The Use of Sugammadex as Rescue Therapy Following Inadequate Reversal With Neostigmine
Phase: PHASE4
Conditions: Neuromuscular Blockade
Sponsor: Emory University

         The use of Sugammadex as rescue therapy following inadequate reversal with neostigmine 
                                                                NCT05661409 
                                                                 10.14.2024
         The use of Sugammadex as rescue therapy following inadequate reversal with neostigmine 
                                                                NCT05661409 
                                                                 10.14.2024

Protocol Title: The use of sugammadex as rescue therapy following inadequate reversal with 
neostigmine 
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IRB Form BIO 01192022
PROTOCOL TITLE:   
The use of sugammadex as rescue therapy following inadequate reversal with neostigmine 
EXTERNAL (NON-EMORY) COLLABORATORS                                                                   
N/A
PRINCIPAL INVESTIGATOR:
Name   Matthew Whalin, MD
Department Anesthesiology, Grady Memorial Hospital
Telephone Number  404-616-5014
Email Address  mwhalin@emory.edu 
CO INVESTIGATOR:
Name David Boorman
Department Anesthesiology, Emory University School of Medicine
Telephone Number 404-712-1939
Email Address david.boorman@emory.edu
VERSION: 3 
STUDY SUPPORTER: 
Georgia CTSA (Clinical & Translational Science Alliance) pilot grants program 
IND EXEMPT
REVISION HISTORY
Revision #
Version 
Date
Summary of Changes
3
10/14/2024
Change in PI

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Table of Contents
1.
Study Summary....................................................................................................................5
2.
Objectives ............................................................................................................................5
3.
Background..........................................................................................................................5
4.
Study Endpoints...................................................................................................................5
5.
Study Intervention/Investigational Agent ...........................................................................6
6.
Procedures Involved ............................................................................................................6
7.
Statistical Analysis Plan........................................................................................................7
8.
Data and/or Specimen Banking ...........................................................................................7
9.
Sharing of Results with Participants ....................................................................................7
10.
Study Timelines....................................................................................................................8
11.
Inclusion and Exclusion Criteria...........................................................................................8
12.
Population ...........................................................................................................................8
13.
Vulnerable Populations .......................................................................................................9
14.
Local Number of Participants ..............................................................................................9
15.
Recruitment Methods........................................................................................................10
16.
Withdrawal of Participants................................................................................................10
17.
Risk to Participants ............................................................................................................11
18.
Potential Benefits to Participants......................................................................................11
19.
Compensation to Participants ...........................................................................................11
20.
Data Management and Confidentiality .............................................................................11
21.
Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity................12
22.
Provisions to Protect the Privacy Interest of Participants .................................................13
23.
Economic Burden to Participants ......................................................................................14
24.
Informed Consent..............................................................................................................14
25.
Setting................................................................................................................................16
26.
Resources Available...........................................................................................................17
27.
Multi-Site Research When Emory is the Lead Site.............................................................17
28.
References.........................................................................................................................18
29.
Protocol Checklist ..............................................................................................................18

Protocol Title: The use of sugammadex as rescue therapy following inadequate reversal with 
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1. Study Summary
Project Title
The use of sugammadex as rescue therapy following 
inadequate reversal with neostigmine
Project Design
Double-blind randomized placebo-controlled dose-
response trial
Primary Objective
To determine what is an appropriate dose of 
sugammadex as rescue therapy following inadequate 
reversal with neostigmine
Secondary Objective(s)
Research 
Intervention(s)/Interactions
2 mg/kg, 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 
mg/kg of sugammadex and placebo
Study Population
-
Aged 18 years and above
-
Scheduled to undergo an elective surgery in 
the main operating room or outpatient surgery 
center at Grady Memorial Hospital,
-
Receive general anesthesia (standardized to 
sevoflurane for maintenance),
-
Receive rocuronium for NMB, 
-
Receive neostigmine for NMB reversal, and 
-
Achieve a TOF count of at least 3 twitches but 
not a TOF ratio of 0.9 fifteen minutes after 
neostigmine has been given. 
Sample Size
36
Study Duration for 
individual participants
1 day (from start of surgery until PACU discharge)
Study Specific 
Abbreviations/ Definitions 
NMB: neuromuscular blockade
PACU: post anesthesia care unit
TOF: train of four
Funding Source (if any)
Georgia CTSA (Clinical & Translational Science 
Alliance) pilot grants program

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2. Objectives
Objective:
To determine what is an appropriate dose of sugammadex as rescue therapy 
following inadequate reversal with neostigmine.
Hypothesis:
That a lower dose of sugammadex than currently recommended by the 
manufacturer is enough to achieve adequate reversal following neostigmine.
3. Background
Neuromuscular blocking agents (NMBAs) are commonly used in the practice of anesthesiology 
for skeletal muscle relaxation to facilitate tracheal intubation, mechanical ventilation, and to 
provide optimal surgical conditions. They fall into two categories, i.e. the non-depolarizing 
agents versus succinylcholine, which is the only depolarizing agent in clinical use. Non-
depolarizing NMBAs in turn are classified as either an aminosteroid or benzylisoquinolinium 
compound; the former include pancuronium, vecuronium, and rocuronium, whereas the latter 
include atracurium, cisatracurium and mivacurium (1). In order to prevent residual NMB, it is 
vital to adequately reverse any use of a non-depolarizing NMBA. This was historically done 
using an anticholinesterase such as neostigmine, which would increase the concentration of 
acetylcholine at the neuromuscular junction leading to the return of neuromuscular 
transmission. 
Unfortunately, there are disadvantages to the use of an anticholinesterase. Firstly, there is a 
“ceiling” effect, i.e. “once the acetylcholinesterase enzyme is maximally inhibited by an 
anticholinesterase agent and peak concentrations of acetylcholine are present, the 
administration of additional drug will not further increase acetylcholine levels or enhance 
recovery of neuromuscular blockade” (2, p. 842). Secondly, the use of an anticholinesterase 
with relatively mild residual blockade may lead to paradoxical muscle weakness. Thirdly, 
anticholinesterase agents have a multitude of adverse effects due to their muscarinic effects 
such as nausea, bradycardia, and bronchospasm. (2) Thus, an alternative method to antagonize 
the non-depolarizing NMBAs came to be a topic of research.
It was in this context that sugammadex was found to be a valuable addition to the 
anesthesiologist’s armamentarium. It is a modified γ-cyclodextrin that encapsulates the 
aminosteroid NMBAs rocuronium and vecuronium. It was first discovered by the Organon 
Laboratories in Scotland and was then known as the agent Org 25969. The successful results of 
the first in vivo study was published in 2002 (3), where rocuronium was reversed in 
anesthetized monkeys, and the first phase I study was published in 2005 (4). It was approved by 
the United States Food and Drugs Administration (FDA) in 2015, with the following three dosing 
ranges, i.e. 2 mg/kg if the train-of-four (TOF) stimulation reaches the second twitch, 4 mg/kg if 
there is no twitch response to TOF stimulation but there are 1 to 2 post-tetanic counts (PTC), 
and 16 mg/kg after administration of 1.2 mg/kg of rocuronium (5). 

