Clinical trial NCT03246724
Conditions: Surgery Sedation
Keywords: Ocular surgery Intravenous sedation Oral sedation
Sponsor: Boston Medical Center
Start date: 2017-10-16; Completion date: 2019-11-30
Enrollment: 327 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate patient satisfaction after eye surgery when given a capsule compared to an intravenous (IV) dose of sedation (calming medication).

Each subject will be given a capsule and an IV in the hospital before their procedure starts, however they will not know which one is the sedation route. Each subject will have their planned surgical procedure as previously discussed with their doctor. After the procedure is completed, the doctors will complete satisfaction surveys. The subject will also complete a satisfaction survey during their regularly scheduled visit the day after surgery. Once the subject completes this survey, their study participation will be complete.

The hypothesis is that there will be no difference in patient satisfaction when given a capsule in comparison to IV sedation. If the results of the study support this hypothesis, a capsule could be used in place of IV sedation. By using a capsule for ocular procedures, both patients and the medical practice would benefit: patient would be able to eat before their procedure, patient costs would be decreased, hospital costs would be reduced, and some of these procedures would be given the option to move to a procedure room (freeing up operating room time for other departments).

Detailed description:
The primary objective of this study is to compare patient satisfaction of oral triazolam to IV midazolam when administered for ocular procedures. Midazolam is an FDA-approved intravenous medication commonly used as a sedative for ocular procedures conducted in the operating room. This study will compare the use of triazolam, an FDA-approved oral sedative for the same types of ocular procedures, a purpose which has not fully been investigated. The benzodiazepine triazolam was chosen as the oral medication due to its similarity to midazolam. The similarities between midazolam and triazolam include similar half-life, risks, and patient experience.The medication doses were chosen from current SOC use based on weight. The lower dose for both medications are used for patients with a BMI less than 35 and the higher dose is used for patients with a BMI greater than or equal to 35.

This is the first double-blind, prospective clinical trial that will compare IV and oral sedation for multiple ocular sub-specialty procedures. The procedures to be investigated include: cataract, retina, cornea, and glaucoma surgical groups.

Arms: arm 1: The following ocular procedures will fall under this arm of the study:

• Cataracts

Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:

* Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
* Microcrystalline cellulose oral placebo with midazolam intravenous sedation arm 2: The following ocular procedures will fall under this arm of the study:

* Pars plana vitrectomy
* Pars plana vitrectomy with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal

Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:

* Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
* Microcrystalline cellulose oral placebo with midazolam intravenous sedation arm 3: The following ocular procedures will fall under this arm of the study:

* Descemet Stripping Endothelial Keratoplasty (DSEK)
* Cataracts with Descemet Stripping Endothelial Keratoplasty (DSEK)
* Descemet Membrane Endothelial Keratoplasty (DMEK)
* Cataracts with Descemet Membrane Endothelial Keratoplasty (DMEK)
* Conjunctival and/or corneal lesion excisions
* Pterygium

Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:

* Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
* Microcrystalline cellulose oral placebo with midazolam intravenous sedation arm 4: The following ocular procedures will fall under this arm of the study:

* Ahmed valve
* Ahmed valve with cataracts
* Trabeculectomy
* Trabeculectomy with cataracts
* Baerveldt
* Baerveldt with cataracts
* Endocyclophotocoagulation
* Endocyclophotocoagulation with cataracts
* Istent
* Cataracts with istent
* Kahook
* Cataracts with kahook
* Cypass
* Cypass with cataracts

Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:

* Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
* Microcrystalline cellulose oral placebo with midazolam intravenous sedation
Interventions: intervention 1: Triazolam intervention 2: Midazolam intervention 3: Microcrystalline Cellulose intervention 4: Sodium chloride 0.9%
Intervention descriptions: intervention 1: This will be used for oral sedation. This capsule or a microcrystalline cellulose placebo capsule will be administered depending on the randomized treatment group.

Dose for BMI less than 35: 0.125 mg

Dose for BMI greater than or equal to 35: 0.25 mg intervention 2: This will be used for intravenous sedation. This injection or sodium chloride 0.9% will be administered depending on the randomized treatment group.

Dose for BMI less than 35: 1.0 mg

Dose for BMI greater than or equal to 35: 2.0 mg intervention 3: This will be used for the oral placebo. This capsule or a triazolam capsule will be administered depending on the randomized treatment group.

Dose for BMI less than 35: 1 capsule

Dose for BMI greater than or equal to 35: 2 capsule intervention 4: This will be used for the intravenous placebo.This injection or midazolam will be administered depending on the randomized treatment group.

Dose for BMI less than 35: volume to match volume of active intravenous medication

Dose for BMI greater than or equal to 35: volume to match volume of active intravenous medication

Protocol documents:
Prot_SAP_000.pdf: 
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A single-center, randomized, double-blind, double-dummy, parallel-group study 
comparing oral sedation to intravenous sedation for ocular procedures. 
 
ClinicalTrials.gov number: NCT03246724 
Protocol Version Number: 2.5 
Protocol Version Date: 28 February 2019 
Funding Mechanism: Boston Medical Center 
Principal Investigator: Manju Subramanian, MD 
 
 
Phone: (617) 638-4455 
 
 
E-mail: Manju.Subramanian@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 .....................................................................................................................5 
3 Background/Rationale & Purpose..............................................................................................7 
3.1 
Background Information ..................................................................................................7 
3.2 
Rationale and Purpose ......................................................................................................7 
4 Objectives ..................................................................................................................................8 
4.1 
Study Objectives ..............................................................................................................8 
4.2 
Study Outcome Measures .................................................................................................8 
4.2.1 
Primary Outcome Measures ...............................................................................9 
4.2.2 
Secondary Outcome Measures ...........................................................................9 
5 Study Design ..............................................................................................................................9 
6 Potential Risks and Benefits ....................................................................................................10 
6.1 
Risks ...............................................................................................................................10 
6.1.1 
Risk Associated with Patient Comfort and Satsifaction ..................................10 
6.1.2 
Risks Associated with the Benzodiazepine Midazolam ..................................10 
6.1.3 
Risks Associated with the Benzodiazepine Triazolam ....................................11 
6.1.4 
Decreasing Associated Risk with Benzodiazepines Triazolam and 
Midazolam .........................................................................................................................11 
6.1.5 
Risk of Intravenous Cannulation .....................................................................11 
6.1.6 
Risk Associated with Geriatric Patients taking a Benzodiazepine ..................12 
6.1.7 
Risk Associated with Pregnancy and Nursing with a Benzodiazepine ............12 
6.1.8 
Risk of Loss of Confidentiality ........................................................................12 
6.1.9 
Unknown Risks ................................................................................................12 
6.2 
Potential Benefits ...........................................................................................................13 
6.3 
Analysis of Risks in Relation to Benefits .......................................................................13 
7 Study Subject Selection ...........................................................................................................13 
7.1 
Subject Inclusion Criteria ...............................................................................................13 
7.2 
Subject Exclusion Criteria ..............................................................................................14 
8 Study Intervention ....................................................................................................................15 
9 Study Procedures .....................................................................................................................16 
9.1 
Study Schedule ...............................................................................................................16 
9.1.1 
Screening and Consent .....................................................................................16 
9.1.2 
Pre-Procedure and Randomization ..................................................................18 
9.1.3 
Follow-Up Study Visits ...................................................................................18 
9.2 
Early Termination Visit ..................................................................................................19 
9.3 
Non-Study Visits (Unscheduled Visits) .........................................................................19 
9.4 
Masking Procedure .........................................................................................................19 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ...........................................20 
10.1 
Definitions ......................................................................................................................20 
10.2 
Safety Review ................................................................................................................21 
10.3 
Reporting Plans ..............................................................................................................22 
10.4 
Stopping Rules ...............................................................................................................22 
10.5 
Emergency Unmasking ..............................................................................................2322 
11 Data Handling and Record Keeping ........................................................................................23 


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11.1 
Confidentiality ................................................................................................................23 
11.2 
Source Documents ..........................................................................................................23 
11.3 
Case Report Forms .........................................................................................................24 
11.4 
Study Records Retention ................................................................................................24 
12 Statistical Plan ..........................................................................................................................24 
12.1 
Study Hypotheses ...........................................................................................................24 
12.1.1 
Primary Objective: Patient Satisfaction ...........................................................24 
12.1.2 
First Secondary Objective: Surgeon Satisfaction ............................................25 
12.1.3 
Second Secondary Obejctive: Anesthesiologist/CRNA Satisfaction ..............25 
12.1.4 
Third Secondary Objective: Additional Anesthesia Intervention ....................26 
12.1.5 
Fourth Secondary Objective: Surgical Complication Rates ............................26 
12.2 
Sample Size Determination ........................................................................................2726 
12.3 
Statistical Methods .........................................................................................................27 
12.3.1 
Margin on Non-Inferiority ...............................................................................27 
12.3.2 
Primary Outcome .............................................................................................28 
12.3.3 
Secondary Outcomes .......................................................................................28 
13 Ethics/Protection of Human Subjects ......................................................................................28 
14 Literature References ...............................................................................................................30 
15 Appendix ..................................................................................................................................31 
 
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..........................................................................................................31 
15.1 
31 
15.2 
Schematic of Study Design ............................................................................................32 
15.3 
Case Report Forms (CRF) ..............................................................................................33 
15.3.1 
Screening and Consent CRF (Sample) ............................................................33 
15.3.2 
Pre-Procedure and Randomization CRF (Sample) ..........................................47 
15.3.3 
Day of Surgical Procedure CRF (Sample) .......................................................54 
15.3.4 
Post-Operative Day 1 CRF (Sample) ...............................................................74 
15.4 
Midazolam Package Insert .............................................................................................82 
15.5 
Triazolam Package Insert .............................................................................................108 
15.6 
Delirium Questionnaire (Sample) ................................................................................124 
15.7 
Satisfaction Surveys .....................................................................................................125 
15.7.1 
Post-Surgery Anesthesiologist/CRNA Satisfaction Survey (Sample) ...........125 
15.7.2 
Post Surgery Surgeon Satisfaction Survey (Sample) .....................................126 
15.7.3 
Post-Surgery Patient Satisfaction Survey (Sample) .......................................127 
15.8 
AE, SAE, and UP Tracking and Reports .....................................................................129 
15.8.1 
AE, SAE, and UP Report Log (Sample) ........................................................129 
15.8.2 
AE, SAE, and UP Review Log (Sample) ......................................................130 
15.8.3 
SAE and UP Report Form (Sample) ..............................................................131 
15.8.4 
Data Safety Monitoring Report (Sample) ......................................................135 
 
 
 
 


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1 
List of Abbreviations 
 
Abbreviation 
Abbreviation Definition 
AEs 
Adverse events 
BMC 
Boston Medical Center 
BMI 
Body mass index 
BUMC 
Boston University Medical Campus 
CNS 
Central nervous system 
COPD 
Chronic obstructive pulmonary disease  
CRNA 
Certified Registered Nurse Anesthetist 
DMEK 
Descemet membrane endothelial keratoplasty 
DSEK 
Descemet stripping endothelial keratopathy  
FDA 
Food and Drug Administration 
IPS 
Investigational Pharmacy Services 
IRB 
Institutional Review Board 
ISAS 
Iowa Satisfaction with Anesthesia Scale 
IV 
Intravenous 
KPCO 
Kaiser Permanente Colorado 
ml 
Milliliters 
MPR 
Minor procedure room 
OR 
Operating room 
PI 
Principal investigator  
PO 
By mouth 
PPV 
Pars plana vitrectomy 
SAEs 
Serious adverse events 
SOC 
Standard of care 
UP 
Unanticipated problem 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2 
Protocol Summary 
Title: 
A single-center, randomized, double-blind, double-dummy, 
parallel-group study comparing oral sedation to intravenous 
sedation for ocular procedures. 
Population: 
Male and female Boston Medical Center (BMC) patients 18 years 
or older, with a surgical plan within the cataracts, retina, cornea, 
and glaucoma sub-specialties services in the Ophthalmology 
Department 
Interventions: 
Oral medications 
 ACTIVE: Triazolam 0.125mg tablets, over-encapsulated for 
blinding 
 PLACEBO: Microcrystalline cellulose powder capsule to 
match triazolam 
 Dose:  
o BMI < 35: triazolam 0.125 mg/placebo (1 capsule) 
single dose by mouth approximately 30 min prior to 
procedure 
o BMI > 35: triazolam 0.25 mg/placebo (2 capsules) 
single dose by mouth approximately 30 min prior to 
procedure  
Intravenous (IV) medications  
 ACTIVE: Midazolam 1mg/mL injection 
 PLACEBO: Sodium Chloride 0.9% 
 Dose:  
o BMI < 35: midazolam 1mg/placebo (1mL) single 
dose intravenously approximately 5 min prior to 
procedure 
o BMI ≥ 35: midazolam 2mg/placebo (2mL) single 
dose intravenously approximately 5 min prior to 
procedure 
 
