Abstract
Objective:
The objective of this systematic review was to assess the clinical, economic, and health resource utilization outcomes associated with the use of prefilled syringes in medication administration compared with traditional preparation methods.
Data Sources:
We conducted a systematic literature review to evaluate outcomes such as medication errors, wastage, time savings, and contamination in prefilled syringes. Our search encompassed multiple databases, including PubMed and Embase, for studies published between January 1, 2017, and November 1, 2022.
Study selection and data extraction:
Peer-reviewed publications meeting our inclusion criteria underwent rigorous screening, including title, abstract, and full-text article assessments, performed by two reviewers.
Data synthesis:
Among reviewed articles, 24 met our eligibility criteria. Selected studies were primarily observational (46%) and conducted in Europe (46%). Our findings indicated that prefilled syringes consistently reduced medication errors (by 10%-73%), adverse events (from 1.1 to 0.275 per 100 administrations), wastage (by up to 80% of drug), and preparation time (from 4.0 to 338.0 seconds) (ranges varied by drug type, setting, and dosage). However, there was limited data on contamination. Economically, prefilled syringes reduced waste and error rates, which may translate into overall savings.
Relevance to patient care and clinical practice:
This review highlights the value of prefilled syringes, which can streamline medication delivery, save nursing time, and reduce preventable medication errors. Moreover, prefilled syringes have the potential to minimize medication wastage, optimizing resource utilization and efficiency in health care settings.
Conclusion and relevance:
Our findings provide new insights into clinical and economic benefits of prefilled syringe adoption. These benefits include improved medication delivery and safety, which can lead to time and cost reductions for health care departments, hospitals, and health systems. However, further real-world research on clinical and economic outcomes, especially in contamination, is needed to better understand the benefits of prefilled syringes.
Keywords
Introduction
Medication administration is a vital aspect of health care provision. Injection and intravenous administration of small-molecule drugs are core functions of nearly every hospital department and inpatient care facility, representing millions of procedures daily. 1 Unfortunately, errors in the administration of medication, such as human mistakes in labeling and delivery, contamination, and adverse reactions due to improper technique, have significant adverse impacts on patient health outcomes. 2 The prevalence of preventable medication errors prompted the World Health Organization to launch the global patient safety challenge, Medication Without Harm, in 2017 to reduce severe and avoidable harm related to medicines by 50% over 5 years. 3 There are also product inefficiencies associated with current medication administration methods, such as drug wastage. One study estimated that up to 86% of prepared epinephrine syringes go unused or discarded in operating rooms and intensive care units (ICUs), 4 while wastage rates of 85% and 67% have been used in 2 recent economic analyses, respectively.5,6 Unused medication can result in negative economic implications for emergency departments, operating rooms, and ICUs. 4 Discarded medication can also harm the environment by accumulating in soil and waterways. 7 This can cause toxic and long-lasting effects in both humans and animals, leading to damage to ecosystems.7,8
Prefilled syringes offer a simple, self-contained solution for storage and administration of medication. Sometimes called “ready-to-administer,” prefilled syringes are typically filled and packaged by the manufacturer and delivered ready for use. Prefilled syringes have gained popularity in recent years due to their potential to mitigate the safety risks and negative economic and environmental impacts of conventional drug delivery modalities described above. Emerging research indicates that the use of prefilled syringes can reduce error rates and wastage, as well as expedite preparation and administration times.9,10 The benefits of these increases in efficiency can alleviate pressure placed on health care workers through time savings and minimization of complex steps. In addition, the use of prefilled syringes has been associated with reduced risk of contamination, as there are fewer preparation steps that can introduce bacteria. 10 Despite the potential value of prefilled syringes, no systematic literature reviews (SLRs) have been conducted to date to assess the holistic body of evidence on the clinical utility and economic impact of this medication delivery modality.
As of 2019, approximately 2% of acute liquid injectable small-molecule drugs <50 mL were delivered via ready-to-administer systems, representing roughly 39 billion doses worldwide annually. 11 Given the potential impact of increasing usage of prefilled syringes, the objective of this research was to comprehensively and systematically synthesize available literature on the clinical utility and economic impact of prefilled syringes for administration of medications compared with conventional preparation methods, such as vial and syringe.
Methods
An SLR was conducted in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses for systematic review protocols (PRISMA-P) 12 by the study authors, who are health services researchers with technical and subject matter expertise in medication administration, anesthesiology, health economics, and SLR methodologies. Literature searches were conducted in PubMed, EMBASE, CENTRAL, and Google Scholar using controlled vocabulary (eg, medical subject headings [MeSH] in PubMed, Emtree in Embase) and free-text searches. The search strategy is presented in Supplemental Materials. References cited in final review publications were also assessed for eligibility.