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In the clinical assessment of NMBA reversal, a TOF ratio1 of 0.7 was historically seen as 
adequate, but this has been revised in the face of recent evidence that showed a TOF ratio of 
any less than 0.9 could result in “impaired pharyngeal function, airway obstruction, an 
increased risk of aspiration of gastric contents, an impaired hypoxic ventilatory control, and 
unpleasant symptoms of muscle weakness” (2, p. 836). Even if the TOF stimulation count is 4 
but there is still detectable TOF fade, the TOF ratio will equate to 0.1-0.4 (6); this does not 
significantly change with a 5-second, 50-Hz tetanic stimulation (TOF ratio ~0.3) and is only 
slightly improved with double-burst stimulation (TOF ratio ~0.6-0.7) (2).
Carvalho et al. conducted a meta-analysis of 53 studies (12,664 adult patients), where the 
pooled residual NMB incidence ranged from 0.115 when quantitative neuromuscular 
monitoring was used to 0.331 where no neuromuscular monitoring was used (7). Raval et al. 
conducted a meta-analysis of 20 randomized controlled trials (1,923 adult patients), where 
residual NMB (TOF ratio < 0.9) was found in 2.8% of patients who received sugammadex 
compared to 39% of those who received neostigmine 15 minutes post administration for a 
moderate block (TOF count 1-4) compared to 1.1% for sugammadex versus 99.1% for 
neostigmine 15 minutes after administration for a deep block (PTC 1-5) (8). Concerningly, 60 
minutes after administration, 2.1% of the sugammadex group versus 19% of the neostigmine 
group still had NMB in the moderate block group compared to 0.4% of the sugammadex group 
versus 39.3% of the neostigmine group in the deep block group. When expanded to 
observational studies (58 studies with 25,277 adult patients), the incidence of residual NMB 
(TOF ratio < 0.9 upon arrival to PACU) ranged from 0% to 90.5% (median 30%), which was 
significantly lower (0% to 16%) in the sugammadex group compared to 3.5% to 90.5% in the 
neostigmine group and 15% to 89% in the spontaneous recovery group (9).
The incidence of residual NMB in the pediatric population has been variably reported. Ledowski 
et al. published in 2015 a series of 64 children (average age 8.2 years) who received NMBA for 
tracheal intubation, only 33 of whom received NMB reversal (32 with neostigmine 0.08 mg/kg 
and 1 with sugammadex); 19.4% of those who received no reversal and 37.5% of those who 
received neostigmine was found to have residual NMB (TOF ratio < 0.9) prior to extubation 
using acceleromyometry, giving an overall incidence of 28.1% (10). Similarly, Klucka et al. 
published in 2019 a series of 291 children (range: 29 weeks to 19 years of age) who received 
NMBA for surgery, 68 of whom received NMB reversal; the TOF ratio was found to be < 0.9 in 
48.2% of patients prior to extubation in the OR versus 26.9% upon arrival to the PACU using 
accelerometry (11).
A Cochrane systematic review published in 2017 (12) analyzed 41 randomized controlled trials 
of 4,206 adults who received non-depolarizing NMBAs for elective surgery, and found that a 2 
mg/kg dose of sugammadex was 6.6 times faster (10.22 minutes) than a 0.05 mg/kg dose of 
neostigmine in reversing moderate NMB from the second twitch (T2) to a TOF ratio > 0.9, while 
1 The ratio of the fourth (T4) to the first (T1) twitch after a TOF stimulation

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a 4 mg/kg dose of sugammadex was 16.8 times faster (45.78 minutes) than a 0.07 mg/kg dose 
of neostigmine in reversing deep NMB from a PTC 1-5 to TOF ratio > 0.9. 
However, less is known when there is shallow NMB, i.e. when the TOF count is 4 but there is 
still detectable TOF fade. Concerningly, Kirkegaard et al. found in 2002 that the maximal 0.07 
mg/kg dose of neostigmine was unable to reverse all patients to a TOF ratio of 0.9 within 30 
minutes, even at a pre-intervention TOF count of 4 (13). Whether a lower dose of sugammadex 
would be sufficient to achieve a TOF ratio of 0.9 after shallow NMB has been examined by 
Schaller et al. in 2010 and Pongrácz et al. in 2013. The former group found that in a group of 94 
adults undergoing elective surgery, a dose of 0.22 mg/kg of sugammadex was equivalent to a 
dose of 0.034 mg/kg of neostigmine in reversing NMB from a TOF ratio of 0.5 to 0.9 within 5 
minutes in 95% of their patients (14). Conversely, Pongrácz’s group found that a 0.5 mg/kg dose 
of sugammadex reversed NMB from a TOF count of 4 to a TOF ratio of 1.0 in 4.1 minutes on 
average compared to 2.1 minutes for a 1.0 mg/kg dose of sugammadex, 1.8 minutes for a 2.0 
mg/kg of sugammadex, and 8.5 minutes for a 0.05 mg/kg dose of neostigmine (15).
Due to the high cost of sugammadex, some researchers have hypothesized that a lower dose is 
required when combined with neostigmine. A 2015 study from Beirut in adults undergoing 
elective surgery demonstrated that a dose of 2 mg/kg of sugammadex combined with 
neostigmine 0.05 mg/kg was non-inferior to the standard dose of 4 mg/kg of sugammadex in 
reversing deep NMB, defined as returning from a TOF count of 0 to a TOF ratio of 0.9 within 5 
minutes, with similar times to extubation as well as no cases of recurarization in the post 
anesthetic care unit (PACU) (16). Lobaz, Sammut and Damodaran reported in 2013 the use of 
sugammadex as rescue therapy for a 71-year-old patient with end stage renal disease who was 
unable to be weaned off the ventilator almost five hours after receiving a single 1.2 mg/kg dose 
of rocuronium. He had initially achieved a TOF of 4, was reversed with 2.5 mg of neostigmine 45 
minutes after induction, but failed to maintain adequate spontaneous ventilation despite his 
TOF remaining at 4, and was transferred to the intensive care unit 3 hours post induction. 
There, his TOF steadily declined to 2, as a result of which he received a 6 mg/kg dose of 
sugammadex, causing him to be successfully extubated ten minutes later (17). It is similarly 
important to dose sugammadex appropriately; Carollo et al. published a case report in 2019 of 
an 8-month-old patient who had recurarization after a 4 mg/kg dose of sugammadex was given 
with a TOF count of 2/4, which fortunately resolved after a second 4 mg/kg dose of 
sugammadex (18).
Lastly, known common adverse effects of neostigmine include bradycardia, nausea and 
vomiting (19), while the use of sugammadex has been found to lead to nausea, vomiting, 
hypotension and headache in ≥ 10% of patients (5). There have also been case reports of 
marked bradycardia possibly leading to cardiac arrest with the use of both agents.