Objectives: 
To determine if oral triazolam will provide a non-inferior level of 
patient satisfaction compared to IV midazolam when undergoing 
an ophthalmic surgical procedure. 
Design/Methodology: 
Surgical type 1: cataract procedures 
Surgical type 2: retina procedures 
Surgical type 3: cornea and ocular surface procedures 
Surgical type 4: glaucoma procedures 
 
Arm A: Oral triazolam with IV placebo to match midazolam 
Arm B: Oral placebo to match triazolam with IV midazolam  
 
Subjects will be randomized (1:1) to one of the two study arms 
listed above. On the day of surgery, the subject, 
anesthesiologist/CRNA, and surgeon will be blinded to the 


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treatment assignment. The anesthesiologist/CRNA or pre-operative 
nurse will administer the blinded oral medication approximately 30 
minutes before the procedure beings. The anesthesiologist/CRNA 
or pre-operative nurse will administer the blinded IV medication 
approximately 5 minutes before the procedure begins. At the 
completion of the procedure, the anesthesiologist/CRNA and the 
surgeon will complete a satisfaction survey. The subject will then 
return within 2 days for their first post-operative clinical visit and 
complete a satisfaction survey.  
 
Table 1 in the Appendix can be referenced for the schedule of 
study events.  
Total Study Duration: 
Approximately 1.5 years 
Subject Participation 
Duration: 
Subject participation length is variable based on sub-specialty 
procedures wait times and operating room availability: 
 Cataract: approximately 1-2 months 
 Retina: approximately 1-4 weeks 
 Cornea: approximately 1-2 months 
 Glaucoma: approximately 1-2 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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3 
Background/Rationale & Purpose 
 
3.1 
Background Information 
 
The Department of Ophthalmology at BMC has high demand for clinical visits and operating 
room procedures. As with most academic teaching institutions the operating room is shared with 
other surgical services, and accessibility for operating room space can be challenging. Most 
ocular procedures are short cases often requiring minimal anesthesia, some health care systems 
such as Kaiser Permanente are performing cataract procedures in a minor procedure room 
setting, either connected with an ambulatory surgery center or in a private office, under oral 
sedation with varying degrees of support from an Anesthesiologist. The Kaiser Permanente 
Colorado (KPCO) medical offices in Denver, Colorado have been performing cataract surgery in 
a minor procedure room (MPR) with oral sedation since 2006. They have published their 10-year 
experience reporting retrospectively on over 21,000 cases, stating that their model is safe and 
effective.7 
 
Eye care services at BMC present some unique challenges, when compared to the KPCO 
experience.  The patient population is vulnerable and has often had poor access to healthcare. 
Many patients have more advanced disease upon presentation.  Many patients are also non-native 
English speakers or do not speak English at all.  Additionally, as an academic teaching center 
where trainees assist in surgery, case times are longer than what may be experienced at 
KPCO.7 Additionally, the KPCO experience evaluated only cataract surgery,7 and did not report 
on other ocular surgical cases such as retina, cornea, and glaucoma procedures. 
 
This study aims to compare the role of oral sedation (study group) to IV sedation (control group) 
in ocular procedures in a double-blind, double-dummy fashion.  The primary outcome measured 
will be patient satisfaction.  Secondary outcomes include surgeon satisfaction, anesthesiologist 
satisfaction, and safety. 
 
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  
 
Midazolam is an FDA-approved intravenous medication commonly used as a sedative for ocular 
procedures conducted in the operating room. This study will compare the use of triazolam, an 
FDA-approved oral sedative for the same types of ocular procedures, a purpose which has not 
fully been investigated. The benzodiazepine triazolam was chosen as the oral medication due to 
its similarity to midazolam. The similarities between midazolam and triazolam include similar 
half-life, risks, and patient experience. 6,8 The medication doses were chosen from current SOC 
use based on weight.6,8 The lower dose for both medications are used for patients with a BMI 
less than 35 and the higher dose is used for patients with a BMI greater than or equal to 35.    
 


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This is the first double-blind, prospective clinical trial that will compare IV and oral sedation for 
multiple ocular sub-specialty procedures. The procedures to be investigated are listed in Section 
7.1 of this protocol, which include cataract, retina, cornea, and glaucoma surgical groups.  
 
The purpose of this study is to demonstrate non-inferiority in patient satisfaction between the use 
of IV midazolam and oral triazolam. If the study shows that oral sedation is non-inferior to IV 
sedation, it may allow ocular procedures to be moved from the operating room into a procedure 
room setting in an ambulatory surgery center or office setting. If IV access is deemed 
unnecessary for some or all ocular procedures, then this may obviate the support of an 
anesthesiologist in the operating room. This will be beneficial for patients, as they will have a 
more desirable and uniform sedation experience with less risk of apnea that can be seen with IV 
sedation,8 and since IV insertion will no longer be necessary, it will reduce the risk for IV-
related side effects.3 This benefits BMC by allowing more flexibility and availability of their 
operating rooms for more complex cases and high acuity patients undergoing general anesthesia, 
and could reduce anesthesiology-related costs if they are no longer needed to support eye 
cases.1 Other surgical subspecialties that perform short cases currently under monitored 
anesthesia care could also consider this option in the future.  This also has the potential to reduce 
health care costs in the long run for patients, third party payers, and BMC.1 
 
4 
Objectives 
 
4.1 
Study Objectives 
 
The primary objective of this study is to compare patient satisfaction of oral triazolam to IV 
midazolam when administered for ocular procedures. The ocular procedures being investigated 
are for cataracts, retina, cornea, and glaucoma sub-specialties; a complete list of procedures 
included in this study can be found in Section 7.1 of this protocol. The primary endpoint will be 
measured by the patient satisfaction survey administered at the first post-operative clinic visit. 
The central hypothesis is that oral triazolam is non-inferior to IV midazolam when comparing 
patient satisfaction.  
 
Secondary objectives include anesthesiologist/CRNA and surgeon satisfaction. These 
satisfaction means will be evaluated with an anesthesiologist/CRNA and a surgeon specific 
survey. Another secondary objective is to track the number of patients requiring additional 
anesthesia intervention during the procedure.  And finally, we will track any intra-operative 
complications either related to the surgical procedure or the sedation, to assess patient safety.  
 
4.2 
Study Outcome Measures 
 
Patient, anesthesiologist/CRNA, and surgeon satisfaction will be measured through personnel-
specific satisfaction surveys. The anesthesiologist/CRNA and surgeon satisfaction surveys will 
be administered immediately after the completion of the surgical case. By doing so, this will 
create individualized case feedback and elicit more accurate responses. The patient satisfaction 
survey will be administered during the patient’s first post-operative clinic visit, which occurs one 
or two days after the procedure. The day of the procedure was not chosen as the day to 


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administer the patient satisfaction survey because the patient will still be recovering from the 
effects of the sedation.  
 
All surveys are a variation of the Iowa Satisfaction with Anesthesia Scale (ISAS), which has 
previously been used to measure patient satisfaction for cataract procedures by the KCPO.5, 7 All 
satisfaction surveys are on a scale from 1 (least satisfied) to 6 (most satisfied). For each survey, 
every question’s response will be independently scored from 1 to 6. All of the responses per 
survey will then be independently averaged to generate an individualized satisfaction score for 
the procedure. The individualized overall satisfaction score will be on the same 1-to-6 scale. 
Each sub-specialty surgical group of the study will be analyzed separately to determine non-
inferiority between the two intervention groups.  
 
Additional anesthesia intervention will be analyzed by calculating the number of subjects in each 
surgical group that receive additional anesthetic agents during the operative procedure after the 
initial sedation. Lastly, complication rates will be compared in order to determine the level of 
patient safety for each surgical procedure type.  
 
Reference Section 12.0 for further statistical analysis explanations.  
 
Reference Appendix Section 15.7 for patient and personnel-specific satisfaction surveys. The 
scoring guides can be found within Appendix Sections 15.4.3 and 15.4.4. 
 
4.2.1 Primary Outcome Measures 
 
The objective of this study is to assess the patient satisfaction of patients administered oral 
triazolam during ocular procedures. 
 
4.2.2 Secondary Outcome Measures 
 
The following secondary outcomes will also be measured: 
1. Surgeon satisfaction score 
2. Anesthesiologist/CRNA satisfaction score 
3. Total additional anesthesia interventions 
4. Total surgical complications  
 
5 
Study Design 
 
This clinical trial is a prospective, single center, randomized, controlled study. A total of up to 
400 subjects will be randomized, stratified by surgical groups (cataracts, retina, cornea, and 
glaucoma), in a 1:1 ratio with approximately 200 subjects randomized to receive the oral 
sedation and approximately 200 subjects randomized to receive the IV sedation. Subjects will be 
randomized based on the procedures outlined in Section 9.1.2. Subjects have an equal chance of 
being randomized to one of the following study arms: 
 Arm A: Oral triazolam with placebo to match IV midazolam 
 Arm B: Oral placebo to match triazolam with IV midazolam 


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The primary endpoint is the patient satisfaction score. This satisfaction score is defined as the 
overall average of the twelve scored survey questions, which will be completed at the patient’s 
first pre-operative clinic visit. The secondary endpoints include anesthesiologist/CRNA and 
surgeon satisfaction during the surgical case. Furthermore, it will be analyzed if any additional 
anesthesia intervention was needed throughout the surgical procedure and if any complications 
occurred during the procedure. 
 
Reference Appendix for a schematic of the study design in Section 15.2.  
 
6 
Potential Risks and Benefits 
 
6.1 
Risks  
 
6.1.1 Risk Associated with Patient Comfort and Satsifaction 
 
Oral sedation has not been extensively investigated as a substitute for IV sedation for SOC 
ocular surgical procedures. One risk with the transition of sedation routes is a change in the level 
of patient comfort and ultimately their satisfaction with the procedure. In order to maximize 
patient safety, comfort and satisfaction, the study will be conducted at the Moakley OR 
ambulatory surgery center with monitored anesthesia support as is currently done for all BMC 
SOC patients. The decision to administer additional IV medication will occur at the discretion of 
the attending surgeon, in consultation with the anesthesiologist or CRNA, based on their 
assessment of the patient’s level of comfort during the procedure. This will allow the 
anesthesiologist/CRNA to administer additional medication when needed to ensure patient 
comfort.  
 
6.1.2 Risks Associated with the Benzodiazepine Midazolam 
 
Midazolam is utilized as sedation for SOC ocular surgical procedures in all age groups. If the 
patient is thought to be at a higher risk for developing any of the complications that could occur 
from midazolam, they will not be able to participate in the study. 
  
Most Common Risks  
The most common side effects of midazolam are difficulty with regular thoughts and functions, 
difficulty breathing, and an allergic reaction causing nausea or vomiting. Midazolam has shown 
a high incidence of partial or complete impairment for the next several hours after 
administration. The decision to allow patients to return to regular activities requiring complete 
mental alertness, operate hazardous machinery or drive a motor vehicle is individualized.8 
  
Other Adverse Events  
Other reactions such as agitation, involuntary movements (including tonic/clonic movements and 
muscle tremor), hyperactivity and combativeness have been reported. These reported reactions 
could be due to inadequate or excessive dosing or improper administration.8 


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Debilitation and Comorbid Considerations  
Adults with COPD have shown to be sensitive to the respiratory depressant effect of midazolam. 
Adults with chronic renal failure or congestive heart failure eliminate midazolam more slowly.8 
 
Reference Appendix Section 15.4 for the complete midazolam package insert. 
 