Eligibility for inclusion was defined according to Population, Intervention, Comparator, Outcome, and Study Design (PICOS) criteria (Table 1). Studies reporting on the following outcomes of prefilled syringes use were considered for inclusion: Clinical (preventable adverse events [pADEs] and Sterility/Contamination), Economic (Total Cost and Modeled Outcomes), and Health Resource Utilization (Unused Drug/Wastage and Time Savings). Studies published between January 1, 2017, and November 1, 2022, that reported results of implementing a prefilled syringes program and modeled analyses were eligible for inclusion. Only patient populations receiving medication from a health care provider in a health care setting were included. Studies were required to be written in English, German, French, Spanish, Italian, and Dutch to be eligible for inclusion. Each article was assessed independently by 2 reviewers, and any conflicts were adjudicated by a third reviewer.
SLR Eligibility Criteria.
Abbreviations: pADE, preventable adverse drug event; SLR, systematic literature review.
Following final article selection, reviewers abstracted data and conducted qualitative synthesis to summarize findings. Quality and risk of bias assessments of included studies were conducted using the following assessment tools: National Institutes of Health’s Quality Assessment Tool for Controlled Intervention Studies, Observational Cohort and Cross-Sectional Studies, Before and After (Pre and Post) with no Control Group, and the Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations.13,14 Stability studies were excluded from the quality assessment as these are quality test studies that are not typically assessed for risk of bias. Cost results were converted to 2022 United States Dollars (USD). Further detail on SLR methodology can be found in the study protocol (PROSPERO CRD: 42022376557).
Results
Twenty-four studies were eligible for inclusion in the final review (Figure 1). Prospective observational (10) and economic analyses (7) were the predominant study designs, with comparatively fewer randomized controlled trials (6) and retrospective observational (1) studies. Most studies were conducted either in Europe (11) or North America (8), and sample sizes ranged from 87 patients to 1915 patients. Patient characteristics varied between studies with mean age ranging from 9.4 to 61.6 years, and existing medical conditions included cardiac, psoriatic, and rheumatologic disorders such as rheumatoid arthritis. Additional study and patient characteristics can be found in Tables 26,15-36 and 3. Full results for each study are detailed in Table 4,6,15-36 with summaries and important results described below.
PRISMA flow diagram.
Study Summary.
Study and Baseline Patient Characteristics.
Patient studies only (n = 3 studies reporting patient studies). Sample sizes consisting of health care professionals, syringes, or observations not considered.
SLR Results by Study.
Abbreviations: IQR, interquartile range; pADE, preventable adverse drug event; SLR, systematic literature review; TEAE, treatment emergent adverse event; CCU, critical care unit; CPM, conventional preparation method; PVC, peripheral venous catheters.
Clinical Outcomes
Preventable adverse events
Adverse events and administration errors were reported in 12 studies.15-26 Preparation and administration errors occurred more frequently in procedures utilizing traditionally prepared syringes (10.4%-73.6%) compared with prefilled syringes (1.4%-2.5%).17,23
A randomized simulation study identified that the most frequent error with traditionally prepared syringes (73.6% error rate, P < 0.001) was due to the lack of syringe labeling. 17 The single error reported for prefilled syringes in the same study (1.4% error rate) was related to a dose diluted into a prefilled syringe. In a prospective observational study, disinfection, dilution, and labeling errors were identified as the most frequent observed errors. Traditionally prepared syringes had a 10.4% observed error rate, while prefilled syringes had a lower rate of 2.5%. 23 The observed error rate was calculated as the total number of technique errors divided by the total number of opportunities for error. Furthermore, a greater proportion of traditionally prepared syringe observations contained errors (179/227, 79%) than ready-to-administer observations (22/102, 22%) (P < 0.001). In the same study, prefilled syringes and traditionally prepared syringes were compared with a third option marketed as Carpuject. The study showed a 77% proportion of errors associated with Carpuject. However, it is important to note that this may not represent the typical use of prefilled syringes in clinical practice. The design of the study included the possibility of Carpuject misuse, such as permitting the withdrawal of drugs from the cartridge using a needle. 23
In 2 cost-effectiveness models, pADEs were reported per 100 administrations. The first model showed that traditional vials had 1.1 pADEs, while prefilled syringes were associated with 0.275 pADEs.15,24 The pADEs were calculated using the probability of errors reported in the prospective observational study previously presented 23 and the probability of an error causing harm obtained from a retrospective study from 2012, which is not part of this current review. 37 Common types of medication for which these outcomes were assessed included morphine, atropine, and fentanyl. The second study was an economic model that derived pADEs rates from a United States study of perioperative medication errors, resulting in 1.39 pADEs for traditionally prepared syringes and 0.73 pADEs per 100 administrations for prefilled syringes. 24 The authors calculated pADEs for prefilled syringes by assuming that prefilled syringes introduction eliminates dosing and labeling errors (47.1% of all errors) and that all errors were equally likely to lead to a pADE from an observational study in 2016. 38
Sterility and contamination
Four studies reported on sterility outcomes in traditional and prefilled syringes.27-30 Syringe sterility was evaluated at 4 weeks, 8 weeks, 12 weeks, and 1 year across identified studies. There was no significant difference, as all studies reported zero cases of sterility being broken in either traditionally prepared syringes or prefilled syringes.