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4. Study Endpoints
Primary study outcome:
The time taken to achieve a TOF ratio of 0.9 after the use of the intervention drug 
versus placebo in a patient population that has already received neostigmine for NMB 
reversal.
Secondary study outcome:
The percentage of patients who achieve a TOF ratio of 0.9 within 1 minute, 2 minutes, 5 
minutes, and 10 minutes.
Safety outcomes:
The incidence in PACU (measured in %) of:
i.
Nausea,
ii.
Vomiting,
iii.
Bradycardia2,
iv.
Tachycardia3, and
v.
Hypotension4.
For the safety outcomes, patients who were recruited but did not receive the intervention drug 
will be compared to patients who did receive the intervention drug to determine if their rates 
of adverse effects are similar. However, the sample size in this study is too low to perform 
formal non-inferiority tests on this data.
5. Study Intervention/Investigational Agent 
Study intervention:
Patients will be randomized to six groups: 2 mg/kg (the lowest dose approved by 
the FDA), 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and 
placebo (normal saline).
The Grady Memorial Hospital operating room pharmacy will store and dispense the 
study drug, while the anesthesia provider in the operating room will administer it.
As elaborated before, sugammadex is a FDA-approved drug that is in routine clinical use for 
NMB reversal.
2 Heart rate < 60 beats per minute over two or more recordings if not present pre-operatively
3 Heart rate > 100 beats per minute over two or more recordings if not present pre-operatively
4 Systolic blood pressure < 90 mmHg and/or mean arterial pressure < 65 mmHg over two or more recordings

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The study protocol was submitted to the U.S. FDA, and found to be exempt from IND 
regulations (PIND 162798 dated 2022-Jul-13). 
6. Procedures Involved
This project is a double-blind randomized placebo-controlled dose-response trial that aims to 
determine the time taken to achieve adequate reversal comparing five doses of sugammadex 
as rescue therapy following inadequate reversal with neostigmine. 
We will identify patients in the Grady Memorial Hospital OR who are scheduled to undergo an 
elective surgery under general anesthesia, received rocuronium for NMB and neostigmine for 
NMB reversal, and achieved a TOF count of at least 3 twitches but not a TOF ratio of 0.9 fifteen 
minutes after neostigmine has been given.
These patients will be randomized using the Emory University REDCap (Research Electronic 
Data Capture) software to six groups: 2 mg/kg (the lowest dose approved by the FDA), 1 mg/kg, 
0.5 mg/kg, 0.25 mg/kg, 0.125 mg/kg of sugammadex and placebo. Doses would be based on 
actual body weight. The time taken to reach a TOF ratio of 0.9 thereafter would be measured. If 
the patient fails to achieve this goal by 10 minutes, sugammadex would be given in 2 mg/kg 
increments until the patient reaches this threshold and can be safely extubated. The TOF ratio 
would be measured again at 30 minutes after arrival at the PACU to exclude delayed residual 
NMB with the plan to give further 2 mg/kg doses of sugammadex if detected.
The inclusion of a placebo group would allow us to examine if patients may recover 
spontaneously over that time without needing any sugammadex at all, and what parameters 
may predict that subset of patients. It will also improve the dose response modelling, in that 
randomization has been weighted so that patients who are least likely to need sugammadex 
(i.e. if they achieved a TOF count of 4 twitches without fade) are more likely to be in the 
placebo group or at the lowest dose of sugammadex that is being tested.
The time taken to a TOF ratio of 0.9 after the intervention drug has been given would be 
compared for statistically significant differences, controlling for the:
-
TOF count (3 twitches, 4 twitches with fade, 4 twitches without fade), and
-
TOF ratio (0 to < 0.9)
15 minutes after neostigmine has been given and prior to giving the intervention drug.
Quantitative neuromuscular monitoring will be carried out using electromyography, which 
measures the TOF ratio every 20 seconds. The TOF count (between 0 to 4) and the TOF ratio (0 
to 1) would be measured and recorded at baseline and after administration of the study drug. If 
the TOF ratio remains < 0.9 after this, or if the patient exhibits any symptoms or signs of 
residual NMB blockade, a further 2 mg/kg dose of sugammadex would be given until the 
patient achieves a TOF ratio of 0.9.

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7. Statistical Analysis Plan
Power Analysis
An a priori power analysis was conducted using G*Power 3.1.9.4 (20).  We used an ANOVA F-
Test for one-way omnibus difference between groups, alpha threshold of 0.05 for rejecting the 
null hypothesis, statistical power of 0.80 and a "very large" effect size of 0.765 was calculated 
based on results from a 2013 randomized controlled trial that examined time from TOF count = 
4 to TOF ratio 1.0 comparing neostigmine to three different doses of sugammadex: 0.5, 1.0, and 
2.0 mg/kg (15).  This gave a required sample size of N=24.  This number was increased to N=36 
to account for patients with poor modeling from a high starting TOFR (resulting in few data 
points for that patient) or incomplete recovery within the maximum ten minutes allotted.  An 
anticipated 70% of those enrolled will become ineligible because of an initial TOFR of 90% or 
greater, thus not requiring any medications, so up to 120 patients may need to be recruited and 
screened, but only 36 will receive any treatment.
Methodology
Randomization will occur with permuted block randomization, divided into 18 groups, to ensure 
proportional allocation of participants in each group over time.  Dose randomization will be 
assigned after stratifying by initial TOFC, with a set number of patients recruited for each group, 
as seen the table below.  This ensures that patients who likely need a lower dose are more 
likely to receive it. Randomization will not occur until participation is assured, i.e., their TOFR is 
<0.90.  
Table 1: Randomization plan for patients (n=36)
Sugammadex Dose (mg/kg) 
0.00
0.125
0.25
0.50
1.00
2.00
Initial 
TOFR
Initial 
TOFC
Fade
placebo
Total
≥ 0.9
NA
NA
No treatment; track for adverse events
0
No
3 pt
3 pt
2 pt
2 pt
1 pt
1 pt
12
4
Yes
2 pt
2 pt
2 pt
2 pt
2 pt
2 pt
12
< 0.9
3
NA
1 pt
1 pt
2 pt
2 pt
3 pt
3 pt
12
< 0.9
0-2
NA
No treatment; track for adverse events
0
Total # of Patients (pt)
6
6
6
6
6
6
36
Statistical Methodology
Assuming assumptions are valid, an increasing exponential regression model with random 
intercept will be fitted with Time of Four Ratio versus Time, stratified by the natural log of the 
five dose levels (modeled below).  This translates to a slow response initially followed by a more 
rapid response later.  The random intercept will allow for different initial TOFR values.  

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𝑇𝑂𝐹𝑅= 1
𝐵𝑒(𝐴+𝑡𝑖𝑚𝑒) 𝐵+ 𝑇𝑂𝐹𝑅𝑖𝑛𝑖𝑡𝑖𝑎𝑙+ 𝐶∗ln (𝑑𝑜𝑠𝑒)
"Success" will be defined as TOFR of  ≥0.9 within 5 minutes for 95% of patients, following the 
model estimate, adjusting for the 95% confidence intervals of the estimates, based on initial 
TOF ratios, which may be grouped as needed.  A secondary analysis will be conducted by TOFC 
to determine optimal dose at each TOFC level, and if TOFC correlates strongly with TOFR.
8. Data and/or Specimen Banking
N/A
9. Sharing of Results with Participants
N/A
10. Study Timelines
All subjects are anticipated to participate in the study from the start of their surgery to the time 
of their discharge from the PACU, which should be on the same day. It is expected that 1 year 
would be required to enroll all study subjects, and for the study to be completed by July 2023.
11. Inclusion and Exclusion Criteria
Individuals will be screened for eligibility at the anesthesia pre-admission clinic.
Inclusion criteria:
-
Patients aged 18 years and above who will 
-
Undergo an elective surgery in the main operating room or outpatient surgery center at 
Grady Memorial Hospital,
-
Receive general anesthesia (standardized to sevoflurane for maintenance),
-
Receive rocuronium for NMB, 
-
Receive neostigmine for NMB reversal,
-
Achieve a TOF count of at least 3 twitches but not a TOF ratio of 0.9 fifteen minutes 
after neostigmine has been given, and
-
Able and willing to provide informed consent.
Exclusion criteria:

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-
Pregnancy and/or lactating, 
-
BMI ≥ 40, 
-
Severe renal impairment, i.e. chronic kidney disease stages IV and V as defined by GFR < 
30 ml/min/1.73 m2 (21),
-
Severe hepatic impairment, i.e. Child-Pugh score C5 (22, 23),
-
Pre-existing neuromuscular disease, 
-
Anticipated need for postoperative intubation, and/or
-
Known hypersensitivity reactions to rocuronium, neostigmine and/or sugammadex.
12. Population
We will not be including the following special populations:

Adults unable to consent

Individuals under the age of 18 years

Pregnant women

Prisoners

Cognitively impaired or Individuals with Impaired Decision-Making Capacity

Individuals who are not able to clearly understand English
Racial and ethnic classification of subjects would be collected from their electronic medical 
record (which is based on self-identification) for descriptive statistics. Race would comprise the 
following six categories: white, black or African American, American Indian or Alaska Native, 
Asian, Native Hawaiian or Other Pacific Islander, and two or more races. Ethnicity would be 
either Hispanic/Latino or not Hispanic/Latino. This information will not be used as a variable to 
explain differences between participants, but will be presented in Table 1 as part of the study’s 
demographic data, which may help in assessing if the study could be generalized to other 
patient populations in turn.
The number of individuals who are not able to clearly understand English constitute a minority 
of the patient population at Grady Memorial Hospital.
13. Vulnerable Populations
N/A
14. Local Number of Participants
Up to 120 patients may need to be enrolled and screened, but only 36 will receive any 
treatment. We anticipate a similar percentage of participants according to sex, but the majority 
5 Child-Pugh classification includes bilirubin, INR, albumin, ascites and encephalopathy. A total score of 5-6 is class 
A, 7-9 is class B and 10-15 is class C.

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would likely be either white or black due to general patient demographics in Grady Memorial 
Hospital.
15. Recruitment Methods
All patients presenting to the anesthesia pre-admission clinic as well as inpatients scheduled for 
the operating room the next day would be screened via electronic medical record on a day-to-
day basis to determine if they are eligible to participate in the study. Eligibility screening would 
be determined based on their most recent surgical notes (i.e. whether the patient would likely 
undergo general anesthesia as well as NMB). 
Patients who are eligible would then be contacted and introduced to the study by a study team 
member for potential recruitment, at a minimum the day before the date of surgery in order to 
allow enough time for the patient to consider the risks and benefits of participation. 
16. Withdrawal of Participants
Patients may be withdrawn from the research study without their consent if they are found to 
not meet the study’s inclusion criteria, e.g.
-
Did not require general anesthesia for surgery,
-
Did not require NMB,
-
Did not receive neostigmine for NMB reversal,
-
Had a TOF count < 3 or a TOF ratio ≥ 0.9 fifteen minutes after neostigmine, or
-
Remained intubated in the immediate postoperative period.
As the study intervention is a one-time dose of the study drug in the OR, no further action 
should be required if the patient decides to later withdraw from the study. The study will be 
terminated when the number of participants has reached the required threshold.
17. Risk to Participants
The most common risks of sugammadex as listed by the FDA (5) include:
-
Nausea (23-26%)
-
Vomiting (11-15%)
-
Pain (36-52%)
Uncommon but serious risks of sugammadex include:
-
Hypotension (4-13%)
-
Tachycardia (2-5%)

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-
Bradycardia (1-5%)
-
Anaphylaxis (0.3%)
Notably, all of these are known to be risks of general anesthesia as well as surgery and are 
routinely monitored for and treated in the PACU.
18. Potential Benefits to Participants
All study subjects will have any residual NMB reversed, which will prevent any postoperative 
complications such as respiratory compromise or weakness. 
19. Compensation to Participants
N/A
20. Data Management and Confidentiality
Data to be collected include:
i. Baseline demographics: MRN, date of birth, sex (male/female), race (white, black, 
American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, 
two or more races), ethnicity (Hispanic or Latino, not Hispanic or Latino), weight (kg)
ii. Preoperative details: ASA status (I-IV)
iii. Surgery details: date of surgery, diagnosis, surgery, start case time (hr: min), end case 
time (hr: min)
iv. Anesthesia details: if succinylcholine was used (Y/N), total amount of rocuronium 
given (mg), the last dose of rocuronium that was given (mg), the time that the last 
dose of rocuronium was given (hr:min), neostigmine dose (mg), the time that 
neostigmine was given (hr: min), the time that the study drug was given (hr: min).
v. TOF ratio (0-1)
-
Before any paralytic is given at the start of the case
-
Before neostigmine is given at the end of the case
-
Before the study drug is given
-
30 minutes after PACU arrival
vi. TOF count (0-4 ± fade)
-
Before neostigmine is given at the end of the case
-
Before the study drug is given
vii. The time taken to achieve a TOF ratio of 0.9 (seconds).
viii. Postoperative details: if there was any of the following adverse effects: nausea, 
vomiting, bradycardia, tachycardia, hypotension (Y/N).

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Baseline demographics and postoperative complications will be collected for patients who were 
enrolled but did not meet the study inclusion criteria to receive the intervention drug and their 
data will be used as a control group for the safety outcomes.
The data collection form is in the Emory University REDCap database but a similar form has 
been attached to this protocol as an Excel spreadsheet. Data would be collected by the study 
team in the OR and PACU. Data will be stored on the Emory University REDCap and OneDrive 
databases and may also be sent confidentially between study team members through the 
Emory University Outlook email network. The REDCap and OneDrive databases as well as the 
Outlook email network are all secure, encrypted and password protected. Paper consent forms 
will be stored in a locked box in the principal investigator’s office at Grady Memorial Hospital. 
All data and records will be retained for at least 6 years following study completion.
Results will be reported in an aggregate form and in a de-identified manner. The form with 
protected health information (date of birth, date of surgery and MRN) will be recorded on a 
form separate to the form with data to be analyzed. Only study team members will have access 
to the form that links the study IDs with protected health information. Mr. David Boorman, the 
biostatistician for the Emory University Department of Anesthesiology, will conduct the data 
analysis in collaboration with the principal investigator.
If a participant declines to participate in all portions of the study, the participant will not be 
assigned a study ID number and the study team members will refrain from collecting any data 
on the participant.  If the participant agrees to participate in some portions of the study but not 
others, the participant will be assigned a study ID number and the study team members will be 
instructed to collect data only on those aspects of the study to which the participant has agreed 
to participate.  These procedures will help prevent unauthorized inclusion of the patient’s data 
in the database.
21. Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity
X
More than minimal risk 
Review our Data and Safety Monitoring Questionnaire and insert the relevant monitoring table 
at the end of this section. Also upload the completed questionnaire in the “Basic Study 
Information” smartform section in eIRB, question #8, as a separate document. 
Select one of the following:
☐ Medium Complexity
☐ High Complexity Category A

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☒ High Complexity Category B
The study team will review the safety endpoints (nausea, vomiting, bradycardia, hypotension) 
on a monthly basis for the duration of the study. These safety endpoints are collected at each 
study visit and recorded in the study database. Patients are routinely assessed for these side 
effects in the PACU by their bedside nurse as well as the anesthesia resident who is responsible 
for discharging them from the PACU. 
Subgroup n=6
Total N=36
Event
Assumed 
Probability 
Risk (upper 
end)
p<0.01
Safety cut
short if...
p<0.01
Safety cut
short if...
Nausea 
(high)
0.25
p=0.0046
n≥5
p=0.0086
n≥16
Vomiting 
(high)
0.15
p=0.0059
n≥4
p=0.0048
n≥12
Bradycardia 
(high)
0.05
p=0.0022
n≥3
p=0.0083
n≥6
Hypotension 
(high)
0.15
p=0.0059
n≥4
p=0.0048
n≥12
Using the binomial equation (see below), we calculated the probability of seeing a set number 
of patients in each group, if the actual probability in the normal surgical population is at the 
level specified in the 'assumed probability' column.  
For example, if the 'normal' probability of nausea is up to 25% (that is, the risk with treatment is 
the same as the risk under standard surgical conditions), then the chance of having 5 or more 
patients with nausea in any one treatment group is 0.0046, and the chance of having 16 or 
more patients with nausea in total is p=0.0048.  Since this is unlikely, we will reject the null 
hypothesis, and conclude that the actual risk in our trial is actually higher than that.  So if 5 or 
more patients report nausea in any one group or if 16 or more patients report nausea in total, 
this would trigger a suspension of the trial for further review.