6.1.3 Risks Associated with the Benzodiazepine Triazolam 
 
If the patient is thought to be at a higher risk for developing any of the complications that could 
occur from triazolam, they will not be able to participate in the study. 
  
Most Common Risks 
The most common risks of triazolam are difficulty with regular thoughts and functions, sleeping 
problems, or an allergic reaction causing difficulty breathing, nausea, vomiting, and airway 
closure. Triazolam has shown a high incidence of partial or complete impairment for the next 
several hours after administration. The decision to allow patients to return to regular activities 
requiring complete mental alertness, operate hazardous machinery or drive a motor vehicle is 
individualized.6 
  
Risk of Abnormal Thinking/Behavior 
The emergence of new thinking/behavior abnormalities and sleep disturbances can be the 
consequence of an unrecognized psychiatric physical disorder. Some of these changes are 
characterized by decreased inhibition, like aggressiveness and extroversion that may seem 
excessive. Other behavioral changes include bizarre behavior, agitation, hallucinations, 
depersonalization, worsening depression, and suicidal thoughts. Some of these findings have 
been seen with administration of triazolam. The use of alcohol and other CNS depressants with 
triazolam can increase the risk of these behaviors.6 
  
Triazolam Interaction with Medications that Inhibit Metabolism via Cytochrome P450 3A 
Drugs that inhibits the initial step in triazolam metabolism may have an effect of the clearance of 
the medication.6 
 
Reference Appendix Section 15.5 for the complete triazolam package insert. 
 
6.1.4 Decreasing Associated Risk with Benzodiazepines Triazolam and Midazolam 
 
In order to decrease any associated risk, the exclusion criteria will eliminate any patient with 
known problems when taking a benzodiazepine. Furthermore, there will be anesthesia 
intervention available from the time the study medications are administered to the time the 
patient is cleared for discharge. Any adverse or unanticipated events will be addressed 
immediately by the anesthesiologist and the medical team.  
 
6.1.5 Risk of Intravenous Cannulation 
 


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Patients receiving oral sedition do not typically also receive an IV line. Complications associated 
with an IV line include infection, phlebitis and thrombophlebitis, emboli, pain, hematoma or 
hemorrhage, extravasation, arterial cannulation and needle stick injuries.3 Only specific study 
personnel with the required medical training will be designated tasks associated with 
administering the oral and IV medications. 
 
6.1.6 Risk Associated with Geriatric Patients taking a Benzodiazepine 
 
Additionally, geriatric patients are at higher risk for the development of delirium after 
administration of benzodiazepines.6,8 In order to reduce this risk, all patients 70 years of age or 
older will complete a delirium pre-screening questionnaire as demonstrated in Appendix Section 
15.6. The questionnaire mimics pre-operative clearance screening already in place for geriatric 
patients as SOC.4 If patients do not pass the delirium questionnaire pre-screen they will not be 
able to participate in the study. With these safe guards in place, patients with increased 
benzodiazepine vulnerability will be screened out of study participation, and those that pass the 
screening will be at a much lower risk of experiencing delirium. 
 
Reference Appendix Section 15.6 for the complete delirium pre-screening questionnaire. The 
scoring guide can be found in the Screening and Consent CRF located in Appendix Section 
15.3.1. 
 
6.1.7 Risk Associated with Pregnancy and Nursing with a Benzodiazepine 
 
Benzodiazepines, like triazolam and midazolam, can be harmful to a fetus.6,8 In order to 
eliminate this risk all women who are pregnant or have a positive pregnancy test on the day of 
surgery will be ineligible to participate. It is SOC to administer urine pregnancy tests to all 
patients who are childbearing age, prior to their procedure.4 Additionally, triazolam and 
midazolam are excreted in breast milk, which could pose a risk the infant.6,8 For this reason, all 
women who are nursing will not be able to participate in this study.  
 
6.1.8 Risk of Loss of Confidentiality 
 
There is the unlikely possibility of breach of confidentiality. Confidentiality will be protected as 
stated in Section 11.1 of this protocol.  
 
6.1.9 Unknown Risks 
 
There may be unknown risks or discomforts involved. Study staff will update all subjects in a 
timely manner with any new information that may affect their health, welfare, or decision to 
participate in this study.  


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6.2 
Potential Benefits 
 
If the study shows that oral triazolam is non-inferior to IV midazolam, this may allow ocular 
surgeries to be performed under oral sedation and reduce the need for the use of IV medication.  
If IV access is deemed unnecessary for some or all ocular procedures, then this may obviate the 
need for anesthesiologist or CRNA support in the operating room, and patients may be 
monitored by a registered nurse instead. Potential benefits to patients are that oral sedation may 
provide a more desirable and uniform effect with less risk of nausea, vomiting and apnea than 
can be seen with IV sedation.  This will also result in elimination of the risk for IV-related side 
effects, such as pain from extravasation of medication into the surrounding soft tissue as well as 
infection at the IV site.3,8 Fasting on the day of surgery would not be required if oral sedation 
alone is used for ocular surgeries. Currently, patients are not allowed to eat or drink anything 
after midnight on the day of surgery2, causing some of our patients fast for more than 12 hours.  
This will likely improve the patient’s surgical experience by reducing the discomfort associated 
with fasting  
 
Potential benefits to BMC include increasing the availability of existing OR spaces for more 
complex cases and higher acuity patients undergoing general anesthesia, increasing the 
efficiency and cost-effectiveness of ocular surgery cases, and possibly reducing anesthesiology-
related costs if their role in supporting ocular surgery cases is reduced.1 This will allow greater 
flexibility to surgeons and patients and help meet current demand for eye care services.  This 
also has the potential to reduce health care costs in the long run for patients, third party payers, 
and BMC.1 
 
6.3 
Analysis of Risks in Relation to Benefits 
 
Oral triazolam was selected due to its similar effects and risks to IV midazolam,6,8 thus eliciting 
a similar procedural level of risk as noted above.  
 
If the study demonstrates that oral triazolam is an acceptable substitution for IV midazolam, then 
patients undergoing eye surgery will have less exposure to IV-related risks, elimination of same 
day fasting, improved access to eye care, decreased procedural costs, and decreased wait time for 
elective eye surgery.  The benefits of potentially changing the standard of sedation for eye 
surgery will outweigh the risks of participation in the study.    
 
7 
Study Subject Selection 
 
7.1 
Subject Inclusion Criteria 
 


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In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
 Inclusion criteria 
 Age 18 years or older 
 Ability to speak and read in English or Spanish or Haitian-Creole 
 Subjects able to consent for themselves 
 Outpatient surgical plan for any of the following procedures: 
 Cataract Surgery 
 Cataracts 
 Retina 
 PPV 
 PPV with cataracts, epiretinal membrane peel, pars plana 
lensectomy and/or endolaser 
 Silicone oil removal 
 Cornea 
 DSEK 
 Cataracts with DSEK  
 DMEK 
 Cataracts with DMEK 
 Conjunctival and/or corneal lesion excisions  
 Pterygium 
 Glaucoma 
 Ahmed valve 
 Ahmed valve with cataracts 
 Trabeculectomy 
 Trabeculectomy with cataracts 
 Baerveldt 
 Baerveldt with cataracts 
 Endocyclophotocoagulation 
 Endocyclophotocoagulation with cataracts 
 Istent 
 Istent with cataracts 
 Kahook 
 Kahook with cataracts 
 Cypass 
 Cypass with cataracts 
 
7.2 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
 Exclusion criteria 


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 Surgical plan which includes general anesthesia 
 Hypersensitivity or allergy to benzodiazepines 
 Women who are pregnant, have a positive pregnancy test on the day of surgery, 
refuse a pregnancy test, or are nursing 
 Previous delirium after anesthesia with a benzodiazepine 
 Subjects 70 years of age or older who fail the delirium pre-screening 
questionnaire as shown in Appendix Section 15.6 
 Currently experiencing the effects of drugs/alcohol 
 Current oral/IV regimen of any medication inhibiting cytochrome P450 3A which 
includes ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelavir, 
saquinavir, and lopinavir  
 Subjects already enrolled in this study for the fellow eye 
 Subjects enrolled in a clinical trial with an investigational drug within the past 3 
months 
 Failed anesthesia clearance to receive a benzodiazepine 
 
8 
Study Intervention 
 
Arm A: Oral triazolam with IV placebo to match midazolam 
Arm B: Oral placebo to match triazolam with IV midazolam  
 
Oral medications 
 ACTIVE: Triazolam 0.125mg tablets, over-encapsulated for blinding 
 PLACEBO: Microcrystalline cellulose powder capsule to match triazolam 
 Dose:  
o BMI < 35: 0.125 mg (1 capsule) single dose by mouth approximately 30 min prior 
to procedure 
o BMI ≥ 35: 0.25 mg (2 capsules) single dose by mouth approximately 30 min prior 
to procedure  
Intravenous medications  
 ACTIVE: Midazolam 1mg/mL injection 
 PLACEBO: Sodium Chloride 0.9% 
 Dose:  
o BMI < 35: 1mL (1mg) single dose intravenously approximately 5 min prior to 
procedure 
o BMI ≥ 35: 2mL (2mg) single dose intravenously approximately 5 min prior to 
procedure 
IPS will be responsible for: 
 Ordering the investigational products 
 Receipt, storage, accountability, dispensing, destruction and record keeping for all 
investigational products 
 Preparation of blinded doses 
 Receipt and documentation of any unused doses 
 


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Reference Appendix Sections 15.4 for formulation, packaging, and labeling information about 
midazolam. 
 
Reference Appendix Sections 15.5 for formulation, packaging, and labeling information about 
triazolam. 
 
9 
Study Procedures 
 
The following study procedures will be performed for study-specific purposes: 
 Review of inclusion/exclusion criteria for eligibility 
 Informed consent 
 Collection of demographic information 
 Study specific medical and ophthalmic history  
 Delirium pre-screening questionnaire for subjects 70 years of age or older 
 Randomization: eligible subjects will be randomized to receive either Arm A or Arm B 
medications 
 Dispense and administration of medication based on randomization 
 Completion of survey by attending surgeon after surgical case 
 Completion of survey by anesthesiologist/CRNA after surgical case 
 Completion of survey by subject at the first post-operative clinical visit (+ 2 days of 
surgery) 
 Collection of information regarding anesthesia intervention and surgical complications 
 Collection of information regarding any AEs, SAEs, or UPs  
 
The following procedures will be performed as SOC: 
 Ophthalmic exam prior to surgery 
 Planned outpatient surgical procedure  
 Preoperative clearance 
 Urine pregnancy test (if required) 
 Ophthalmic exam approximately one day after surgery 
 
9.1 
Study Schedule 
 
9.1.1 Screening and Consent 
 
Cataract, retina, cornea, or 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 


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 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 at a visit 
to the eye clinic or at the Moakley PACU on the day of the surgical 
procedure: 
o Both the patient and the investigator or the designated study team 
member conducting the consent form will sign 
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: 
 
Manju Subramanian, MD 
Principal Investigator 
Manju.Subramanian@bmc.org 
(617) 638-4555 
 
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  
 
 Study-specific review of medical record and demographics 
 Schedule pre-operative clearance appointment 
 Schedule surgical procedure 
 
Alternatively, patients who may not be getting their surgery for 2-3 months may be contacted by 
a letter with a follow-up phone call 1 month prior to their surgery date regarding participation in 
the study. The patient will be given the option to discuss study participation at their next SOC, 
pre-operative clinical visit, set-up a separate study participation discussion visit, or discuss 
participation on the day of their procedure. If desired, a consent form will be mailed to the 
patient to review at home. Depending on how the patient would like to proceed with their 
participation, consent will be obtained during the SOC clinical visit, the study participation visit, 
or on the day of surgery. If the research team is unable to contact the patient by telephone or in 
clinic at a SOC appointment prior to the day of surgery, the research team will approach them on 
the day of surgery upon their arrival to the hospital to explain and discuss participation in the 
study.  
 