Economic Outcomes
Total cost
Economic outcomes were reported in 7 studies.5,6,15,16,22,24,31 Five analyses specifically reported hospital and health system-level costs and cost benefits.5,6,15,16,31 Those reporting on hospitals found that if 50% of traditional methods were replaced by prefilled syringes over $6 million could be saved.6,16 Studies examining health systems also showed that over $7 million could be saved in France with the adoption of prefilled syringes of atropine.5,15,31 Further details can be found in Table 4.5,6,15-36
Seven studies reported the results of an economic model designed to estimate the budget or cost impact of the use of prefilled syringes over traditional vials.5,6,15,16,22,24,31 Further details can be found in Table 4.5,6,15-36 A cost-minimization analysis evaluating annual costs in a general Dutch hospital estimated that the cost of wastage would be reduced by half, representing $63 895 when switching 50% of traditionally prepared syringes to prefilled syringes prepared by the hospital pharmacy, as each prefilled syringes would require no manipulation or operation prior to use. 6 The 50% switch value was selected to reflect that medicines presented in vials are not always commercially available as prefilled syringes. In addition, preparation of prefilled syringes in this scenario differed from the traditional good manufacturing practice (GMP)-filled method used by pharmaceutical companies.
This same analysis estimated that the annual cost of medication preparation errors would be reduced by half, representing $4 793 313 when switching 50% of traditional preparation methods via vial and syringe to prefilled syringes. 6 Annual costs due to bacteremia were also estimated to be lower when utilizing prefilled syringes, with traditional methods estimated to cost $3 137 258 annually compared with $1 585 118 in the scenario using 50% of prefilled syringes. The additional cost of prefilled syringes acquisition of $106 484 could be offset by the cost of medication errors, wastage, and contamination avoided, resulting in a total of $6 million savings for this Dutch hospital if 50% of traditionally prepared syringes were replaced by prefilled syringes. The noted limitations of this study include the use of data obtained from one hospital combined with data from literature studies, preferably systematic reviews, which may limit the generalizability of the model. However, even with 10% variation in the inputs, the results still showed cost savings when using prefilled syringes. 6 Another study estimated the cost of atropine administration in a hypothetical UK ICU, finding that switching to prefilled syringes would save $73 500 annually via reductions in pADEs. 24
A budget impact model also assessed the impact of switching from atropine in vials to prefilled syringes of atropine in French hospitals. 5 It was estimated that the additional cost $7 million for acquiring prefilled syringes could be offset by the cost savings from avoiding medication errors and wastage, resulting in a total of savings of $7 million for the French health care system. The authors of this study highlighted certain limitations, such as that inputs were based on data obtained from the literature and expert opinions. After applying 10% variation to these parameters, the results of the deterministic sensitivity analysis demonstrated that prefilled syringes remained a cost-savings option. An economic analysis of nurse resourcing for administration of noradrenaline in England estimated an 85% reduction of nurse resource using prefilled syringes, equivalent to a release of 176.3 whole time equivalents (WTEs) across England (109 and 67 WTEs for drug preparation and pump management, respectively). The additional investment for prefilled syringes acquisition costs represents a budget uplift of $4.1 million in England compared with traditional vials. The average nurse preparation time required for prefilled syringes was estimated by a survey of clinical experts, and the time to prepare syringes using traditional vials was sourced from an NHS report. The reliance on experts to estimate inputs may be a source of uncertainty and may not be generalizable to other health care systems. However, this finding may be conservative because the cost of medication preparation errors was not included in this study. 31 In a separate cost-analysis comparing flush costs of prefilled syringes to manual preparation for central venous catheter use, prefilled syringes were shown to reduce the cost per flush by $19.1, or 67%. 22
Modeled outcomes
In 4 studies, health resource utilization, such as wastage, were modeled as part of an economic analysis.15,16,24,31 One analysis of the consumption and administration of norepinephrine in United Kingdom (UK) ICUs estimated that 7.3 mg would be discarded daily due to sterility protocols (mandatory discard after 24 hours) when using traditionally prepared drug, whereas a ready-to-administer system was estimated to result in only 2.5 mg being discarded, even with the same sterility protocol. 31 This same study estimated that the total volume of norepinephrine consumed daily through administration to patients could be reduced by 25% (33.6 vs 25.2 mg) through utilization of a ready-to-administer program.
