothesis: Differences in drops missed with drop aid device compared to without drop aid 
device will show efficacy in drop aid device.  
 
Null hypothesis: Patients assigned to a drop aid device will not result in less drops missed when compared 
to patients who are not assigned to a drop aid device.  
 

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Alternate hypothesis: Patients assigned to a drop aid device will result in minimal missed drops when 
compared to patients who are not assigned to a drop aid device.  
 
12.1.3. Secondary Objective: Patient Satisfaction 
 
Formal hypothesis: Drop aid devices will prove greater patient satisfaction than administrations without a 
drop aid device.  
 
Testable hypothesis: Mean patient satisfaction to those assigned to a drop aid device compared to mean 
patient satisfaction scores to those not assigned to a drop aid device.  
 
Null hypothesis: Patients assigned to a drop aid device will not show greater patient satisfaction than 
patients not assigned to a drop aid device.  
 
Alternate hypothesis: Patients assigned to a drop aid device will show greater patient satisfaction than 
patients not assigned to a drop aid device.  
H0: µs  <  µsd – δ 
 
 
 
 
HA: µs  ≥  µsd – δ 
 
Where µs, is the mean patient satisfaction without the drop aid device, µsd is the mean patient satisfaction 
with the drop aid device.  
 
12.1.4. Secondary Objective: Intention of Long term use  
 
Formal hypothesis: Patients assigned to a drop aid device will claim greater interest in long term use of 
the drop aid device, than declining long term use of the drop aid device. 
 
Testable hypothesis: Mean patients claiming interest in long term use of the drop aid device compared to 
mean patient declining interest in long term use of the drop aid device.  
 
Null hypothesis: Patients assigned to a drop aid device will not show greater mean interest in long term 
use of the drop aid device. 
 
Alternate hypothesis: Patients assigned to a drop aid device will show greater mean interest in long term 
use of the drop aid device.  
H0: µy  <  µn – δ 
 
 
 
 
HA: µy  ≥  µn – δ 
 
Where µy, is the mean patients who claimed interest in long term use of the device, µn is the mean patient 
who denied interest in long term use of the device.  
 
12.2 Sample Size Determination 
 
The sample size was determined by the maximum number of subjects which could be randomized given 
the budgetary constraints of the grant funding. It was determined that a total of ten patients per group was 
financially feasible, thus a total of 40 patients will be enrolled in this study in approximately 1 year. 
 
Enrolling the projected 40 subjects in 1 year is feasible, as the ophthalmology department sees 
approximately 275 glaucoma patients weekly. Due to the high volume of the glaucoma clinic, the study 
team should be able to easily recruit their target. Additionally, the study team is comprised of multiple 

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investigators and research assistants who have been delegated tasks on this protocol which can provide 
full-time recruitment coverage.    
 
12.3 Statistical Methods 
 
A variety of statistical analysis will be used to analyze the results. A paired t-test will be the primary 
method of analysis. Any significant differences measured will be between the pre and post intervention, 
with the patient serving as their own control. However, the analysis will not be limited to a paired t-test 
and will also likely include ANOVA, chi-squared, p-value, linear regression, among others.  Other 
outcomes such as length of time until completion of drops will also be measured and compared to no drop 
aid controls. Significant differences will be measured with similar statistical analysis as stated previously. 
Satisfaction of use will be measured with a survey and results will be averaged among those in the same 
cohort. Any significant differences will also be measured with similar statistical analysis stated 
previously. 
 
13 Ethics/Protection of Human Subjects 
 
This study is to be conducted according to applicable US federal regulations and institutional policies 
(which are based in federal regulations, guidance, and ICH Good Clinical Practice guidelines). 
 
This protocol and any amendments will be submitted to the Boston Medical Center and Boston University 
Medical Campus IRB, for formal approval of the study conduct. The decision of the IRB concerning the 
conduct of the study will be made in writing to the investigator.  
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. The consent 
form will be submitted with the protocol for review and approval by the IRB. The consent of a subject, 
using the IRB-approved consent form, must be obtained before that subject is submitted to any study 
procedure. Consent will be documented as required by the IRB.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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14 Literature References 
 
1. American Glaucoma Society. American Glaucoma Society. 
https://www.americanglaucomasociety.net/patients/position_statements/glaucoma_eye_drop_avail
ability. Published July 2009. Accessed October 25, 2017.  
2. Ghate, D., & Edelhauser, H. Barriers to glaucoma drug delivery. Journal of Glaucoma. 2008; 
17(2), 147-56. doi:10.1097/IJG.0b013e31814b990d 
3. Rivers, P. Compliance aids--do they work? Drugs & Aging. 1992; 2(2), 103-11. 
doi:10.2165/00002512199202020-00004 
4. Salyani, & Birt. Evaluation of an eye drop guide to aid self-administration by patients experienced 
with topical use of glaucoma medication. Canadian Journal of Ophthalmology/Journal Canadien 
D'ophtalmologie.2005;40(2), 170-174. doi:10.1016/S0008-4182(05)80028-6. 
5. Sommer, Alfred. Intraocular Pressure and Glaucoma. American Journal of Opthalmology, 1989; 
107 (2), 186-188.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15 Appendix 
 
15.1 Schedule of Events: Source documents include medical records, satisfaction surveys, and all other 
information necessary to reconstruct and evaluate the clinical trial. See table 1 below for schedule 
of events. 
 