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If a subject has provided written informed consent and is 70 years of age or older, a delirium 
screening questionnaire will be administered in clinic during a SOC visit, a visit set-up to discuss 
study participation, or on the day of the procedure. All subjects in this age group are required to 
pass the delirium screening questionnaire in order to continue with enrollment. 
 
If a woman of child bearing potential has provided written informed consent, a urine pregnancy 
test will be ordered to be completed on the day of surgery. 
9.1.2 Pre-Procedure and Randomization 
 
For the pre-procedure and randomization procedures, the following will be completed: 
 Study-specific review of inclusion/exclusion criteria 
 Preoperative clearance confirmation: Approximately 1-2 weeks from 
enrollment for retina procedures, and 1-3 months from randomization for all 
other procedures 
o Before the scheduled day of surgery, the subject must complete their 
individualized preoperative clearance plan. 
 Confirm surgical procedure date 
 Randomization: After screening, subjects who meet eligibility criteria will be 
randomly assigned to Arm A or Arm B based on the randomization tables, 
generated by the statistician, stratified by type of surgical group using a 
blocking scheme with a block size of 6.  
o Each randomization spot will be assigned a randomization ID of four 
numbers. The first number will indicate the surgical group, while the 
last three numbers will be the randomization number. The 
randomization ID will be paired with the subject ID at the time of 
randomization.  
o The randomization records will be placed in sealed envelopes by the 
statistician to ensure that data collection is completed in a blinded 
fashion. When an eligible subject is enrolled and ready to be 
randomized, the study team will select the sealed envelope with the 
randomization ID written on the outside to be readily available in case 
of an emergency.  IPS will have a copy of the unblinded 
randomization table in order to match the randomization ID with the 
appropriate treatment arm. 
 
9.1.3 Follow-Up Study Visits 
 
Day of Surgery: Within 30 days of preoperative clearance 
On the scheduled day of surgery, the following will be completed: 
 Confirmation of eligibility and pre-operative clearance 
 Urine pregnancy test (if required) 
 Administration of randomized oral Arm A or Arm B medication by the 
blinded anesthesiologist/CRNA or pre-operative nurse  


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o This will occur approximately 30 minutes before the start of 
the subjects surgical procedure 
 Administration of randomized intravenous Arm A or Arm B 
medication by the blinded anesthesiologist/CRNA or pre-operative 
nurse  
o This will occur approximately 5 minutes before the start of the 
subjects surgical procedure in the OR 
 The surgical case will be completed as planned 
o The local anesthetic used during each case and the route of 
administration will be determined by the surgeon according to 
SOC, and the information recorded.  
o If the subject requires additional anesthetic, this can be 
administered at the surgeon’s discretion and will be recorded 
for research purposes 
 At the completion of the case, the anesthesiologist/CRNA and 
attending surgeon will be given a satisfaction survey to complete prior 
to moving onto the next case 
 Assessment of possible AEs, SAEs, and UPs 
 Information regarding additional anesthesia medication administration 
and case complications with be collected 
 
Final Study Visit; Post-Operative Visit Day 1: Within 2 days after surgery 
 
The following procedures will be completed at the post-operative day 1 visit 
 Subject will complete a satisfaction survey independently 
o Subjects may ask a study team member for language 
clarification as needed 
 Assessment of possible AEs, SAEs, and UPs 
 Dispense $25 travel expense reimbursement 
 Study participation is complete and the subject will complete the 
remainder of their post-operative appointments as scheduled for 1 
week and 1 month from the day of their procedure 
 
9.2 
Early Termination Visit 
 
The subject can be terminated early from the study if their surgical case is canceled and 
not rescheduled. Cancellation of a surgical case could be due to, but is not limited to, no 
longer requiring surgery, non-compliance with preoperative instructions, non-compliance 
with surgical procedure instructions, illness, death, etc. 
 
9.3 
Non-Study Visits (Unscheduled Visits) 
 
At non-study visits a standard office ophthalmology exam will be completed.  
 
9.4 
Masking Procedure 


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All investigators, as well as other physicians, residents and study personnel who may come in 
contact with study subjects will be masked to treatment assignments during data collection. The 
statistician will create the blinded randomization tables which will be shared with IPS to ensure 
the correct study drug will be administered to each patient at each visit. Sealed envelopes will be 
made by the statistician which will have the randomization ID on the outside, and the treatment 
group on the inside. These envelopes will remain sealed during data collection, unless 
emergency unmasking is necessary. 
 
Reference Appendix Section 15.1 for the schedule of events. 
 
Reference Appendix Section 15.3 for the complete CRF used for all study visits which include 
the delirium questionnaire and satisfaction survey scoring guides. 
 
Reference Appendix Section 15.6 for the Delirium Questionnaire. 
 
Reference Appendix Section 15.7 for the patient and personnel-specific satisfaction surveys.  
 
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.  
 


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Unanticipated Problem (UP) 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: 
 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 15.8.1 
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 15.8.3 will be completed for all SAEs and UPs.     
 
The PI will be notified within 1 week of any events determined an AE or SAE and 2 days of any 
event determined a UP. The PI will review all AEs/SAEs within 2 weeks and all UPs within 5 
days.  The PI will consult with the delegated safety monitor, Dr. Stephen Christiansen, as 
applicable after review of the event. After this review, any recommended changes will be made 
to the co-investigators in addition to the BUMC IRB as deemed necessary by the PI.  
 
An interim safety review will take place every 3 to 4 months in which a statistician will consult 
with the delegated safety monitor to discuss any increased rates of AEs, SAEs, or UPs that are 
not typically seen in usual SOC. A report of this meeting will be created, as demonstrated in 
Appendix Section 15.8.4, and made available to the PI and co-investigators for their review. All 
findings determined from the interim safety review will be reported to the BUMC IRB based on 
Section 10.3 of the protocol.  
 


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A safety review will be conducted by the PI, co-investigators, and the safety monitor every 
month during the active recruitment phase of the study. During this review, any questions or 
concerns regarding dosage adjustment, optimization, and safety of oral or IV sedation will be 
addressed by co-investigators or other study personnel. None of the blinded investigators will be 
unblinded during this review. Investigators may be unblinded if a significant number of adverse 
events occur or the PI, in consultation with the safety monitor, chooses to do so because patient 
safety could not be appropriately discussed otherwise.   
 
Reference Appendix Section 15.8 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: 
 SAE, or UP resulting from the administered study intervention such as an allergic reaction 
or breathing problems 
 A positive pregnancy test 
 Failure to complete the require pre-operative clearance 
 Failure to comply with pre-operative instructions 
 Emergency unmasking resulting from an SAE or UP 
 
The study will be stopped if the safety monitor, Dr. Stephen Christiansen, in consultation with 
the statistician, determine that the number of AEs, SAE, and/or UPs exceed that of SOC ocular 
procedures.   
 


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10.5 Emergency Unmasking 
 
Any member of the medical team caring for study subjects in emergency situations may 
determine that unmasking is necessary for clinical care.  
 
If the subject’s randomized intervention was unmasked, it will be included in the electronic 
medical record along with and explanation as to why unmasking was necessary for the subject’s 
clinical care. 
 
Investigational Pharmacy and the statistician will maintain the randomization table and if 
emergency unmasking is required will be available to unmask the treatment. 
 
Events that are so substantial in treating the subject that the PI or co-investigator has deemed 
emergency unmasking necessary or have led to emergency unmasking or a subject, this will be 
reported as an SAE or UP to the BMC/BUMC IRB in accordance with Section 10.3 
 
11 Data Handling and Record Keeping 
 
11.1 Confidentiality 
 
Only the clinical research staff in the Department of Ophthalmology will view patient identifiers 
for eligibility review. Once the patient is consented into the study they will be given a unique 
study-specific identification code. Subject identifiers and the study identification code will be 
linked in a secure password-protected master database located in a departmental networked 
server 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 15.3 
 Delirium questionnaires in Appendix Section 15.6 


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 Patient and personnel specific satisfaction surveys in Appendix Section 15.7 
 AE, SAE, and UP tracking and reports in Appendix Section 15.8 
Data generated by the methods described in the protocol will 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 blue or 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 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 15.3 for the Screening and Consent, Pre-Procedure and 
Randomization, Day of Surgery, and Post-Operative Day 1 CRFs.  
 
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 hardcopy, 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: Patient Satisfaction 
 
Formal hypothesis: Mean patient satisfaction score will be non-inferior when given oral 
triazolam in comparison to the mean patient satisfaction score of IV midazolam during ocular 
procedures. 
 
Testable hypothesis: Patient satisfaction mean will be non-inferior when given oral triazolam in 
comparison to IV midazolam during all basic cataracts, retina, cornea, and glaucoma ocular 
procedures. 
 


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Null hypothesis: The null hypothesis is that the oral sedation group will have a primary endpoint 
mean equal to or less than that of the IV sedation group by the non-inferiority margin or more. 
 
Alternate hypothesis: The alternative hypothesis is that the oral sedation group will have a 
primary endpoint mean higher than the IV sedation group rate minus the non-inferiority margin. 
Specifically: 
𝐻0: 𝜇𝑂< 𝜇𝐼𝑉−𝛿 
𝐻𝐴: 𝜇𝑂≥𝜇𝐼𝑉−𝛿 
Where 𝜇𝑂 is the true mean satisfaction score for the oral sedation,  𝜇𝐼𝑉 is the true mean 
satisfaction score for the IV sedation arm, and 𝛿 is the non-inferiority margin. 
 
12.1.2 First Secondary Objective: Surgeon Satisfaction 
 
Formal hypothesis: Mean surgeon satisfaction score for oral triazolam will not be statistically 
significant in comparison to mean surgeon satisfaction score for IV midazolam during ocular 
procedures. 
 
Testable hypothesis: Mean surgeon satisfaction score for oral triazolam will not be statistically 
significant in comparison to mean surgeon satisfaction score for IV midazolam during all 
cataracts, retina, cornea, and glaucoma ocular procedures. 
 
Null hypothesis: Mean surgeon satisfaction score for oral triazolam will be statistically 
significant in comparison to mean surgeon satisfaction score for IV midazolam during all 
cataracts, retina, cornea, and glaucoma ocular procedures. 
 
Alternate hypothesis: Mean surgeon satisfaction score for oral triazolam will not be statistically 
significant in comparison to mean surgeon satisfaction score for IV midazolam during all 
cataracts, retina, cornea, and glaucoma ocular procedures. 
 
12.1.3 Second Secondary Obejctive: Anesthesiologist/CRNA Satisfaction 
 
Formal hypothesis: Mean anesthesiologist/CRNA satisfaction score for oral triazolam will not be 
statistically significant in comparison to mean anesthesiologist/CRNA satisfaction score for IV 
midazolam during ocular procedures. 
 
Testable hypothesis: Mean anesthesiologist/CRNA satisfaction score for oral triazolam will not 
be statistically significant in comparison to mean anesthesiologist/CRNA satisfaction score for 
IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 


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Null hypothesis: Mean anesthesiologist/CRNA satisfaction score for oral triazolam will be 
statistically significant in comparison to mean anesthesiologist/CRNA satisfaction score for IV 
midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 
Alternate hypothesis: Mean anesthesiologist/CRNA satisfaction score for oral triazolam will not 
be statistically significant in comparison to mean anesthesiologist/CRNA satisfaction score for 
IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 
12.1.4 Third Secondary Objective: Additional Anesthesia Intervention 
 
Formal hypothesis: The total additional anesthesia interventions for oral triazolam will not be 
statistically significant in comparison to total additional anesthesia interventions for IV 
midazolam during ocular procedures. 
 
Testable hypothesis: The total additional anesthesia interventions for oral triazolam will not be 
statistically significant in comparison to total additional anesthesia interventions for IV 
midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 
Null hypothesis: The total additional anesthesia interventions for oral triazolam will be 
statistically significant in comparison to total additional anesthesia interventions for IV 
midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 
Alternate hypothesis: The total additional anesthesia interventions for oral triazolam will not be 
statistically significant in comparison to total additional anesthesia interventions for IV 
midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures. 
 