Health Resource Utilization Outcomes
Unused drug and wastage
Among the clinical outcomes assessed, 4 studies reported on drug wastage.20,31-33 Wastage rates ranging from 46.0% to 92.0% were observed among traditionally prepared syringes of ephedrine and atropine, respectively, compared with 0.0% to 15.3% wastage with prefilled syringes of ephedrine and metaraminol, respectively.32,33 Wastage results all pertained to full syringes being discarded due to expiry or hospital operating procedures, not residual volume remaining after drug administration. The lifetime of prefilled syringes (3 years if the blister is not opened) prepared by a pharmaceutical manufacturer limited wastage in a Canadian hospital. The study estimated 92% of daily prepared atropine syringes were wasted compared with 9% of prefilled syringes due to only one prefilled syringe prepared by error and wasted. 34
Time savings
Nine studies reported on time savings outcomes.16,17,19,24,25,31,34-36 Preparation times for a variety of procedures, including intravenous (IV) push medication, IV flush, intravitreal injection, vascular access, and intubation ranged from 64.2 to 497.5 seconds for traditional preparation methods,34,35 while use of prefilled syringes resulted in preparation times ranging from 28.7 (95% CI, 23.3-24.2) to 236 seconds (interquartile range [IQR], 210-270).17,36 In all 5 studies reporting procedure preparation time, prefilled syringes were time-saving compared with traditional methods, with difference in time saved ranging from 4.0 seconds for the preparation and administration of prefilled syringes with adrenaline during cardiopulmonary resuscitation to 338.0 seconds (5.6 minutes) for prefilled syringes used to reduce the time from decision to successful endotracheal intubation in a simulated pediatric emergency.34,36
Discussion
Wastage, staff inefficiencies, and human error in the administration of medication constitute a sizeable burden on patients, hospitals, and health care systems. Prefilled syringes offer a ready-to-use format that can simplify delivery of small-molecule drugs and help reduce waste, improve speed and quality of care, and mitigate opportunities for error compared with traditional methods of medication preparation. This SLR assessed recently published literature to shed light on the clinical, economic, and health resource utilization benefits of prefilled syringes use and reinforce emerging literature on the advantages of utilizing prefilled syringes.9,39 Overall, prefilled syringes were associated with favorable clinical and health resource utilization outcomes that translated into economic benefits for departments, hospitals, and health systems.
Clinical outcomes related to the use of prefilled syringes demonstrated several key advantages over traditional syringe preparation methods. First, prefilled syringes were associated with fewer preparation and administration errors, resulting in improved patient safety and overall quality of care. The comparatively lower estimated rate of pADEs (albeit based on one modeled analysis) with prefilled syringes highlights potential value in reduced adverse events that should be explored in future research. Second, although sterility outcomes were rarely reported in the literature, prefilled syringes were shown to be as safe and effective at maintaining sterility as traditional prepared syringes.
Health resource utilization outcomes related to the use of prefilled syringes demonstrated a reduction in drug wastage and preparation time, allowing for potential efficiency improvements. This is an important consideration for health care providers, as minimizing waste can contribute to drug cost containment and better health care sustainability. In addition, prefilled syringes offer time-saving benefits for health care providers, allowing quicker preparation of medication and better resources management which may lead to more time allocated to direct patient care.
Economic models that assessed medication costs of departments, hospitals, and health care systems estimated that the implementation and utilization of prefilled syringes may drive potential savings through reduced wastage, time savings, and decreased errors. Switching to prefilled syringes were projected to incur increased costs of procurement, but these additional costs are anticipated to be offset by savings in reduced wastage and pADEs. While the clinical trials measuring error rates and pADEs are limited and may report different magnitudes of effect, their results were in favor of prefilled syringes and the sensitivity analyses conducted in economic models demonstrated that prefilled syringes remained a cost-savings option.
Reduction of adverse drug events is a potential driver for reduced costs associated with prefilled syringes, as a single serious event can result in a hospital admission and several days of stay. The reduced number of preparation steps leads to reducing the risk of error and ultimately increasing savings due to fewer pADEs. While other errors can occur after preparation, results highlighted that prefilled formulates can minimize opportunity for mistakes due to stress, oversight, or negligence.