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Data on serious adverse events such as death, perioperative cardiac arrest, and unplanned 
hospitalization as well as any other adverse events will also be collected up to the time of PACU 
discharge for both study participants as well as screen failures (participants who were recruited 
but not enrolled in the trial due to not fulfilling the study inclusion criteria).
Monitoring Table 3
DSMP Requirement
How this Requirement is Met 
Frequency
Responsible Party(ies)
Real-time review of 
participant data during 
initial data collection.
PI will review the data as it is 
being collected.
Every data 
collection 
timepoint
Expectation is that 
this happens every 
time you obtain 
information.
PI
Site Monitoring at pre-
determined intervals: 
The Principal Investigator 
has a responsibility to 
ensure that the study is 
following all aspects of 
the protocol. 
There should be a standard 
operating procedure to review 
data (whether a sample or 
100%) at pre-determined 
intervals to ensure that there is 
adequate documentation of 
critical elements such as 
eligibility criteria. Monitoring is 
required at the following 
timepoints (but may be done 
more frequently):

study initiation  

at least every six months 
while participants are 
receiving intervention 
and 

annually while 
participants are in 
follow-up
Every 6 months
At a minimum, a 
review is required 
annually when no 
one has been 
enrolled or the 
study is in long 
term follow up. 
Additional risk-
based interim 
monitoring may be 
required at least 
once every 12-24 
weeks based on the 
site activity, to 
include the 
possibility of 
remote monitoring. 
PI (self-assessment 
tool)
Delegate a responsible 
party for each 
requirement below. 
Self-assessment is 
acceptable*.
Self-assessment: a 
process for self-
assessment of 
protocol compliance 
and data integrity 
which can be part of 
an overall DSMP. See 
CTAC’s self-
assessment tool on 
their webpage. 

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A longer frequency 
could be 
acceptable with 
justification about 
risk to participants.
100% review of 
regulatory files
DCTR will review all regulatory 
files at study initiation as well as 
on an annual basis, either in 
electronic or paper form.
At study initiation 
& annually
Reviewed at a 
minimum of first 
and close-out visits
DCTR
100% review of consent 
forms
DCTR will review all consent 
forms on a monthly basis.
Every month
DCTR
Review of credentials, 
training records, the 
delegation of 
responsibility logs (if 
applicable)
DCTR will review the credentials 
of all study personnel at study 
initiation and on an annual 
basis.
At study initiation 
& annually
DCTR
Comparison of case 
report forms (CRF) to 
source documentation 
for accuracy and 
completion
PI will compare CRF to the 
source documentation in the 
patient’s Epic charts on a 
monthly basis.
Every month
PI
Review of 
documentation of all 
adverse events
PI will review all adverse events 
as reported on a monthly basis.
Every month
PI
Monitoring of critical 
data points (eligibility, 
study endpoints, etc.)
PI will monitor all critical data 
points on a monthly basis.
Every month
PI
Laboratory review of 
processing and storage 
of specimens
N/A
N/A 
Reviewed at first 
and close-out visits 
and at least 
biannually
N/A
Assessment of laboratory 
specimens stored locally
N/A
N/A
N/A
Test article 
accountability review
Grady Pharmacy IDS will review 
the study drug accountability 
records at least every 6 months.
Every 6 months
Reviewed at first 
and close-out visits 
and at least 
biannually
Grady Pharmacy IDS

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Accountability logs, 
dispensing records, and 
other participant records 
Grady Pharmacy IDS will review 
the study drug records at least 
every 6 months.
Every 6 months
At least biannually
Grady Pharmacy IDS
For FDA regulated 
studies, the following 
requirements apply:
Timing, frequency, 
and intensity of 
monitoring
Monitoring methods 
(may include centralized, 
on-site, and self-
assessment)
On-site & Self-assessment
Every 6 months
PI
*For international studies, you are required to engage a CRO that is working in the site country and/or to 
consult with Emory’s legal counsel regarding compliance with the country’s clinical research regulations.
DCTR: Emory University Department of Anesthesiology Division of Clinical and Translational 
Research staff member
IDS: Investigational Drug Services
PI: Principal Investigator
22. Provisions to Protect the Privacy Interest of Participants
The research procedures are not beyond what is routinely used in a patient’s intraoperative and 
postoperative anesthetic management. The patient will be given the option to not interact with 
study team members whenever he/she is not comfortable. The research team will contact the 
subject up to the time of discharge from the PACU, and only beyond that if necessary (e.g. if 
there is a significant adverse event that may or may not be related to the study).
23. Economic Burden to Participants
N/A
24. Informed Consent 
We will be informing and consenting patients in the anesthesia pre-admission clinic. This 
consent will be checked on the day of surgery itself to ensure ongoing consent. The principal 
investigator will be the one consenting study participants. Study subjects will be informed that 
participation in the study has no bearing on their clinical care, and will be given the opportunity 
to withdraw from the study at any time point.
The consent form has been attached to this protocol.
25. Setting
This is a single-site study at the Grady Memorial Hospital. Potential participants will be 
identified and recruited at the anesthesia pre-admission clinic on site. Research procedures will 
be performed in the main operating room and ambulatory surgery center on site.