12.1.5 Fourth Secondary Objective: Surgical Complication Rates 
 
Formal hypothesis: The total surgical complications for oral triazolam will not be statistically 
significant in comparison to total surgical complications for IV midazolam during ocular 
procedures. 
 
Testable hypothesis: The total surgical complications for oral triazolam will not be statistically 
significant in comparison to total surgical complications for IV midazolam during all cataracts, 
retina, cornea, and glaucoma ocular procedures. 
 
Null hypothesis: The total surgical complications for oral triazolam will be statistically 
significant in comparison to total surgical complications for IV midazolam during all cataracts, 
retina, cornea, and glaucoma ocular procedures. 
 


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Alternate hypothesis: The total surgical complications for oral triazolam will not be statistically 
significant in comparison to total surgical complications for IV midazolam during all cataracts, 
retina, cornea, and glaucoma ocular procedures. 
12.2 Sample Size Determination 
A mean standard care satisfaction score of 5.5 with a standard deviation of 1 for the intravenous-
first "standard" treatment, values consistent with prior literature.1 The following assumptions are 
made in the sample size calculation  
 True mean patient satisfaction is 5.5 in both treatment groups  
 Power is 90%.  
 0.5 is the absolute non-inferiority margin  
 Standard deviation of the score 0.75 
 5% One-sided type I error  
Rejection of the null hypothesis will signify that the oral sedation is not inferior to the IV 
sedation with regards to the patient satisfaction score. 
A total of 80 subjects (40 in the oral sedation group and 40 in the IV sedation group) will have 
90% power to reject the above null hypothesis in favor of the alternative under the stated 
assumptions. To account for possible missing data (expected to be approximately 20%), a total of 
100 subjects will need to be randomized. 
 
Since each study intervention group will require a total of 50 subjects within each study arm, this 
means each surgical group will have a total of 100 subjects. There are four study surgical 
outcome groups in this study, totaling up to 400 subjects for the entire project.  
 
400 subjects over the projected 11 months of recruitment is a feasible number because the 
subjects’ active length of study participation is over the course of 2-3 days.  Additionally, the 
ophthalmology department operates on over 2000 cases per year, 58% of which are cataract 
surgery cases.  Recruitment rates in the different surgical groups will vary, as it is anticipated 
that since cataract surgery has the highest case volume, the cataract group will complete 
recruitment prior to the other surgical groups of the study.  In terms of research support staffing, 
there will also be one study team member whose only responsibility is to consent and maintain 
this study, with a possible additional part time volunteer. They will also have the assistance of 
the rest of the study team as needed. 
 
12.3 Statistical Methods 
 
12.3.1 Margin on Non-Inferiority 
 
Non-inferiority margin is a value that defines the magnitude of the amount that is not of practical 
importance. In our pilot study we found the mean patient satisfaction with IV sedation to be 5.5. 
This corresponds to a score between “Very Satisfied” and “Satisfied”. A non-inferiority margin 


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of 0.5, will assure that, if non-inferiority is proven, the mean patient satisfaction with oral 
sedation will correspond to scores corresponding to satisfied or higher. We determined a 0.5 
margin to be considered clinically similar enough to declare non-inferiority because it allows for 
expected patient satisfaction variability, and demonstrates ample justification for providers to 
offer oral sedation as a safe alternative.  
 
12.3.2 Primary Outcome 
 
Patient satisfaction scores. The mean satisfaction score of the oral sedation study group will be 
analyzed and compared to the mean satisfaction score of the IV sedation study group within 
surgical types using a t-test for non-inferiority in order to determine non-inferiority with a non-
inferiority margin of 0.5.  
 
As a sensitivity analysis, an ANCOVA model will be fit to the data adjusting for factors that are 
out of balance following randomization. The mean difference between the adjusted means will 
be calculated. If the lower bound of the 90% two-sided Confidence Interval of mean difference is 
higher than -0.5, the oral sedation will be deemed non-inferior to IV sedation. 
 
12.3.3 Secondary Outcomes 
 
Surgeon satisfaction score, and anesthesiologist/CRNA satisfaction score will be independently 
analyzed. Summary statistics including, means, standard deviations along with points estimates 
of the mean difference between the two groups and 90% Confidence Intervals. 
 
Additional anesthesia intervention will be using summary statistics including, counts and 
proportions along with point’s estimates of the proportion difference between the two groups and 
90% Confidence Intervals. 
 
Surgical complications will be using summary statistics including, counts and proportions along 
with point’s estimates of the proportion difference between the two groups and 90% Confidence 
Intervals. 
 
Each surgical procedure type is anticipated to complete enrollment at varying time points 
throughout the entire study. Once one surgical group type has completed recruitment, it will be 
closed and data and statistical analysis will begin, even if it occurs prior to completion of 
recruitment of the other surgical study groups. By doing so, the study team will be able to 
provide to BMC with results by surgical case type in a timely fashion, which may allow for 
operational decisions regarding OR space allocation to be made. 
 
The primary analysis will be analyzing subjects according to the group they were randomized 
(Intention To Treat (ITT)). In secondary analyses, subjects will be analyzed according to the 
treatment they received (Per Protocol (PP)). 
 
13 Ethics/Protection of Human Subjects 
 


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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 BMC 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. Ambulatory Surgery Center Association. Commercial Insurance Costs Savings in 
Ambulatory Surgery Center 2016; Available from: 
http://www.advancingsurgicalcare.com/reducinghealthcarecosts/costsavings/healthcarebl
uebookstudy. Accessed August 13, 2017. 
2. American Society of Anesthesiologists Committee. Practice guidelines for preoperative 
fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: 
application to healthy patients undergoing elective procedures: an updated report by the 
American Society of Anesthesiologists Committee on Standards and Practice Parameters. 
Anesthesiology. 2011 MAR:114(3):495-511. doi: 10.1097/ALN.0b013e3181fcbfd9. 
3. Campbell J. Intravenous cannulation: potential complications. Prof. Nurse. 1997 May; 12 
(8 Suppl): S10-3. Review. 
4. Committee on Standards and Practice Parameters, Apfelbaum JL, Connis RT, 
Nickinovich DG; American Society of Anesthesiologists Task Force on Preanesthesia 
Evaluation, Pasternak LR, Arens JF, Caplan RA, Connis RT, Fleisher LA, Flowerdew R, 
Gold BS, Mayhew JF, Nickinovich DG, Rice LJ, Roizen MF, Twersky RS. Practice 
advisory for preanesthesia evaluation: an updated report by the American Society of 
Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012 Mar; 
116(3):522-38. doi: 10.1097/ALN.0b013e31823c1067. 
5. Fung D, Cohen M, Stewart S, Davies A. Can the Iowa Satisfaction with Anesthesia Scale 
be used to measure patient satisfaction with cataract care under topical local anesthesia 
and monitored sedation at a community hospital? Anesthesia & 
Analgesia. 2005;100(6):1637–1643. 
6. Greenstone LLC Browser [Internet]. Peapack (NJ): Greenstone LLC Product Database; 
2017- Triazolam Tablets, USP CIV; [cited 2017 Jul 31]; [about 16 p.]. Available from: 
http://labeling.greenstonellc.com/showlabeling.aspx?id=917  
7. Ianchulev T, Litoff D, Ellinger D, Stiverson K, Packer M. Office-Based Cataract 
Surgery: Population Health Outcomes Study of More than 21 000 Cases in the United 
States. Ophthalmology. 2016 Apr;123(4):723-8. doi: 10.1016/j.ophtha.2015.12.020. Epub 
2016 Jan 22. 
8. West-Ward Pharmaceuticals Browser [Internet]. Eatontown (NJ): West-Ward 
Pharmaceuticals Product Database; 2017- Midazolam Hydrochloride Injection, USP C-
IV; [cited 2017 Jul 31]; [about 2 p.]. Available from: http://www.west-
ward.com/sitecore/content/Sites/WestWardPublicSite/Home/Products/ProductsRoot/Mid
azolam%20Hydrochloride%20Injection%20USP%20C-IV 
 
 
 
 
 


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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 be completed at each 
study visit. 
Procedures 
Screening and 
Consent 
Pre-Procedure and 
Randomization 
Day of 
Surgery 
1 day Post-
Operative 
Clinic 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 
 
Pregnancy Test (if required) 
 
 
X 
 
Delirium Pre-Screening 
Questionnaire 
X 
 
 
 
Randomization 
 
X 
 
 
Schedule/Confirm Pre-
operative Clearance 
X 
X 
X 
 
Schedule/Confirm Surgical 
Procedure 
X 
X 
 
 
Coordinate with IPS 
X 
X 
X 
 
Medication is dispensed 
 
 
X 
 
Medication is administered to 
subject 
 
 
X 
 
Assessment and 
documentation of additional 
anesthesia interventions 
 
 
X 
 
Assessment and 
documentation of 
intraoperative complications 
 
 
X 
 
Completion of survey by 
anesthesiologist 
 
 
X 
 
Completion of survey by 
attending surgeon 
 
 
X 
 
Completion of survey by 
subject 
 
 
 
X 


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Assessment of possible AEs 
and/or SAEs 
 
 
X 
X 
 
 
 
 
 
 
 
15.2 Schematic of Study Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain Informed consent. Screen study participants by 
inclusion/exclusion criteria listed in section 7.1 and 7.2. 
Perform enrollment/randomization assessment 
Randomization 
Oral triazolam with placebo 
to match IV midazolam 
Oral placebo to match 
triazolam with IV midazolam 
Preoperative clearance 
Dispensing and administration of 
study drug medication 
Completion of surgical procedure 
Completion of satisfaction survey by 
masked anesthesiologist/CRNA and 
masked surgeon 


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15.3 Case Report Forms (CRF) 
15.3.1 Screening and Consent CRF (Sample) 
 
SCREENING AND CONSENT CHECKLIST 
 Review inclusion/exclusion criteria eligibility 
 Sign consent form 
 Administer delirium questionnaire for subject over 70 years of age or older 
 Confirm eligibility based on delirium questionnaire results (if required)  
 Collection of demographic information 
 Collection medical/ophthalmic history 
 Schedule pre-operative clearance 
 Schedule surgical procedure 
 Discharge with surgical procedure instructions 
 
 
Completion of satisfaction survey by 
participant 


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ELIGIBILITY CRITERIA REVIEW 
INCLUSION CRITERIA 
Must be "yes" 
Yes No 
Notes 
1. Age 18 years or older 
 
 
 
2. Ability to speak and read in English or Spanish 
or Haitian Creole 
 
  
3. Subjects able to consent for themselves 
 
  
4. Outpatient surgical plan for any of the following 
procedures: 
 
Cataract Surgery 
o Cataracts 
 
Retina 
o Pars plana vitrectomy (PPV) 
o PPV with cataracts, epiretinal membrane 
peel, pars plana lensectomy and/or 
endolaser 
o Silicone oil removal 
 
Cornea 
o DSEK 
o Cataracts with DSEK  
o DMEK 
o Cataracts with DMEK 
o Conjunctival and/or corneal lesion 
excisions  
o Pterygium 
 
Glaucoma 
o Ahmed valve 
o Ahmed valve with cataracts 
o Trabeculectomy 
o Trabeculectomy with cataracts 
o Baerveldt 
o Baerveldt with cataracts 
o Endocyclophotocoagulation 
o Endocyclophotocoagulation with cataracts 
o Istent 
o Istent with cataracts 
o Kahook 
o Kahook with cataracts 
o Cypass 
o Cypass with cataracts 
 
 
Category: 
 cataracts 
  
 retina 
  
 cornea 
  
 glaucoma 
 
 
 
 
 
Name of Procedure: _____________ 
______________________________ 
______________________________ 
 


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EXCLUSION CRITERIA 
Must be "no" 
Yes 
No 
N/A at 
this 
time 
Notes 
1. Surgical plan which includes general anesthesia 
 
 
 
 
2. Hypersensitivity or allergy to benzodiazepines 
 
 
 
 
3. Women who are pregnant, have a positive pregnancy test on the day 
of surgery, refuse a pregnancy test, or are nursing 
 
 
 
 
4. Previous delirium after anesthesia with a benzodiazepine 
 
 
 
 
5. Subject is 70 years of age or older and failed the delirium pre-
screening questionnaire 
 
 
 
 
6. Currently experiencing the effects of drugs/alcohol 
 
 
 
 
7. Current oral/IV regimen of any medication inhibiting cytochrome 
P450 3A which includes ketoconazole, itraconazole, nefazodone, 
ritonavir, indinavir, nelavir, saquinavir, and lopinavir 
 
 
 
 
8. Subjects already enrolled in this study for the fellow eye 
 
 
 
 
9. Subjects enrolled in a clinical trial with an investigational drug 
within the past 3 months 
 
 
 
 
10. Failed anesthesia clearance to receive a benzodiazepine 
 
 
 
 
This subject is: 
 
      Eligible for participation               Ineligible for participation 
Signed by study team member who is (1) qualified to assess eligibility and (2) delegated this 
study task by the PI 
 
Signature: 
 
Date:  
 
 
Printed Name: 
  
 
 


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INFORMED CONSENT 
Confirm all of the following Occurred During 
the Consent Process 
Yes 
No 
Notes 
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. 
 
