A Usability Assessment of Intramuscular, Atomized Intranasal, and Nasal Spray Administration of Naloxone by Untrained Community Members
Phase: NA
Conditions: Harm Reduction, Opioid-use Disorder, Naloxone
Sponsor: State University of New York - Upstate Medical University

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Protocol: A usability assessment of intramuscular, atomized intranasal, and nasal spray 
administration of naloxone by untrained community members 
Primary Investigator: William Eggleston, PharmD 
 
Background: Opioid abuse and addiction is a growing epidemic both in the United States and globally. It 
impacts the health, social welfare, and economic stability of those directly affected and society as a 
whole. According to the National Institute on Drug Abuse there are approximately 2.1 million 
people in the United States with substance use disorders related to prescription opioid medications 
and another 467,000 addicted to heroin. Data from the Center for Disease Control National Vital 
Statistics System demonstrated that the number of drug poisonings involving opioid analgesics 
tripled from 2000 to 2014, and in 2010 opioid pain relievers were responsible for 82.8% of all 
unintentional deaths in the United States.1 In an attempt to combat this epidemic many states have 
implemented community-based opioid overdose prevention programs aimed at increasing 
resources to combat addiction and distributing naloxone to community members. These programs 
increase knowledge of overdose prevention and the factors that increase a person’s risk for 
overdose. Evaluations of these programs have also demonstrated that nonmedical bystanders are 
able to administer naloxone effectively after completing training.2 Naloxone can be administered 
intravenously, intramuscularly, or via inhalation. Opioid overdose prevention programs are typically 
initiated by local and state governments, which allows for interprogram variability regarding the 
route of naloxone administration used by community members. Pre-hospital data has 
demonstrated that intranasal naloxone is a safe and effective alternative to intravenous naloxone.3 
A usability assessment comparing a naloxone auto-injector (Evzio®) to the use of a nasal atomizer 
suggested that the route of administration did impact the rate of successful naloxone 
administration by nonmedical community members.4 Opioid overdose prevention programs 
typically utilize intranasal atomizers, nasal inhalers, or intramuscular administration routes. In 2016 
we conducted a usability assessment of naloxone administered by community members who 
received training on how to use the naloxone device they were assigned. Our data supported that 
intranasal administration with an atomizer or spray resulted in a higher administration success rate 
when compared to intramuscular injection. Recently, New York, along with many other states, 
passed legislation allowing individuals to purchase naloxone over-the-counter without a 
prescription. This legislation has drastically expanded access to naloxone, but has reduced the 
opportunity to train community members purchasing the medication. We plan to conduct a 
usability assessment of simulated naloxone in community members in the absence of training to 
assess the rate of successful administration and time to successful administration. 
Objectives: 
Primary: The successful administration of simulated naloxone without training. A successful 
administration will be defined as administration of the simulated naloxone to the mannequin head or 
simulated flesh pad within 7 minutes and without any critical errors (defined below). 
Secondary:  
-Total time required to successfully administer the simulated naloxone without training. 

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-Comparison of successful administration with standard and simplified instrubtions 
-Comparison of total time required for successful administration with standard and simplified 
instructions 
-Likert-item assessment of the usability of the simulated naloxone product 
-Likert-item assessment of usability of the naloxone administration instructions 
Design: Single site, open-label, randomized usability assessment of intramuscular, intranasal, and nasal 
spray administration of simulated naloxone using standard (package-insert) or simplified (developed by 
study team) instructions. A convenience sample of participants will consent to volunteer in the study at 
a public venue. Participants will provide verbal consent and will be randomly assigned a 
simulated naloxone kit containing either intramuscular standard, intramuscular simplified, intranasal 
standard, intranasal simplified, nasal spray standard, or nasal spray simplified administration materials. 
The participant will enter a use scenario station where they will be asked to assemble and administer 
the simulated naloxone kit to a mannequin (intranasal and nasal spray) or simulated flesh pad 
(intramuscular). The participant will be instructed to start and will be timed until the simulated naloxone 
has been successfully administered or 7 minutes has elapsed. The participant will be observed by one 
trained investigator who will assess for successful administration of the simulated naloxone and critical 
errors. The environment will contain distracters to mimic a community based setting. Once the 
participant has successfully administered the simulated naloxone or 7 minutes has elapsed the timer will 
be stopped. Successful administration of simulated naloxone will be defined as administration of the 
agent without any critical errors occurring (defined below). Data collected will include demographics 
(defined below), successful administration of simulated naloxone, product assessment information, 
instruction assessment information, and time to successful administration of simulated naloxone. 
Eligibility: healthy adults (18 years of age and older) at a public venue will be asked to participate in the 
study. Participants will be excluded if they are severely visually or hearing impaired (defined as: legally 
deaf, legally blind, unable to read print size provided on instructional handout, or unable to hear 
instructions from a research staff member), have previous naloxone administration training, are not 
English proficient, state that they may be pregnant, or they have previously participated in the trial.  
 