Table 1: Schedule of Events. This table demonstrates the procedures to completed at each study visit. 
Procedures 
Screening and 
Consent 
Randomization 
3 Week 
Phone Call 
6 Week 
Follow-up 
Visit 
Informed consent 
X 
 
 
 
Study specific review of 
medical/ophthalmic history 
X 
 
 
 
Study specific review of 
demographics 
X 
 
 
 
Review of 
inclusion/exclusion criteria 
X 
X 
X 
X 
IOP and VA check 
X 
 
 
X 
Randomization 
 
X 
 
 
Dispense drop aid (if 
applicable) 
 
X 
 
 
Teach/emphasize drop aid 
usage and compliance (if 
applicable) 
 
X 
X 
 
Dispense study diary 
 
X 
 
 
Confirm contact information 
X 
X 
X 
 
Schedule/Confirm Follow-up 
Visits 
X 
X 
X 
 
Completion of satisfaction 
survey 
 
 
X 
X 
Collect study diary 
 
 
 
X 
Assessment of possible AEs 
and/or SAEs 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.2 Case Report Forms (CRF) 
 
 Eligibility Assessment Form 
 
Study Name: 
Glaucoma Drop Aids 
IRB Protocol #: 
H-34905 
Protocol Version # and/or Date: 
 
Principal Investigator: 
Manishi Desai, MD 
 
 
SUBJECT # _____________________ 
INCLUSION CRITERIA 
Must be "yes" 
Yes 
No 
Location of supporting 
source documentation 
Notes 
1. Age 18 years or greater 
 
 
 
 
2. Patient of Boston University 
Eye Associates 
 
 
 
 
3. Currently on the same 
topical ophthalmic medications 
for treatment of glaucoma for 
minimum of two months 
 
 
 
 
 
 
This subject is: 
 
      Eligible for participation               Ineligible for participation 
 
 
Signature: 
 
Date: 
 
Printed Name: 
 
 
 
 
 
 
 

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 Documentation of Informed Consent 
 
Participant: 
 
Version of consent used: 
 
Consent obtained by: 
 
Date of consent: 
 
 
Check all that apply (provide necessary details in the notes space below):  
 The study was explained and the consent form was reviewed with the participant. 
 All of the participant’s questions were answered and all the consent elements, such as 
purpose, procedures, and risks were reviewed.  
 The participant was given sufficient time to consider participation. 
 The participant agreed to participate in the study and personally signed and dated the 
consent form. 
 
  Verbal consent/assent was obtained (as approved by the IRB). 
  Obtained consent from Legally Authorized Representative (as approved by 
the IRB). 
 The consent form was signed and dated by the researcher. 
 The consent process was witnessed by an impartial witness (if applicable). 
 The participant was given a copy of the signed informed consent form. 
 The consent process was completed prior to the start of research procedures. 
 
Notes about the consent process (i.e. who was involved in consent process, what questions 
did the participant have, translator number, whether a teach-back process was used, etc.): 
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
_______________________________________________________________________ 
 
Signature or initials of person completing this form: ______________________ 
Date form completed: __________________ 
 
 
 
 
 
 
 
 
 
 

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 Home Study Diary 
 
Individual(s) completing this form:   □ Study Subject   □ Research team member: _____ (initials) 
Date of completion: ___________________ 
 
Study ID 
 
Medication Name: __________  
Start Date:_________________ 
 
End Date: _________________ 
 
Medication Name: __________  
Start Date:_________________ 
 
End Date: _________________ 
 
Medication Name: __________  
Start Date:_________________ 
 
End Date: _________________ 
 
Please complete this paper and bring it to your next eye appointment 
along with your drop aid and eye drops 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 Satisfaction Survey 
 
Study ID: ____________________ 
Name of study team member completing this form: ________________________ 
Date: _________________________ 
Study Visit: 
□ 3-week phone call 
□ Follow-up clinic visit 
1. Do you like the drop aid? 
a. 
Yes 
b. No 
c. 
I am not on a drop aid 
d. I did not use the drop aid 
2. Is it easier to instill drops with the help of the drop aid compared without the drop aid? 
a. 
Yes 
b. No 
c. 
I am not on a drop aid 
d. I did not use the drop aid 
3. How many times did you miss instilling drops with the help of drop aid? 
a. 
None 
b. 1 
c. 
2 
d. 3 or more 
e. 
I am not on a drop aid 
f. 
I did not use the drop aid 
4. How many times do you miss instilling drops just using your glaucoma drops? 
a. 
None  
b. 1 
c. 
2 
d. 3 or more 
5. Would you use the drop aid long term? 
a. 
Yes 
b. No  
c. 
I am not on a drop aid 
d. I did not use the drop aid 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.3 Drop Aid Label and Instructions 
 
 Drop Aid Label 
The label below was placed on each individual drop aid box in order to identify it as an 
investigational device provided by BMC.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 Simply Touch Eye Drop Applicator Instructions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 Fabrication Autodrop Eye Drop Guide 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 Owen Mumford OP 6100 Autosqueeze 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.4 AE, SAE, and UP Tracking and Reports 
 
 Internal AE, SAE and UP Report Tracking Log (Sample) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 SAE and UP Report Form (Sample) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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