 
 
The consent form was signed and dated by a 
designated member of the study team. 
 
 
 
The consent process was completed prior to the 
start of research procedures. 
 
 
 
Date and time informed consent form signed:  
 
Date: ________________  
Time (24 hour clock): ___ ___ : ___ ___ 
 
Version of ICF signed (e.g., V1, V2) 
 
Was subject given a copy of the signed consent 
form with contact information? 
 Yes  
 No – add comment below 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 


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DELIRIUM QUESTIONNAIRE SCORING 
For each question select the response(s) as it pertains to each question. For each response(s) follow the table across 
to determine the point equivalent. Total each section point equivalents at the bottom of the table. On page 8 enter 
each section point equivalents and add them together, giving you the final delirium pre-screening questionnaire 
score to determine eligibility. All scores from 0-9 will be ELIGIBLE for participation. All scores of 10 or greater 
will be INELIGIBLE for participation.  
 
 N/A Patient is < 70 years of age, delirium questionnaire and corresponding score sheet does not need 
to be completed 
 
Subject Responses Scoring Sheet Part 1 
Question 
Response 
Point Equivalent 
1. Have you ever experienced delirium after 
surgery or a procedure?  
 
 a. Yes 
 10 points 
 b. No 
 0 points 
Part 1 Point Total 
Select only one 
 0 points 
 10 points 
Subject Responses Scoring Sheet Part 2 
Question 
Response 
Point Equivalent 
2. Have you ever been diagnosed with dementia? 
 a. Yes 
 b. No 
 6 points 
 0 points 
3. Have you ever been diagnosed with any of the 
following? Check all that apply. 
If this was not answered, write “N/A”. 
 a. Depression 
 1 point 
 b. Liver failure 
 1 point 
 c. Hypotension 
 1 point 
 d. Stroke 
 1 point 
 e. Alcoholism/substance 
abuse 
 1 point 
 f. Kidney failure 
 1 point 
4. Are you able to complete you daily activities 
independently? 
If this was not answered, write “N/A”. 
 a. Yes 
 0 points 
 b. No 
 1 points 
5. Are you able to get everywhere you need to by 
yourself during the day? 
If this was not answered, write “N/A”. 
 a. Yes 
 0 points 
 b. No 
 1 points 
Part 2 Point Total 
Select only one response or select 0 points if no 
questions were answered in this section 
 0 points 
 1 point 
 2 points 
 3 points 
 4 points 
 5 points 
 6 points 
 7 points 
 8 points 
 9 points 
 10 points 
 11 points 
 12 points 
 13 points 
 14 points 
 


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Research Staff Scoring Sheet 
Question 
Response 
Point Equivalent 
1. Does the patient take 
any of the following 
medication? 
If patient does not take any 
medications, please mark 
“0 points” 
 Opioids (1-2 medications selected) 
 
 1 point 
 Opioids (3 or more medications 
selected) 
 
 6 points 
 Anticonvulsants (1-2 medications 
selected) 
 
 1 point 
 Anticonvulsants (3 or more 
medications selected) 
 6 points 
 Benzodiazepines (1-2 medications 
selected) 
 
 1 point 
 Benzodiazepines (3 or more 
medications selected) 
 
 6 points 
 Anticholinergics (1-2 medications 
selected) 
 
 1 point 
 Anticholinergics (3 or more 
medications selected) 
 
 6 points 
 Antipsychotics (1-2 medications 
selected) 
 
 1 point 
 Antipsychotics (3 or more 
medications) 
 
 6 points 
 
Point Total 
Select only one response or select 0 points if 
no questions were answered in this section 
 0 points 
 1   
 6   
 11  
 16  
 21  
 26 
 2   
 7   
 12  
 17  
 22  
 27 
 3   
 8   
 13  
 18  
 23  
 28 
 4   
 9   
 14  
 19  
 24  
 29 
 5   
 10 
 15  
 20  
 25  
 30 
 
 
 
 
 
 
 
 


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Eligibility Assessment Scoring Sheet 
Section 
Point Total 
Subject Part 1 Response Total 
Enter Response from page 5 
 
Subject Part 2 Response Total 
Enter Response from page 5 
 
Doctor Response Total 
Enter Response from page 6 
 
Overall Delirium Questionnaire Total 
Total of all three sections listed above 
 
Eligibility Assessment 
 Score of 0-9  Patient is 
ELIGIBLE for study. 
 
 Score of 10+  Patient is 
INELIGIBLE for study.  
 
This subject is: 
 
      Eligible for participation     
      Ineligible for participation 
Signed by study team member who is (1) qualified to assess eligibility and (2) delegated 
this study task by the PI 
 
Signature: 
 
Date: ____/____/________ 
 
 
Printed Name:  
 
 
 
 
 
 
 
 
 


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DEMOGRAPHIC INFORMATION 
Date of Birth: 
 
Age (18 years or 
older):  
 
 
Sex: 
 
 Male 
 Female 
 Unknown 
 Undifferentiated 
 
If female, is subject of child bearing potential? 
 Yes 
 No 
Is the subject of 
Hispanic/Latino 
descent? 
 Hispanic or Latino 
 Not Hispanic or Latino 
 Not reported 
 Unknown 
 
Race (check all 
that apply): 
 American Indian or Alaskan Native 
 Asian 
 Black or African American 
 Native Hawaiian or Other Pacific Islander 
 White 
 Declined/ Not Available 
 Other: _____________________________ 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: ____________________ 
 
 
 
 
 
 
 
 
 
 
 
 


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PATIENT VITALS 
Measured? 
 Measured  Complete Table A. 
 Not measured  Complete Table B. 
Table A  
Patient Vitals were Measured 
Date vitals were taken: 
Date: __________________________________ 
Height 
__________ feet __________ inches 
Weight 
__________ lbs. 
BMI 
 
Do vitals need to be re-measured? 
Vitals must be re-measured if they were not measured 
when consented in clinic, at an in-person pre-
operative appointment, or at another appointment 
within the past month 
 Yes, they will be re-measured at: 
 Pre-operative appointment 
 On the day of surgery 
 Other: ________________________ 
 No  Vitals can be used for medication dosing 
Table B 
Patient Vitals were Not Measured 
When will vitals be measured?  
 At a pre-operative appointment 
 On the day of surgery 
 Other: ________________________ 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 


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MEDICAL/OPHTHALMIC HISTORY 
Has the subject experienced any previous 
illnesses, or surgeries, or is the subject 
currently experiencing any illnesses, allergies, 
or chronic conditions or diseases? 
 Yes  Complete the medical and ophthalmic 
condition tables below. 
 No  Form is complete. 
Systemic hypertension 
 Yes  Add to table below. 
 No 
 
Diabetes mellitus 
 Yes  Add to table below. 
 No 
 
Hyperlipidemia 
 Yes  Add to table below. 
 No 
 
Tobacco use 
 Yes  Add to table below. 
 No 
 
Asthma/Bronchitis/COPD 
 Yes  Add to table below. 
 No 
 
Hypercholesterolemia 
 Yes  Add to table below. 
 No 
 
Heart disease 
 Yes  Add to table below. 
 No 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: ____________________ 
 
 
 
 
 
 


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MEDICAL CONDITIONS 
Medical Condition/Event 
Onset Date 
Ongoing or Resolved 
End/Resolution Date 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: ____________________ 
 
 
 
 


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OPHTHALMIC CONDITIONS 
Ophthalmic Condition/Event 
Onset Date 
Ongoing or Resolved 
End/Resolution Date 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
 
 
 Ongoing 
 Resolved 
 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: ____________________ 
 
 
 
 


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SCHEDULE OF PRE-OPERATIVE CLEARANCE 
Date of pre-operative clearance:  
If not scheduled yet, write “will be scheduled” 
 
Date: __________________________________ 
Type of surgical pre-operative clearance 
 Over the phone 
 In-person 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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SCHEDULE OF SURGICAL PROCEDURE 
Date of surgical procedure:  
If not scheduled yet, write “will be 
scheduled” 
 
Date: _____________________________________ 
Name of surgical procedure: 
Category: 
 retina 
  
 cataract 
  
 glaucoma 
  
 cornea 
 
Name of Procedure: 
__________________________________ 
 
__________________________________________ 
Name of attending ophthalmic surgeon: 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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15.3.2 Pre-Procedure and Randomization CRF (Sample) 
 
PRE-PROCEDURE AND RANDOMIZATION CHECKLIST  
 Review inclusion/exclusion criteria eligibility 
 Randomize 
 Confirm pre-operative clearance 
 Confirm date of surgical procedure 
 Coordinate with investigational pharmacy services for medication  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ELIGIBILITY CRITERIA REVIEW 
INCLUSION CRITERIA 
Must be "yes" 
Yes No 
Notes 
1. Age 18 years or older 
 
 
 
2. Ability to speak and read in English or Spanish 
or Haitian Creole 
 
  
3. Subjects able to consent for themselves 
 
  
4. Outpatient surgical plan for any of the following 
procedures: 
 
Cataract Surgery 
o Cataracts 
 
Retina 
o Pars plana vitrectomy (PPV) 
o PPV with cataracts, epiretinal membrane 
peel, pars plana lensectomy and/or 
endolaser 
o Silicone oil removal 
 
Cornea 
o DSEK 
o Cataracts with DSEK  
o DMEK 
o Cataracts with DMEK 
o Conjunctival and/or corneal lesion 
excisions  
o Pterygium 
 
Glaucoma 
o Ahmed valve 
o Ahmed valve with cataracts 
o Trabeculectomy 
o Trabeculectomy with cataracts 
o Baerveldt 
o Baerveldt with cataracts 
o Endocyclophotocoagulation 
o Endocyclophotocoagulation with cataracts 
o Istent 
o Istent with cataracts 
o Kahook 
o Kahook with cataracts 
o Cypass 
o Cypass with cataracts 
 
 
 
Category: 
 cataracts 
  
 retina 
  
 cornea 
  
 glaucoma 
 
 
 
 
 
Name of Procedure: _____________ 
______________________________ 
______________________________ 
 


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EXCLUSION CRITERIA 
Must be "no" 
Yes 
No 
N/A at 
this 
time 
Notes 
1. Surgical plan which includes general anesthesia 
 
 
 
 
2. Hypersensitivity or allergy to benzodiazepines 
 
 
 
 
3. Women who are pregnant, have a positive pregnancy test on the day 
of surgery, refuse a pregnancy test, or are nursing 
 
 
 
 
4. Previous delirium after anesthesia with a benzodiazepine 
 
 
 
 
5. Subject is 70 years of age or older and failed the delirium pre-
screening questionnaire 
 
 
 
 
6. Currently experiencing the effects of drugs/alcohol 
 
 
 
 
7. Current oral/IV regimen of any medication inhibiting cytochrome 
P450 3A which includes ketoconazole, itraconazole, nefazodone, 
ritonavir, indinavir, nelavir, saquinavir, and lopinavir 
 
 
 
 
8. Subjects already enrolled in this study for the fellow eye 
 
 
 
 
9. Subjects enrolled in a clinical trial with an investigational drug 
within the past 3 months 
 
 
 
 
10. Failed anesthesia clearance to receive a benzodiazepine 
 
 
 
 
This subject is: 
 
      Eligible for participation               Ineligible for participation 
Signed by study team member who is (1) qualified to assess eligibility and (2) delegated this 
study task by the PI 
 
Signature: 
 
Date:  
 
 
Printed Name: 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PATIENT VITALS 
Measured? 
 Measured previously  Complete Table A. 
 Not measured  Complete Table B. 
 Re-measured  Complete Table C. 
Table A  
Patient Vitals were Measured Previously 
Date vitals were taken: 
Date: __________________________________ 
Height 
__________ feet __________ inches 
Weight 
__________ lbs. 
BMI 
 
Do vitals need to be re-measured? 
Vitals must be re-measured if they were not measured 
when consented in clinic, at an in-person pre-
operative appointment, or at another appointment 
within the past month 
 Yes, they will be re-measured at: 
 Pre-operative appointment 
 On the day of surgery 
 Other: ________________________ 
 No  Vitals can be used for medication dosing 
Table B 
Patient Vitals were Not Measured 
When will vitals be measured?  
 At a pre-operative appointment 
 On the day of surgery 
 Other: ________________________ 
Table C  
Patient Vitals were Re-measured 
Date vitals were taken: 
Date: __________________________________ 
Height 
__________ feet __________ inches 
Weight 
__________ lbs. 
BMI 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
RANDOMIZATION 


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Was the subject randomized according to their study ID? 
 