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26. Resources Available
The study drug and equipment required for the study are all in routine clinical use at the Grady 
Memorial Hospital. As the inclusion criteria are broad and there is an average of 20-30 cases 
per weekday of elective surgeries requiring tracheal intubation and NMB, we anticipate that 
there would be minimal problems in recruiting the required number of suitable subjects within 
the aforementioned recruitment period. We will be briefing the anesthesiology department 
staff prior to the study commencement on the details of this research study.
27. Multi-Site Research When Emory is the Lead Site
N/A
28. References
1.
Appiah-Ankam J, Hunter JM. Pharmacology of neuromuscular blocking drugs. Continuing 
Education in Anaesthesia Critical Care & Pain. 2004;4(1):2-7.
2.
Murphy G, De Boer HD, Eriksson LI, Miller RD. Reversal (Antagonism) of Neuromuscular 
Blockade. In: Gropper MA, editor. Miller’s Anesthesia. 9th ed. Philadelphia, PA: Elsevier, Inc.; 
2020. p. 832-64.e5.
3.
Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, et al. A novel concept 
of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a 
cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41(2):266-70.
4.
Gijsenbergh F, Ramael S, Houwing N, van Iersel T. First human exposure of Org 25969, a 
novel agent to reverse the action of rocuronium bromide. Anesthesiology. 2005;103(4):695-
703.
5.
Merck Sharp & Dohme Corp. BRIDION(R) (sugammadex) Labeling - Package Insert. Silver 
Spring, MD: U.S. Food and Drug Administration; 2021 [Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022225s007s009lbl.pdf.
6.
Kopman AF. Neostigmine versus sugammadex: which, when, and how much? 
Anesthesiology. 2010;113(5):1010-1.
7.
Carvalho H, Verdonck M, Cools W, Geerts L, Forget P, Poelaert J. Forty years of 
neuromuscular monitoring and postoperative residual curarisation: a meta-analysis and 
evaluation of confidence in network meta-analysis. Br J Anaesth. 2020;125(4):466-82.
8.
Raval AD, Uyei J, Karabis A, Bash LD, Brull SJ. Incidence of residual neuromuscular 
blockade and use of neuromuscular blocking agents with or without antagonists: A systematic 
review and meta-analysis of randomized controlled trials. J Clin Anesth. 2020;64:109818.
9.
Raval AD, Anupindi VR, Ferrufino CP, Arper DL, Bash LD, Brull SJ. Epidemiology and 
outcomes of residual neuromuscular blockade: A systematic review of observational studies. J 
Clin Anesth. 2020;66:109962.
10.
Ledowski T, O'Dea B, Meyerkort L, Hegarty M, von Ungern-Sternberg BS. Postoperative 
Residual Neuromuscular Paralysis at an Australian Tertiary Children's Hospital. Anesthesiol Res 
Pract. 2015;2015:410248.

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11.
Klucka J, Kosinova M, Krikava I, Stoudek R, Toukalkova M, Stourac P. Residual 
neuromuscular block in paediatric anaesthesia. Br J Anaesth. 2019;122(1):e1-e2.
12.
Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex 
versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 
2017;8(8):Cd012763.
13.
Kirkegaard H, Heier T, Caldwell JE. Efficacy of tactile-guided reversal from cisatracurium-
induced neuromuscular block. Anesthesiology. 2002;96(1):45-50.
14.
Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose-finding study 
for reversal of shallow residual neuromuscular block. Anesthesiology. 2010;113(5):1054-60.
15.
Pongrácz A, Szatmári S, Nemes R, Fülesdi B, Tassonyi E. Reversal of neuromuscular 
blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. 
Anesthesiology. 2013;119(1):36-42.
16.
Aouad MT, Alfahel WS, Kaddoum RN, Siddik-Sayyid SM. Half dose sugammadex 
combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-
induced deep neuromuscular blockade: a cost-saving strategy. BMC Anesthesiol. 2017;17(1):57.
17.
Lobaz S, Sammut M, Damodaran A. Sugammadex rescue following prolonged 
rocuronium neuromuscular blockade with 'recurarisation' in a patient with severe renal failure. 
BMJ Case Rep. 2013;2013.
18.
Carollo DS, White WM. Postoperative Recurarization in a Pediatric Patient After 
Sugammadex Reversal of Rocuronium-Induced Neuromuscular Blockade: A Case Report. A A 
Pract. 2019;13(6):204-5.
19.
Fresenius Kabi USA. Neostigmine Methylsulfate Labeling - Package Insert. Silver Spring, 
MD: U.S. Food and Drug Administration; 2021 [Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/203629s003lbl.pdf.
20.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis 
program for the social, behavioral, and biomedical sciences. Behav Res Methods. 
2007;39(2):175-91.
21.
KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in 
Chronic Kidney Disease. Kidney Int. 2021;99(3s):S1-s87.
22.
Goldberg E, Chopra S. Child-Pugh classification of severity of cirrhosis: UpToDate, Inc.; 
2022, Apr [Available from: 
https://www.uptodate.com/contents/image?imageKey=GAST%2F78401.
23.
El-Khateeb E, Darwich AS, Achour B, Athwal V, Rostami-Hodjegan A. Review article: time 
to revisit Child-Pugh score as the basis for predicting drug clearance in hepatic impairment. 
Aliment Pharmacol Ther. 2021;54(4):388-401.
29. Protocol Checklist
Please note that protocol sections with an asterisk (*) should always be included in the protocol; if 
the section does not have an asterisk, and you have not included the section in the protocol, the 
IRB will consider it your attestation that the section does not apply to your study.

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Protocol Section
Added 
to the 
protoc
ol?
External Collaborators- if applicable, add each external collaborator information and 
indicate whether that institution’s IRB will review (or has already reviewed) that individual’s 
engagement in human participants research activities)  
☐ Yes
Funding Source*: Include the information for the funding entity for this study.  Please 
explain if this study is covered by a sub-award or other pertinent information. Say 
“department” if you do not have any other funding.
☒ Yes
Objectives*: Describe the purpose, specific aims, or objectives and state the hypotheses to 
be tested
☒ Yes
Background*: Describe the relevant prior experience and gaps in current knowledge. 
Describe any relevant preliminary data. Provide the scientific or scholarly background for, 
the rationale for, and significance of the research based on the existing literature and how 
will it add to existing knowledge
☒ Yes
Study Endpoints*: Describe the primary and secondary study endpoints. Describe any 
primary or secondary safety endpoints. 
☒ Yes
Study Intervention/Investigational Agent*: Describe the study intervention and/or 
investigational agent (e.g., drug, device) that is being evaluated.  
☒ Yes
Drug/Device Handling: If the research involves drugs or devices, describe your plans to store,
handle, and administer those drugs or devices so that they will be used only on participants 
and be used only by authorized investigators.
If using a drug, explain if the control of the drug is managed by IDS (or VA/Grady/CHOA 
research pharmacies). If not, provide IDS exemption document.
If a device, explain how the device is being stored and managed.
☒ Yes
If the drug is under an FDA REMS, plan to complete the REMS checklist found here, on the 
IRB website.
☐ Yes
If the drug is considered a controlled substance, make sure you have filled out this form.
☐ Yes
If applicable, identify the holder of the IND/IDE/Abbreviated IDE. An Emory investigator who 
holds an IND or IDE is considered to be a Sponsor-Investigator (S-I). If the study is under an 
S-I, review this section of our website for additional requirements.
☐ Yes

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Procedures involved*: Describe and explain the study design and include a study schema.  
Describe all research procedures being performed and when they are performed, including 
procedures being performed to monitor participants for safety or minimize risks
☒ Yes
Procedures-Minimizing risk*: describe the procedures performed to lessen the probability 
or magnitude of risks.
☒ Yes
Procedures- Drug/Device Use: describe all drugs and devices used in the research and the 
purpose of their use and their regulatory approval status
☒ Yes
Procedures-Source Records*: describe source records that will be used to collect data 
about participants. Attach all surveys, scripts, and data collection forms to the submission.
☒ Yes
Procedures-Data collection*: describe what data will be collected during the study and how 
that data will be obtained
☒ Yes
Procedures- Long Term Follow Up*: once all research-related procedures are complete, 
what data will be collected during this period.  If no data is collected after procedures are 
completed, please state in the submission.
☒ Yes
Data and Specimen Banking: describe where the specimens will be stored, how long they 
will be stored, how the specimens will be accessed, and who will have access to the 
specimens.  Depending on the volume and nature of the collection, this may require a 
separate repository-specific IRB submission. The VA Data Repository SOP is required if the 
study is creating a data repository at the Atlanta VA.
List the data to be stored or associated with each specimen.
Describe the procedures to release data or specimens, including the process to request a 
release, approvals required for release, who can obtain data or specimens, and the data to 
be provided with specimens.
☒ Yes
Sharing of Results with Participants*: Describe whether results (study results or individual 
subject results, such as results of investigational diagnostic tests, genetic tests, or incidental 
findings) will be shared with participants or others (e.g., the participant’s primary care 
physicians) and if so, describe how the results will be shared If applicable (e.g. for studies 
involving scans and/or panels of exploratory testing on specimens)
Plan for managing the types of findings that might arise. This should include any secondary 
findings that are being sought actively, findings that might be anticipatable, and findings 
that might be un-anticipatable. 
Plan for recognizing, analyzing, and handling incidental findings and how incidental findings 
will be communicated to participants during the consent process. If the plan is not to 
☒ Yes

