Comparative Human Factors Evaluation of Two Nasal Naloxone Administration Devices: NARCAN^® Nasal Spray and Naloxone Prefilled Syringe with Nasal Atomizer

Opioid overdose fatalities in the United States have drastically risen over the past two decades, leading to the development of training initiatives for nonmedical first responders and bystanders on when and how to administer the opioid reversal agent naloxone [1]. This authorization and promotion of lay users to respond to opioid overdoses prior to the arrival of emergency medical services (EMS) has already resulted in a reduction in opioid fatalities in areas with increased public access to naloxone [2, 3]. The goal of human factors research is to design devices that address the challenges faced by different user groups in various use environments and thus reduce the risks associated with using such products. Naloxone use by nonmedical personnel poses human factors design challenges as the medication administration device needs to effectively guide the user to correctly administer naloxone during time-critical emergency overdose scenarios.

Naloxone was developed in the 1960s and was the first opioid overdose reversal agent largely free of adverse effects, resulting in it quickly becoming the standard rescue medication for overdose management [2, 3]. Naloxone is currently available as a prefilled syringe (PFS) that the user can build into an intramuscular (IM) or intranasal (IN) kit by separately purchasing and adding a standard needle or nasal atomizer, respectively. Compared with IM naloxone, use of IN naloxone reduces the risk of a needlestick, which is important given the high prevalence of blood-borne illnesses among those with opioid use disorders [3]. However, the IN PFS kit is an off-label use [4]. The Food and Drug Administration (FDA) recently approved administration of naloxone by bystanders via NARCAN^® Nasal Spray (approved in 2015; ADAPT Pharma, Inc., Radnor, PA) [3]. NARCAN^® Nasal Spray (Fig. 1) costs $125 for two doses [5], whereas a PFS and independently added nasal atomizer (PFS-NA) (Fig. 2) costs approximately $44 for a single dose [5, 6]. The average insurance co-pay for both products, either the two doses of NARCAN^® Nasal Spray or the one dose of a PFS-NA, is approximately $17 [6‐8].

The need for nonmedical personnel to appropriately deliver naloxone during opioid overdoses is well known and increasing. However, the safety of lay prehospital naloxone administration has not been established [9], and standardized medication administration training programs are limited. Additionally, the naloxone PFS-NA was recalled by the FDA in 2016 because the nasal atomizer was not reliably converting the fluid medication into a spray [10]. Despite these uncertainties, studies suggest that the risks involved in lay naloxone administration outweigh the dangers posed by an opioid overdose, particularly when users are not trained in other respiratory support methods [3].

Prior usability research found that no untrained, and about 60% of trained, users were able to successfully administer a full dose of naloxone using a PFS-NA [11], whereas > 90% of untrained users were able to successfully administer a full dose using NARCAN^® Nasal Spray [12]. These studies provide information about lay users’ ability to administer naloxone but do not provide insights on why users commit more errors when using a PFS-NA.

Human factors is a discipline that focuses on how people interact with products in specific use environments (cf. [13]). The goal of human factors research is to optimize the design of a product to match the capabilities and limitations of the users, thus making product use safer and more effective [14]. In this paper, we conducted a human factors evaluation of NARCAN^® Nasal Spray versus a PFS-NA by assessing the ease of use of administering each IN naloxone product in time-critical emergency situations. We hypothesized that increased task complexity and coupling lead to greater risk of incorrectly administering naloxone when using a PFS-NA compared with the NARCAN^® Nasal Spray.

For this study, we employed a systems-oriented human factors evaluation approach to determine the differences in task complexity and risk between NARCAN^® Nasal Spray and a PFS-NA. This article does not contain any studies with human participants or animals performed by any of the authors.

We first conducted a literature review to create an independent list of use requirements for different user groups. We used Google Scholar with the search terms {“naloxone”}, {“Narcan”}, {“opioid crisis”}, and {“opioid overdose”} as well as similar variations to build a database of articles. We also searched resources from government and public awareness organizations, such as the Centers for Disease Control and Prevention (CDC) and the Association for Addiction Professionals, for information about opioid abuse and opioid overdose rescue procedures. This search was conducted in October 2018. No papers were excluded based on publication date, but additional weight was given to newer articles citing current opioid use and treatment regimens.

We then constructed a task analysis of NARCAN^® Nasal Spray and a PFS-NA by performing a mock administration using each product’s respective Instructions for Use (IFU) (Figs. 3, 4). The intent of the task analysis was to determine the tasks, subtasks, and workflow involved in administering naloxone with each kit. We performed this analysis in accordance with the 2016 FDA guidance “Applying Human Factors and Usability Engineering to Medical Devices” [15].

Finally, we constructed a risk assessment of all administration tasks that were substantially different between NARCAN^® Nasal Spray and a PFS-NA. The goal of the risk assessment was to determine which tasks posed the greatest risk of preventing successful naloxone administration. We performed the assessment in accordance with the 2007 International Organization for Standardization standard “ISO 14971: Medical devices—Application of risk management to medical devices” [16].

The following sections describe the results for each stage of the human factors evaluation, which included exploring the use requirements for naloxone and conducting a task analysis and risk assessment of NARCAN^® Nasal Spray and a PFS-NA.

The opioid crisis is widespread, and naloxone temporarily mitigates the life-threatening respiratory depression that causes opioid overdose fatalities. Given the speed of illicit fentanyl, its rising use, and the risk of consuming opioids laced with fentanyl [25], saving opioid overdose victims’ lives increasingly depends on the ability of nonmedical first responders and lay bystanders to appropriately administer naloxone rescue treatments. This study evaluated the ease of use of administering IN naloxone in time-critical emergency situations with two different products: NARCAN^® Nasal Spray and a PFS-NA.

Opioid overdoses caused over 140,000 nonfatal emergency department visits and over 42,000 fatalities in 2017 [26, 27]. The symptoms of opioid overdose are pinpoint pupils, unconsciousness, and respiratory depression [28]; respiratory depression may cause death [3]. The treatment for opioid overdoses is to combat this suppressed breathing physically though cardiopulmonary resuscitation (CPR) and pharmacologically through naloxone administration.

Naloxone use in emergency opioid overdose situations is common and promoted for nonmedical users, making it important to evaluate this user group’s needs. Lay administration keeps overdose victims alive until EMS arrive. Lay users, however, often have minimal training on naloxone administration and are more likely to experience mental limitations due to stress in emergency situations. The human factors task and risk assessments revealed that compared with NARCAN^® Nasal Spray, a PFS-NA involved substantially more steps to complete the Preparation and Delivery tasks. The task simplicity of NARCAN^® Nasal Spray should thus aid lay users in correct medication administration.

Real-world findings from the Association for Addiction Professionals support the results from this study. Data indicate that a PFS-NA is difficult to assemble and that users commonly break or misuse kit components [29]. Our risk analysis strengthens usability study results from Edwards et al. [11] and Krieter et al. [12], which suggest that untrained users are unlikely to successfully administer naloxone using a PFS-NA and are more likely to successfully administer the medication using NARCAN^® Nasal Spray.

The primary limitation of this comparative human factors analysis was that the task analysis did not involve actual opioid users. Future research might include evaluating these products with opioid users or using an expanded set of human factors techniques, such as time-and-motion analysis. This would provide further insights into the safety of each IN naloxone administration method.

Training nonmedical personnel to use naloxone presents the human factors challenge of how best to design a safe and effective delivery system for lay users given the added mental constraints posed by emergency situations. From a human factors perspective, nonmedical emergency responders and bystanders are more likely to correctly and successfully administer NARCAN^® Nasal Spray than a naloxone PFS-NA.