 
 YES  Fill out table below.  
 NO  Add comment below.  
Randomization ID: 
Date of 
Randomization 
Name of Medication 
 
Route 
Sedation Dosage 
 
 
Triazolam or placebo 
Microcrystalline cellulose 
Oral 
 
 1 pill – BMI < 35 
 2 pills – BMI ≥ 35 
 
 
 
 
Midazolam or placebo 
Sodium Chloride 0.9% 
IV 
 1 unit dose – BMI < 35 
 2 unit doses – BMI ≥ 35 
 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 


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PRE-OPERATIVE CLEARANCE 
Completed? 
 Complete  Complete Table A. 
 Incomplete  Complete Table B. 
 
Table A  
Pre-Operative Clearance was Completed 
Date of completed pre-operative clearance:  
 
Date: __________________________________ 
Date of pre-operative clearance expiration:  
 
Date: __________________________________ 
Type of surgical pre-operative clearance 
 Over the phone 
 In-person 
 
Table B 
Pre-Operative Clearance was Not Completed 
Date of rescheduled pre-operative clearance:  
 
Date: __________________________________ 
Type of surgical pre-operative clearance 
 Over the phone 
 In-person 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 


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SURGICAL PROCEDURE DETAILS 
Date of surgical procedure:  
Date: _____________________________________ 
Name of surgical procedure: 
Category: 
 cataract 
   
 retina 
   
 cornea 
   
 glaucoma 
 
Name of Procedure: 
__________________________________ 
 
__________________________________________ 
Name of attending ophthalmic surgeon: 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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COORDINATION WITH INVESTIGATIONAL PHARMACY SERVICES 
Tasks to be Completed 
Yes 
No 
If “no”, write a 
comment 
Comments 
1. Send calendar invite to IPS with surgical 
date 
 
 
 
2. Send pharmacy signed consent form page 
 
 
 
3. Send pharmacy EPIC order 
 
 
 
4. Send pharmacy documentation of 
randomization 
 
 
 
Comments: 
___________________________________________________________________________________ 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
15.3.3 Day of Surgical Procedure CRF (Sample) 
 


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DAY OF SURGICAL PROCEDURE CHECKLIST 
 Re-consent under current informed consent form (if required) 
 Administer pregnancy test (if female of childbearing potential)  
 Review inclusion/exclusion criteria eligibility 
 Confirm if pre-operative clearance 
 Obtain medication from IPS 
 Administer medication 
 Complete Anesthesiologist/CRNA Survey  
 Complete Attending Surgeon Survey 
 Document additional anesthesia measures  
 Documentation of anesthesia intraoperative complications 
 Documentation of ocular intraoperative complications 
 Document of completed surgical procedure 
 Assess of possible AEs and/or SAEs 
 Discharge with post-operative day 1 appointment 
 
 
 


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INFORMED CONSENT 
Was the subject re-consented to current 
version?  
 Yes 
 
Version: _________________________________ 
 
Date: ________________  
Time (24 hour clock): ___ ___ : ___ ___ 
 
Was subject given a copy of the signed consent 
form with contact information? 
 Yes  
 No  Add comment below. 
 
 No 
 
 N/A – Subject is already consented under current 
version. 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PREGNANCY TEST ADMINISTRATION 
PREGNANCY TEST ADMINISTRATION 
Sex of Patient:  
 Male  Form is complete. 
 Female  Continue to next question. 
Is the patient of childbearing potential? 
 YES  Continue to next question. 
 NO  Form is complete.  
 
Time of administration: ___ ___ : ___  ___ (24 hour clock) 
 
Pregnancy Test Results: 
 Positive  Patient is INELIGIBLE for study. 
 Negative  Patient is ELIGIBLE for study.  
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ELIGIBILITY CRITERIA REVIEW 
INCLUSION CRITERIA 
Must be "yes" 
Yes No 
Notes 
1. Age 18 years or older 
 
 
 
2. Ability to speak and read in English or Spanish 
or Haitian Creole 
 
  
3. Subjects able to consent for themselves 
 
  
4. Outpatient surgical plan for any of the following 
procedures: 
 
Cataract Surgery 
o Cataracts 
 
Retina 
o Pars plana vitrectomy (PPV) 
o PPV with cataracts, epiretinal membrane 
peel, pars plana lensectomy and/or 
endolaser 
o Silicone oil removal 
 
Cornea 
o DSEK 
o Cataracts with DSEK  
o DMEK 
o Cataracts with DMEK 
o Conjunctival and/or corneal lesion 
excisions  
o Pterygium 
 
Glaucoma 
o Ahmed valve 
o Ahmed valve with cataracts 
o Trabeculectomy 
o Trabeculectomy with cataracts 
o Baerveldt 
o Baerveldt with cataracts 
o Endocyclophotocoagulation 
o Endocyclophotocoagulation with cataracts 
o Istent 
o Istent with cataracts 
o Kahook 
o Kahook with cataracts 
o Cypass 
o Cypass with cataracts 
 
 
 
Category: 
 cataracts 
  
 retina 
  
 cornea 
  
 glaucoma 
 
 
 
 
 
Name of Procedure: _____________ 
______________________________ 
______________________________ 
 


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EXCLUSION CRITERIA 
Must be "no" 
Yes 
No 
N/A at 
this 
time 
Notes 
1. Surgical plan which includes general anesthesia 
 
 
 
 
2. Hypersensitivity or allergy to benzodiazepines 
 
 
 
 
3. Women who are pregnant, have a positive pregnancy test on the day 
of surgery, refuse a pregnancy test, or are nursing 
 
 
 
 
4. Previous delirium after anesthesia with a benzodiazepine 
 
 
 
 
5. Subject is 70 years of age or older and failed the delirium pre-
screening questionnaire 
 
 
 
 
6. Currently experiencing the effects of drugs/alcohol 
 
 
 
 
7. Current oral/IV regimen of any medication inhibiting cytochrome 
P450 3A which includes ketoconazole, itraconazole, nefazodone, 
ritonavir, indinavir, nelavir, saquinavir, and lopinavir 
 
 
 
 
8. Subjects already enrolled in this study for the fellow eye 
 
 
 
 
9. Subjects enrolled in a clinical trial with an investigational drug 
within the past 3 months 
 
 
 
 
10. Failed anesthesia clearance to receive a benzodiazepine 
 
 
 
 
This subject is: 
 
      Eligible for participation               Ineligible for participation 
Signed by study team member who is (1) qualified to assess eligibility and (2) delegated this 
study task by the PI 
 
Signature: 
 
Date:  
 
 
Printed Name: 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PRE-OPERATIVE CLEARANCE CONFIRMATION 
Completed? 
 Complete – complete table A 
 Incomplete – complete table B 
 
Table A  
Pre-Operative Clearance was Completed 
Date of completed pre-operative clearance:  
 
 
Date of pre-operative clearance expiration:  
 
 
Table B 
Pre-Operative Clearance was Not Completed 
Will the surgery be re-scheduled?  
 Yes – re-complete “Before Surgery” forms 
 No – subject will be dropped from the study 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PATIENT VITALS 
Measured? 
  Measured previously  Complete Table A. 
  Re-measured  Complete Table B 
  Not measured  Write comment below 
Table A  
Patient Vitals were Measured Previously 
Date vitals were taken: 
Date: __________________________________ 
Height 
__________ feet __________ inches 
Weight 
__________ lbs. 
BMI 
 
Do vitals need to be re-measured? 
Vitals must be re-measured if they were not measured 
when consented in clinic, at an in-person pre-
operative appointment, or at another appointment 
within the past month 
 Yes  Complete table B  
 No  Vitals can be used for medication dosing 
Table B 
Patient Vitals were Re-measured 
Date vitals were taken: 
Date: __________________________________ 
Height 
__________ feet __________ inches 
Weight 
__________ lbs. 
BMI 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 


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MEDICATION DISPENSING  
Tasks to be Completed 
Yes 
No 
If “no”, write a 
comment 
Comments 
1. Send calendar invite to IPS with surgical 
date 
 
 
 
2. Send pharmacy signed consent form page 
 
 
 
3. Send pharmacy EPIC order 
 
 
 
4. Send pharmacy confirmation of 
randomization  
 
 
 
5. Confirm randomized medication dose 
 
 
 
Comments: 
___________________________________________________________________________________ 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 


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MEDICATION ADMINISTRATION  
Were the randomized medications administered to the 
subject? 
 
 
 YES  Fill out table below.  
 NO  Add comment below.  
Randomization ID: 
If any non-study specific anesthetic interventions taken during pre-operative care, the procedure, 
and/or post-operative care, please document appropriately below. 
Time Administered 
24-hour clock 
Name of Medication 
 
Route 
Sedation Dosage 
 
___ ___ : ___ ___ 
 
Triazolam or placebo 
Microcrystalline cellulose 
Oral 
 
 1 pill – BMI < 35 
 2 pills – BMI ≥ 35 
 
 
___ ___ : ___ ___ 
 
Midazolam or placebo 
Sodium Chloride 0.9% 
IV 
 1 unit dose – BMI < 35 
 2 unit doses – BMI ≥ 35 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 


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SURGICAL PROCEDURE DETAILS 
Date and time surgical procedure start:  
 
Date: ________________  
Time (24 hour clock): ___ ___ : ___ ___  
 
Date and time surgical procedure end:  
 
Date: ________________  
Time (24 hour clock): ___ ___ : ___ ___  
 
Name of completed surgical procedure: 
Category: 
 cataracts 
   
 retina 
   
 cornea 
   
 glaucoma 
 
Name of Procedure: 
__________________________________ 
 
__________________________________________ 
Type of Local Anesthesia Used 
 Topical 
 Subconjunctival 
 Subtenon’s 
 Retrobulbar or peribulbar 
 Other: 
Name of attending ophthalmic surgeon: 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 


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ADDITIONAL ANESTHESIA INTERVENTIONS 
Were additional anesthesia interventions utilized (e.g., 
administration of medications other than the study 
medication) during the procedure? 
 