Relevance to Patient Care and Clinical Practice
This literature review adds new insights that reveal prefilled syringes, as a medication administration method, can potentially reduce pADEs and can also offer time and cost benefits based on more recent studies. 40 Transitioning to prefilled syringes for a proportion of medication preparation could also lead to reductions in medication wastage. This review suggests potential economic benefits to prefilled syringes utilization, as well, related to reduced staff time. Even if utilization of prefilled syringes does not directly translate into reduced numbers of nursing staff required on each shift, the time benefit gained by using prefilled syringes allows nursing staff to allocate more time to patient care activities. This, in turn, may ultimately result in improved patient care and outcomes. However, further research—including qualitative research to contextualize patient and clinical experiences—is recommended to better quantify and understand benefits and considerations related to care delivery, quality, and patient impact.
Limitations
This review has some limitations. Most studies identified were observational, which may lead to the potential for increased bias due to lack of participant randomization. Patient sample sizes were small across the studies included, limiting the representativity of the study population and thus the generalizability of findings. Given the array of outcomes queried, some outcomes, such as contamination, pADEs, and certain cost savings, were only reported in a handful of articles and could not be compared against or validated by other literature. In addition, because some studies utilized economic models to estimate benefits of prefilled syringes use, it is possible that results were overstated as assumptions were made on factors such as cost, error frequency, and staff time. Despite these limitations, the SLR was conducted in a systematic, rigorous manner in alignment with PRISMA-P guidelines and used independent reviewers to minimize bias. Future studies should examine the benefits of prefilled syringes by drug class, as departments that primarily administer different drug classes (ie, opioids, anesthesia, noradrenaline) may have varying levels of benefits.
Some of the studies were designed as simulation studies or conducted in one hospital only, limiting the generalizability of the results to all settings and countries because of the variability in nursing practices. However, all studies reported wastage improvements and time savings in favor of prefilled syringes. In addition, limited methodological detail on factors such as prefilled syringe acquisition costs in some of the economic studies makes it difficult to ascertain the validity of findings such as savings demonstrated. This review also did not find studies assessing drug interactions with the syringe, which can be an important consideration in choosing this method of administration. 41 Finally, more data are needed around the ecological impact of prefilled syringes, which could potentially be more favorable than traditional preparation methods given wastage minimization associated with prefilled syringes use.
Conclusion and Relevance
This SLR represents a detailed exploration of clinical and economic outcomes associated with the use of prefilled syringes compared with conventional drug preparation methods. The findings add new insights of potential prefilled syringe benefits, including a reduction in preventable adverse events, decreased drug wastage, and improved workflow efficiency. These may contribute to the expanded use of this medication administration modality to enhance patient safety and operational efficiencies in health care settings. However, further real-world research on clinical, economic, and ecological outcomes is needed in diverse settings of care and geographies to gain a deeper understanding of the utility and benefits of prefilled syringes. In addition, other factors should be further researched and considered when switching to prefilled syringes, such as stability, compatibility, and quality control of the product.
Supplemental Material
sj-docx-1-aop-10.1177_10600280231212890 – Supplemental material for Assessing the Clinical, Economic, and Health Resource Utilization Impacts of Prefilled Syringes Versus Conventional Medication Administration Methods: Results From a Systematic Literature Review
Supplemental material, sj-docx-1-aop-10.1177_10600280231212890 for Assessing the Clinical, Economic, and Health Resource Utilization Impacts of Prefilled Syringes Versus Conventional Medication Administration Methods: Results From a Systematic Literature Review by Dan Benhamou, Mia Weiss, Matthias Borms, Julia Lucaci, Haymen Girgis, Cecile Frolet, Wesley T. Baisley, Gio Shoushi, Kristen A. Cribbs and Manuel Wenk in Annals of Pharmacotherapy
Footnotes
Acknowledgements
The authors thank Alkemi LLC contributor Betsy J. Lahue, who provided strategic advisement, and BD contributors Eric Borrelli, who completed the risk of bias assessments and Marion Richard, who reviewed the manuscript.
Author Contributions
Availability of Data and Materials
Data analyzed during the current study are available from the corresponding author on reasonable request.
Consent for Publication
Not applicable.
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MW, MB, JL, HG, and CF are employees of Becton, Dickinson and Company. KAC, WTB, and GS were paid consultants to Becton, Dickinson and Company and study investigators. DB received fees for consulting and being speaker in conferences organized by Aguettant in the last 3 years.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Becton, Dickinson and Company.
Ethics Approval and Consent to Participate
Not applicable.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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