Statistical Methods: All data will be analyzed using IBM SPSS Statistics software. Demographics data will 
be analyzed using descriptive statistics for continuous measures and percentages for categorical 
measures. The successful administration of naloxone will be compared between groups using the Chi-
square test and a significant difference will be defined as a p-value of less than 0.05 for the result. The 
time to administration between groups will be assessed using a one-way ANOVA and a significant 
difference will be defined as a p-value of less than 0.05 for the result. The Likert-item data will be 
reported as percentage of response level and analyzed using a one-way ANOVA with a significant 
difference defined as a p-value of less than 0.05 for comparison between administration methods and 
instruction methods. 
 
Data Analysis/Interpretation: As stated above data will be collected to assess both the successful 
administration of and time to administration of naloxone. The rate of successful administration will be 

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reported as a percentage for each of the three groups and analyzed using the Chi-square test. 
Successful administration is defined as administration of the simulated naloxone within 7 minutes 
without committing any critical errors. Critical errors are as follows: 
 
Intranasal (atomizer): failure to remove both yellow caps from bristoject, failure to remove cap 
from simulated naloxone, failure to attach atomizer, failure to attach simulated naloxone, drug 
leak prior to administration, administration in only one nostril, and failure to administer within 
7 minutes. 
 
Intramuscular: failure to attach the needle to the syringe, failure to remove cap from simulated 
naloxone, failure to draw up >90% (0.9 mL) of the simulated naloxone, failure to puncture 
simulated flesh pad with needle, failure to push entire volume of fluid in the syringe into the 
simulated flesh pad, and failure to administer within 7 minutes. 
 
Intranasal (spray): failure to place the tip of the device into one nostril, failure to depress the 
device and release the simulated naloxone, failure to administer within 7 minutes. 
 
Time to successful administration will be reported using descriptive statistics (mean time to 
administration) and analyzed using a one-way ANOVA. Times for participants who commit a critical 
error or who do no administer the simulated naloxone within 7 minutes will not be included in the 
analysis. The Likert-item data will be reported as a median with an inter-quartile range and analyzed 
using a one-way ANOVA. 
 
A route of administration will be considered to be more user-friendly if it demonstrates a statistically 
significantly higher rate of successful administration compared to another route of administration. 
Additionally, a route or instruction type will be considered user preferred if the Likert-item data 
demonstrates a significantly better score on usability. 
 
Study Procedures: No study procedures will be performed on study participants. 
 
Diagram of Study Design: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants provide oral 
consent for the study and are 
randomized to an 
administration kit using web-
based randomization software. 
Participants are provided their 
randomly assigned kit. 
Participants are placed in the 
simulated overdose scenario 
and given 7 minutes to 
administer the simulated 
naloxone to the mannequin 
designated for their kit. 

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Works Cited 
1.  Volkow ND. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. 
https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-
congress/2016/americas-addiction-to-opioids-heroin-prescription-drug-abuse. Published 
May 14, 2014. Accessed June 24, 2016. 
2.  Clark AK, Wilder CM, Winstanley EL. A systematic review of community opioid overdose 
prevention and naloxone distribution programs. J Addict Med. 2014;8(3):153-163. 
3.  Barton ED, Colwell CB, Wolfe T, et al. Efficacy of intranasal naloxone as a needleless 
alternative for treatment of opioid overdose in the prehospital setting. J Emerg Med. 
2005;29(3):265-271. doi:10.1016/j.jemermed.2005.03.007. 
4.  Edwards ET, Edwards ES, Davis E, Mulcare M, Wiklund M, Kelley G. Comparative Usability 
Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. Pain Ther. 
2015;4(1):89-105. doi:10.1007/s40122-015-0035-9. 
  
Investigators observe the 
administration and record if the 
administration is successful, the 
time to administration, and the 
critical error that occurred if 
applicable. Survey data is 
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d