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disclose any findings, then this should be included. This plan might include the option for 
participants to opt-out of receiving incidental findings.
Description of the research team’s responsibilities following disclosure of a finding. This 
should detail educational information about the nature of the finding, how to seek care 
from a clinician or specialist, obtaining health insurance to secure treatment, and/or referral 
to a clinical specialist, if one is required. 
Reminder to include language in the consent form to let the participants know your plans 
for this – see Modular Language for Informed Consent Forms on IRB website)
Study timelines*: describe the duration of an individual participant’s participation in the 
study; anticipated time to enroll all study participants and the estimated date for the 
investigators to complete this study (complete primary analyses)
☒ Yes
Inclusion and Exclusion Criteria*: describe how individuals will be screened for eligibility 
and the criteria that define who will be included or excluded in your final study sample 
☒ Yes
Population*: describe the study popualation and indicate specifically whether you will 
include or exclude each of the following special populations: 

Adults unable to consent

Individuals who are not yet adults (infants, children, teenagers)

Pregnant women

Prisoners
Note: you cannot exclude people with limited English proficiency unless you can 
demonstrate the scientific need for such exclusion.
Community Participation: For studies aimed at addressing issues that affect a certain 
community or group: How, if at all, will this study involve people from the target community 
in the design of the study? Conduct of the study? How will the results of the research be 
shared with the participants and/or the target community/ies?  
If studying Race or Ethnicity, have you defined these terms, and explained their proposed 
mechanism of action if these characteristics will be used in an explanatory model?
☒ Yes
Research with pregnant women, fetuses, or neonates: review this checklist to verify you 
have provided enough information to ensure the safety and well-being of this population.
☐ Yes
Research with neonates of uncertain viability: review this checklist to verify you have 
provided enough information to ensure the safety and well-being of this population.
☐ Yes

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Research involving prisoners: review this checklist to verify you have provided enough 
information to ensure the safety and well-being of this population.
☐ Yes
Research involving children: review this checklist to verify you have provided enough 
information to ensure the safety and well-being of this population.
☐ Yes
Research involving cognitively impaired adults: review this checklist to verify you have 
provided enough information to ensure the safety and well-being of this population.
☐ Yes
Research involving economically or educationally disadvantaged persons: describe the 
additional safeguards that have been included in the study to protect the rights and welfare 
of these subjects
☐ Yes
Local Number of Participants*: Indicate the total number of participants to be accrued 
locally. If applicable, distinguish between the number of participants who are expected to 
be enrolled and screened, and the number of participants needed to complete the research 
procedures (i.e., numbers of participants excluding screen failures.) 
Provide your projected enrolling goals, including the percentage of participants according to 
sex and race.   
☒ Yes
Recruitment Methods*: Describe when, where, and how potential participants will be 
recruited.  Describe the source of participants. Describe the methods that will be used to 
identify potential participants.  Describe materials that will be used to recruit participants. 
Attach copies of these documents with the application. 
If including advertisements, attach the final copy of them. When advertisements are taped 
for broadcast, attach the final audio/videotape. You may submit the wording of the 
advertisement before taping to preclude re-taping because of inappropriate wording, 
provided the IRB reviews the final audio/videotape. Describe the amount and timing of any 
payments to participants. Reimbursement for expenses/travel?
If using contests or raffles as incentive, you must offer entry to all potential participants, not 
just those who enroll in the study/complete study-related procedures, per Georgia State 
Law.
All research recruitment through social media needs to follow this guidance, which does not 
allow the use of personal social media accounts for some recruitment activities.
☒ Yes
Withdrawal of Participants*: Describe anticipated circumstances under which participants 
will be withdrawn from the research without their consent. Describe any procedures for 
orderly termination. Describe procedures that will be followed when participants withdraw 
from the research, including partial withdrawal from procedures with continued data 
collection.
☒ Yes

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Risk to Participants*: List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the participants related to the participant's participation in the research. 
Include as may be useful for the IRB’s consideration, a description of the probability, 
magnitude, duration, and reversibility of the risks. Consider physical, psychological, social, 
legal, and economic risks.
If applicable, indicate which procedures may have risks to the participants that are currently 
unforeseeable.
If applicable, indicate which procedures may have risks to an embryo or fetus should the 
subject be or become pregnant.
If applicable, describe risks to others who are not participants.
☒ Yes
Potential Benefits to Participants*: Describe the potential benefits that individual 
participants may experience from taking part in the research. Include as may be useful for 
the IRB’s consideration, the probability, magnitude, and duration of the potential benefits.
Indicate if there is no direct benefit. Do not include benefits to society or others.
☒ Yes
Compensation to Participants*: Describe if/how subjects will be compensated for 
participation in this study. Indicate what method compensation will be delivered (e.g. cash, 
gift card, school credit). Describe the amount and timing of any payments to participants.  
How much?  What kind?  Is tax information required? (if so, must be reflected in the 
informed consent form). Will payments be pro-rated if a participant withdraws early?
☒ Yes
Data Management and Confidentiality*: Describe the data analysis plan, including any 
statistical procedures or power analysis. Describe the steps that will be taken to secure the 
data (e.g., training, authorization of access, password protection, encryption, physical 
controls, certificates of confidentiality, and separation of identifiers and data) during 
storage, use, and transmission. Describe any procedures that will be used for the quality 
control of collected data. 
☒ Yes
Describe how data or specimens will be handled study-wide*: What information will be 
included in that data or associated with the specimens?
•
Where and how data or specimens will be stored?
•
How long the data or specimens will be stored?
•
Who will have access to the data or specimens?
•
Who is responsible for receipt or transmission of the data or specimens?
•
How data or specimens will be transported?
☒ Yes
Data Monitoring and Participants Safety (if this study is more than minimal risk, this 
section is required): 
☒ Yes

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Ensure that you review our Data and Safety Monitoring plan guidance for specific details 
about this section, and examples of what the IRB will be requiring according to the level of 
risk.
If a DSMB is needed, please describe the composition of the board (if not already detailed 
in the protocol).  Review this guidance for more information.  If the sponsor protocol does 
not contain all required information, please in this section. 
Describe the plan to periodically monitor the data at the site level according to risk level. 
Include the appropriate completed monitoring table, if applicable. 
Description of the plan for notifying the IRB of reportable events, whether the sponsor 
requires reporting above and beyond the Emory IRB reporting requirements, and if so, a 
description of the requirements and plan for meeting them. 
Please address the specific details below. If deemed not applicable, please provide 
rationale:
Subject safety:

Specific subject safety parameters 

Frequency of subject safety observations

Individual responsible for safety monitoring

Subject stopping rules – under what conditions will a subject be removed from 
study participation and who will make the decision?