 
 YES  Fill out table below.  
 NO  Form is complete.  
If any non-study specific anesthetic interventions taken during pre-operative care, the procedure, and/or post-
operative care, please document appropriately below. 
Time Administered 
24-hour clock 
Name of 
Medication 
Route 
Dosage 
Reason for administration 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
 mg 
 mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
 
___ ___ : ___ ___ 
 
 
  Oral  
  IV 
  mg 
  mL 
 
 
Comments: 
 
_________________________________________________________________________________ 
_________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 


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ANESTHESIA INTRAOPERATIVE COMPLICATIONS 
Complication 
Yes 
No 
Comments 
Respiratory obstruction 
 
 
 
Hypercapnia 
 
 
 
Hypocapnia 
 
 
 
Hypoventilation 
 
 
 
Hypoxemia 
 
 
 
Hypertension 
 
 
 
Hypotension 
 
 
 
Cardiac arrhythmias 
 
 
 
Hypothermia 
 
 
 
Hyperthermia 
 
 
 
Itching 
 
 
 
Anaphylaxis 
 
 
 
Other: 
__________________________________ 
 
 
 
Comments: 
___________________________________________________________________________________ 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 


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OCULAR INTRAOPERATIVE COMPLICATIONS 
Complication 
Yes 
No 
Comments 
Corneal burn 
 
 
 
Descemet Detachment 
 
 
 
Hyphema 
 
 
 
Iris prolapse 
 
 
 
Floppy iris syndrome 
 
 
 
Iridodialysis 
 
 
 
Dropped nucleus 
 
 
 
Retained lens fragment 
 
 
 
Anterior capsule tear 
 
 
 
Posterior capsule tear 
 
 
 
Aqueous misdirection 
 
 
 
Suprachoroidal hemorrhage 
 
 
 
Other: 
__________________________________ 
 
 
 
Comments: 
___________________________________________________________________________________ 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 


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ANESTHESIOLOGIST/CRNA SURVEY SCORING 
Anesthesiologist/CRNA Responses Scoring Sheet Part 1 
Question 
Response 
Point Equivalent 
1. The patient’s pain level was well controlled 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
2. The patient’s anxiety level was well controlled 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
3. Intravenous (IV) medication was required for 
breakthrough pain during surgery 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
4. There was no undesired movement 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
5. The patient was cooperative 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 


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Anesthesiologist/CRNA Responses Scoring Sheet Part 2 
Question 
Response 
Point Equivalent 
6. There was no operative deviation or 
complication as a result of the patients initial 
anesthesia medication 
a. Type of complication/deviation (if any): 
_____________________________ 
_____________________________ 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
 
Final Anesthesiologist/CRNA Satisfaction Survey Score Determination 
Question Number 
Point(s) 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
Final Anesthesiologist Satisfaction Score 
Average points for questions 1-6 
  
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 


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ATTENDING OPHTHALMOLOGIST SURGEON SURVEY SCORING 
Surgeon Responses Scoring Sheet Part 1 
Question 
Response 
Point Equivalent 
1. I was satisfied with the anesthesia administered 
during surgery 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
2. The patient’s pain level was well controlled 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
3. The patient’s anxiety level was well controlled 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
4. There was no undesired movement 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
5. The patient was cooperative 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 


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Surgeon Responses Scoring Sheet Part 2 
Question 
Response 
Point Equivalent 
6. There was no deviation from the operative 
standard that occurred as a result of the 
patient’s initial anesthesia medication 
a. Type of complication/deviation (if any): 
___________________________ 
___________________________ 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
7. Did you need to request additional pain 
medications from the anesthesiologist? 
 Yes 
Non-scoring 
 No 
 
Final Surgeon Satisfaction Survey Score Determination 
Question Number 
Point(s) 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
Final Surgeon Satisfaction Score 
Average points for questions 1-6 
  
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 


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ADVERSE EVENT(S) ASSESSMENT 
Were any adverse events experienced? 
 
 
 YES  Fill out table below.  
 NO  Form is complete.  
If any adverse events took place during pre-operative care, the procedure, and/or post-operative care, 
please document below, add to the adverse event log, and appropriate reports. 
Time of Event 
24-hour clock 
Name of Event 
Notes 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 


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DAY OF SURGICAL PROCEDURE DISCHARGE AND NEXT VISIT 
Discharge Instructions – Scheduled Next Visit (+2 days from Surgical Procedure)  
 Instruct subject to contact site immediately if extreme pain, nausea, vomiting, or shortness of breath 
is experienced. 
 Discharge with emergency contact instructions. 
 Discharge with instructions for post-operative day 1 visit. 
What is the date/time agreed with 
the subject for returning for the 
post-operative day 1 visit? 
Date: __________________ 
Time: ___ ___ : ___ ___ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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15.3.4 Post-Operative Day 1 CRF (Sample) 
 
POST-OPERATIVE DAY 1 CHECKLIST 
 Re-consent under current informed consent form (if required) 
 Complete patient satisfaction survey 
 Assessment of possible AEs and/or SAEs 
 Dispense $25 ClinCard to reimburse for travel expenses 
 Send home with follow-up instructions 
 
 
 


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INFORMED CONSENT 
Was the subject re-consented to current 
version?  
 Yes 
 
Version: _________________________________ 
 
Date: ________________  
Time (24 hour clock): ___ ___ : ___ ___ 
 
Was subject given a copy of the signed consent 
form with contact information? 
 Yes  
 No  Add comment below. 
 
 No 
 
 N/A – Subject is already consented under current 
version. 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PATIENT SATISFACTION SURVEY SCORING 
Subject Responses Scoring Sheet Part 1 
Question 
Response 
Point Equivalent 
1. I hurt during my surgery 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
2. I felt good during surgery 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
3. I felt pain during surgery 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
4. I was satisfied with the anesthesia care 
during surgery 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
 
 
 
 
 
 
 


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Subject Responses Scoring Sheet Part 2 
Question 
Response 
Point Equivalent 
5. I itched during surgery 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
6. I felt relaxed during surgery 
 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
7. I felt safe during surgery 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
8. I threw up after surgery 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
9. I felt like throwing up after surgery 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
 


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Subject Responses Scoring Sheet Part 3 
Question 
Response 
Point Equivalent 
10. I would have the same anesthetic again 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
11. I was too hot or too cold during surgery 
 
 Disagree very 
much 
 6 point 
 Disagree  
 5 points 
 Disagree a little 
 4 points 
 Agree a little 
 3 points 
 Agree  
 2 points 
 Agree very much 
 1 points 
12. My pain level was as expected and well 
controlled during surgery 
 Disagree very 
much 
 1 point 
 Disagree  
 2 points 
 Disagree a little 
 3 points 
 Agree a little 
 4 points 
 Agree  
 5 points 
 Agree very much 
 6 points 
13. During your operation, your 
anesthesiologist gave you a medication to 
make you feel more calm, relaxed and/or 
sleepy. If you were to have this type of 
surgery again, would you prefer: 
 More medicine 
Non-scoring 
 Same medicine 
 Less medicine 
 No medicine 
 
 
 
 
 
 
 
 
 
 


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Final Patient Satisfaction Survey Score Determination 
Question Number 
Point(s) 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
11 
 
12 
 
Final Patient Satisfaction Score 
Average points for questions 1-12 
  
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 
 


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ADVERSE EVENT(S) ASSESSMENT 
Were any adverse events experienced? 
 
 
 YES  Fill out table below.  
 NO  Form is complete.  
If any adverse events took place since discharge from the hospital, please document below, add to the 
adverse event log, and appropriate reports. 
Date of Event 
Time of Event 
(If available) 
24-hour clock 
Brief Description of Event 
Notes 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
 
 
___ ___ : ___ ___ 
 
 
 
Comments: 
 
___________________________________________________________________________________ 
 
___________________________________________________________________________________ 
Signature of person completing above fields 
 
Signature: ________________________________________  Date: _________________________ 
 
 


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STUDY COMPLETION AND DISCHARGE 
Discharge Instructions – Scheduled Post-Operative Visits 
 Instruct subject to contact site immediately if extreme pain, nausea, vomiting, or shortness of breath 
is experienced. 
 Discharge with emergency contact instructions. 
 Discharge with instructions for post-operative week 1 and month 1 visit. 
 Dispense $25 ClinCard to reimburse of travel expenses 
What is the date/time agreed 
with the subject for returning 
for post-operative week 1 visit? 
Date: __________________ 
Time: ___ ___ : ___ ___ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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15.4 Midazolam Package Insert 
 


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15.5 Triazolam Package Insert 


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15.6 Delirium Questionnaire (Sample)  
  
Instructions to the patient: Please answer all of the questions independently to the best of your ability. 
 
1. Have you ever experienced delirium after surgery or a procedure? 
 Yes 
 No 
 
 
If you answered question 1 as “yes”, you have completed this questionnaire. Otherwise, continue to 
question 2. 
 
2. Have you ever been diagnosed with dementia?  
 Yes 
 No 
 
3. Have you ever been diagnosed with any of the following? If so, please check all that apply. 
Depression 
Liver failure 
Hypotension (Low blood pressure) 
Stroke 
Alcoholism/substance abuse 
 
Kidney failure 
 
4. Are you able to complete you daily activities independently? 
 Yes 
 No 
 
 
5. Are you able to get everywhere you need to by yourself during the day? 
 Yes  
 No 
 
 
 
You have now completed your portion of the questionnaire Thank you for your participation with this 
important research. 
 
 
To be Completed by Research Staff 
 
1. Does the patient take any of the following medications? If so, please list all that apply. 
 
a. Opiods:  
 
 
 
 
 
b. Anticonvulsants: 
 
 
 
 
c. Benzodiazepines: 
 
 
 
 
d. Anticholinergics: 
 
 
 
 
e. Antipsychotics:  
 
 
 
 
 


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15.7 Satisfaction Surveys 
15.7.1 Post-Surgery Anesthesiologist/CRNA Satisfaction Survey (Sample) 
Post-Surgery Anesthesiologist/CRNA Survey 
 
Instructions for the survey: Please select the response you feel best describes the statement based on this subject’s 
surgical procedure.   
 
1.  The patient’s pain level was well controlled  
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
2. The patient’s anxiety level was well controlled 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
3. Intravenous (IV) medication was required for breakthrough pain during surgery 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
4. There was no undesired movement 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
5. The patient was cooperative 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
7. There was no operative deviation or complication as a result of the patients initial anesthesia 
medication 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
 
 
 
Type of complication/deviation (if any):  
 
 
 
 
 
 
Research Staff Use Only: 
           Study ID#: ______________________________________ 
 
Date of surgery: __________________________________ 
 
Ophthalmology surgeon: ___________________________ 
 
Date of survey completion: _________________________ 
 
Name of survey administrator: ______________________ 
 


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15.7.2 Post Surgery Surgeon Satisfaction Survey (Sample) 
Post-Surgery Surgeon Survey 
 
Instructions for the survey: Please select the response you feel best describes the statement based on this subject’s 
surgical procedure.   
 
Surgery Group Type (please select one): 
Cataract  
Retina  
Cornea  
Glaucoma 
 
Type of Local Anesthesia (please select one): 
Topical  
Subconjunctival  
Subtenon’s  
Retrobulbar/peribulbar 
 Other 
 
1. I was satisfied with the anesthesia administered during surgery 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
2. The patient’s pain level was well controlled 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
3. The patient’s anxiety level was well controlled 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
4. There was no undesired movement 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
5. The patient was cooperative 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
8. There was no deviation from the operative standard that occurred as a result of the patient’s initial 
anesthesia medication 
□Disagree 
very much 
□Disagree  
□Disagree a 
little 
□Agree a 
little 
□Agree  
□Agree very 
much 
 
Type of complication/deviation (if any): _____________________________________ 
 
7. Did you need to request additional pain medications from the anesthesiologist? 
□ Yes 
□ No 
 
Research Staff Use Only: 
Study ID#: ______________________________________ 
Date of surgery: __________________________________ 
Ophthalmology surgeon: ___________________________ 
Date of survey completion: _________________________ 
Name of survey administrator: ______________________ 


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15.7.3 Post-Surgery Patient Satisfaction Survey (Sample) 
 


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15.8 AE, SAE, and UP Tracking and Reports 
15.8.1 AE, SAE, and UP Report Log (Sample) 
 


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15.8.2 AE, SAE, and UP Review Log (Sample) 
 
 
 
 
 
 
 
 
 
 
 


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15.8.3 SAE and UP Report Form (Sample) 


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15.8.4 Data Safety Monitoring Report (Sample) 
 
 
 


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