Study stopping rules - under what conditions will the study be modified or stopped 
and who will make the decision?

Reporting mechanisms (i.e. Deviations, adverse events, UPs)
Data Integrity:

Specific data elements to be reviewed

Frequency of monitoring data, points in time, or after a specific number of 
participants

Individual responsible for data monitoring
Additional considerations for FDA regulated trials 
Depending on the procedures affecting risks to participants, the site monitoring plan should 
specify:

Categorization of activities done centrally and those on-site if applicable

Monitoring methods (may include centralized/remote, on-site, and self-monitoring)

Reference to any tools used (i.e. checklists)

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
Identification of events that may trigger changes

Identification of deviations or failures that would be critical to study integrity
Provisions to Protect the Privacy Interests of Participants*: 

Describe the steps that will be taken to protect participants’ privacy interests. “Privacy 
interest” refers to a person’s desire to place limits on whom they interact with or whom 
they provide personal information.

Describe what steps you will take to make the participants feel at ease with the 
research situation in terms of the questions being asked and the procedures being 
performed. “At ease” does not refer to physical discomfort, but the sense of 
intrusiveness a participant might experience in response to questions, examinations, 
and procedures.

Indicate how the research team is permitted to access any sources of information about 
the participants.
☒ Yes
Economic Burden to Participants*: Describe any costs that participants may be responsible 
for because of participation in the research.
☒ Yes
Consent Process*: Describe where the consent process will take place, any waiting period 
available between informing the prospective subject and obtaining the consent; and the 
process to ensure ongoing consent.
Describe the role of the individuals listed in the application as being involved in the consent 
process; the time that will be devoted to the consent discussion; steps that will be taken to 
minimize the possibility of coercion or undue influence; and steps that will be taken to 
ensure the participants’ understanding.
Note: If you are planning to obtain consent via electronic signature, please review this 
document. Additional guidance on consent documentation and process can be found on our 
website, under the consent toolkit.
☒ Yes
Consent Process-Non-English-Speaking Participants*: 
Indicate what language(s) other than English are understood by prospective participants or 
representatives.
If participants who do not speak English will be enrolled, describe the process to ensure that 
the oral and written information provided to those participants will be in that language. 
Indicate the language that will be used by those obtaining consent.
If you checked N/A, please provide reasoning of why subjects with limited English 
proficiency are excluded. 
Note: if you stated that subjects with LEP will be enrolled, you are approved for the use of 
the Emory IRB short forms.  Please read the guidance about the use of short forms here.
☐ Yes

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Consent Process-Children: After determining if the subject is a child per GA law (or if 
enrolled outside GA, per state/country law), please describe whether parental permission 
will be obtained from:

Both parents unless one parent is deceased, unknown, incompetent, or not reasonably 
available, or when only one parent has legal responsibility for the care and custody of 
the child.

One parent even if the other parent is alive, known, competent, reasonably available, 
and shares legal responsibility for the care and custody of the child.
Describe whether permission will be obtained from individuals other than parents, and if so, 
who will be allowed to provide permission.  Describe the process used to determine these 
individuals’ authority to consent to each child’s general medical care.
When assent of children is obtained describe whether and how it will be documented per 
Emory Policies and Procedures
☐ Yes
Consent Process-Cognitively Impaired Adults:  describe the process to determine whether 
an individual is capable of consent. The IRB allows the person obtaining assent to document 
assent on the consent document and does not routinely require assent documents and does 
not routinely require children to sign assent documents.
☐ Yes
Consent Process-Adults Unable to Consent:  List the individuals from whom permission will 
be obtained in the order of priority. (E.g., durable power of attorney for health care, a court-
appointed guardian for health care decisions, spouse, and adult child.)
For research conducted in the state, review “46 LEGALLY AUTHORIZED REPRESENTATIVES 
AND SURROGATE CONSENT” to be aware of which individuals in the state meet the 
definition of “legally authorized representative.”
For research conducted outside of the state, provide information that describes which 
individuals are authorized under applicable law to consent on behalf of a prospective 
subject to their participation in the procedure(s) involved in this research. 
Describe the process for the assent of the participants. Indicate whether:

Assent will be required of all, some, or none of the participants. If some, indicated, 
which participants will be required to assent and which will not.

If assent will not be obtained from some or all participants, an explanation of why not.
Describe whether the assent of the participants will be documented and the process to 
document assent. The IRB allows the person obtaining assent to document assent on the 
☐ Yes

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consent document and does not routinely require assent documents and does not routinely 
require participants to sign assent documents
Waiver or Alteration of Consent Process (consent will not be obtained, required 
information will not be disclosed, or the research involves deception) 
Review the Emory IRB waiver document to ensure you have provided sufficient information 
for the IRB to make these determinations.
If the research involves a waiver of the consent process for planned emergency research, 
please review the “CHECKLIST: Waiver of Consent for Emergency Research (HRP-419)” to 
ensure you have provided sufficient information for the IRB to make these determinations.
☐ Yes
Setting*: Describe the sites or locations where your research team will conduct the research 
including where the subject will be identified and recruited, where the research procedures 
will be performed, and if you will involve a community advisory board.  For research 
conducted outside the organization and its affiliates describe the site-specific regulations or 
customs affecting the research outside the organization and the local scientific and ethical 
review structure outside the organization.
☒ Yes
Resources Available*: Describe the resources available to conduct the research such us the 
feasibility of recruiting the required number of suitable participants within the agreed 
recruitment period; describe the time that you will devote to conducting and completing 
the research; describe the availability of medical or psychological resources that participants 
might need as a result of an anticipated consequences of the human research; describe your 
process to ensure that all persons assisting with the research are adequately informed 
about the protocol, the research procedures, and their duties and functions.
☒ Yes
Multi-Site Research when Emory is the Lead Site:
Study -Wide Number of Participants: indicate the total number of participants to be accrued 
across all sites.
Study-Wide Recruitment Methods: If this is a multicenter study and participants will be 
recruited by methods not under the control of the local site (e.g., call centers, national 
advertisements) describe those methods.  
Describe when, where, and how potential participants will be recruited.
Describe the methods that will be used to identify potential participants.
Describe materials that will be used to recruit participants. 
Describe the processes to ensure communication among sites. See “WORKSHEET: 
Communication and Responsibilities (HRP-830).” All sites have the most current version of 
the protocol, consent document, and HIPAA authorization.
All required approvals (initial, continuing review and modifications) have been obtained at 
each site (including approval by the site’s IRB of record).
All modifications have been communicated to sites and approved (including approval by the 
site’s IRB of record) before the modification is implemented.
☒ Yes

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All engaged participating sites will safeguard data, including secure transmission of data, as 
required by local information security policies.
All local site investigators conduct the study in accordance with applicable federal 
regulations and local laws. 
All non-compliance with the study protocol or applicable requirements will reported in 
accordance with local policy
Describe the method for communicating to engaged participating sites (see “WORKSHEET: 
Communication and Responsibilities (HRP-830)”):

Problems (inclusive of reportable events).

Interim results.

The closure of a study
If this is a multicenter study where you are a participating site/investigator, describe the 
local procedures for maintenance of confidentiality. (See “WORKSHEET: Communication and 
Responsibilities (HRP-830).”)

Where and how data or specimens will be stored locally?

How long the data or specimens will be stored locally?

Who will have access to the data or specimens locally?

Who is responsible for receipt or transmission of the data or specimens locally?

How data and specimens will be transported locally?