Published on in Vol 27 (2025)

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/65546, first published .
Digital Health Technology Interventions for Improving Medication Safety: Systematic Review of Economic Evaluations

Digital Health Technology Interventions for Improving Medication Safety: Systematic Review of Economic Evaluations

Digital Health Technology Interventions for Improving Medication Safety: Systematic Review of Economic Evaluations

Review

1Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia

2Centre of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, Indonesia

3School of Business & Management, Bandung Institute of Technology, Bandung, Indonesia

4Department of Mathematics, Universitas Padjadjaran, Sumedang, Indonesia

Corresponding Author:

Widya Norma Insani, PhD

Department of Pharmacology and Clinical Pharmacy

Universitas Padjadjaran

Jl Raya Bandung Sumedang KM 21, Jatinangor

Sumedang, 45363

Indonesia

Phone: 62 7796200

Email: widya.insani@unpad.ac.id


Background: Medication-related harm, including adverse drug events (ADEs) and medication errors, represents a significant iatrogenic burden in clinical care. Digital health technology (DHT) interventions can significantly enhance medication safety outcomes. Although the clinical effectiveness of DHT for medication safety has been relatively well studied, much less is known about the cost-effectiveness of these interventions.

Objective: This study aimed to systematically review the economic impact of DHT interventions on medication safety and examine methodological challenges to inform future research directions.

Methods: A systematic search was conducted across 3 major electronic databases (ie, PubMed, Scopus, and EBSCOhost). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. Two independent investigators conducted a full-text review after screening preliminary titles and abstracts. We adopted recommendations from the Panel on Cost-Effectiveness in Health and Medicine for data extraction. A narrative analysis was conducted to synthesize clinical and economic outcomes. The quality of reporting for the included studies was assessed using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines.

Results: We included 13 studies that assessed the cost-effectiveness (n=9, 69.2%), cost-benefit (n=3, 23.1%), and cost-utility (n=1, 7.7%) of DHT for medication safety. Of the included studies, more than half (n=7, 53.9%) evaluated a clinical decision support system (CDSS)/computerized provider order entry (CPOE), 4 (30.8%) examined automated medication-dispensing systems, and 2 (15.4%) focused on pharmacist-led outreach programs targeting health care professionals. In 12 (92.3% ) studies, DHT was either cost-effective or cost beneficial compared to standard care. On average, DHT interventions reduced ADEs by 37.12% (range 8.2%-66.5%) and medication errors by 54.38% (range 24%-83%). The key drivers of cost-effectiveness included reductions in outcomes, the proportion of errors resulting in ADEs, and implementation costs. Despite a significant upfront cost, DHT showed a return on investment within 3-4.25 years due to lower cost related with ADE treatment and improved workflow efficiency. In terms of reporting quality, the studies were classified as good (n=10, 76.9%) and moderate (n=3, 23.1%). Key methodological challenges included short follow-up periods, the absence of alert compliance tracking, the lack of ADE and error severity categorization, and omission of indirect costs.

Conclusions: DHT interventions are economically viable to improve medication safety, with a substantial reduction in ADEs and medication errors. Future studies should prioritize incorporating alert compliance tracking, ADE and error severity classification, and evaluation of indirect costs, thereby increasing clinical benefits and economic viability.

J Med Internet Res 2025;27:e65546

doi:10.2196/65546

Keywords



Medication-related harm, including adverse drug events (ADEs) and medication errors, represents a significant burden in clinical care [World Health Organization. Global burden of preventable medication-related harm in health care: a systematic review. World Health Organization. 2017. URL: https://www.who.int/publications/i/item/9789240088887 [accessed 2024-04-01] 1]. A previous systematic review showed that 3% of patients in various health care settings experience preventable medication-related harm worldwide, with a quarter classified as severe or potentially life threatening [Hodkinson A, Tyler N, Ashcroft DM, Keers RN, Khan K, Phipps D, et al. Preventable medication harm across health care settings: a systematic review and meta-analysis. BMC Med. Nov 06, 2020;18(1):313. [FREE Full text] [CrossRef] [Medline]2]. Unsafe medication practices can occur at various stages of the medication process, including prescribing errors, where nearly 50% of medication errors occur (eg, inappropriate drugs for age and condition, incorrect dosage, contraindication, and drug-drug interactions (DDIs) overlooked) [Velo GP, Minuz P. Medication errors: prescribing faults and prescription errors. Br J Clin Pharmacol. Jun 25, 2009;67(6):624-628. [FREE Full text] [CrossRef] [Medline]3,Wheeler AJ, Scahill S, Hopcroft D, Stapleton H. Reducing medication errors at transitions of care is everyone's business. Aust Prescr. Jun 01, 2018;41(3):73-77. [FREE Full text] [CrossRef] [Medline]4]; dispensing errors; administration errors; and inadequate monitoring (eg, hypokalemia due to inadequate renal and electrolyte monitoring among diuretic users) [Piazza G, Nguyen TN, Cios D, Labreche M, Hohlfelder B, Fanikos J, et al. Anticoagulation-associated adverse drug events. Am J Med. Dec 2011;124(12):1136-1142. [FREE Full text] [CrossRef] [Medline]5,Schepkens H, Vanholder R, Billiouw J, Lameire N. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med. Apr 15, 2001;110(6):438-441. [CrossRef] [Medline]6]. Additional costs associated with medication errors have been estimated at US $42 billion annually, indicating a significant burden of unsafe medication practices for patients and the health system [Aitken M. Advancing the Responsible Use of Medicines: Applying Levers for Change. Parsippany, NJ. IMS Institute for Healthcare Informatics; 2012. 7].

Digital health technology (DHT) applies information and communication technology to enhance health care outcomes [Rowlands D. What is digital health? Health Informatics Society of Australia. 2019. URL: https://www.hisa.org.au/wpcontent/uploads/2019/12/What_is_Digital_Health.pdf [accessed 2025-01-23] 8]. DHT interventions range from a clinical decision support system (CDSS)/computerized provider order entry (CPOE) or electronic prescribing, automated medication-dispensing systems, telemedicine, and mobile health (mHealth) apps to telephone or text message reminders [Afreen N, Padilla-Tolentino E, McGinnis B. Identifying potential high-risk medication errors using telepharmacy and a web-based survey tool. Innov Pharm. Feb 12, 2021;12(1):9. [FREE Full text] [CrossRef] [Medline]9-Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12]. DHT may assist in supporting clinical decisions and enhancing the monitoring of medication use [Food and Drug Administration. What Is Digital Health? Silver Spring, MD. Food and Drug Administration; 2020. 13,Stoumpos AI, Kitsios F, Talias MA. Digital transformation in healthcare: technology acceptance and its applications. Int J Environ Res Public Health. Feb 15, 2023;20(4):3407. [FREE Full text] [CrossRef] [Medline]14]. Several studies have shown that DHT may confer benefits by reducing ADEs and medication errors in both hospital and community settings [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15-Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17]. Previous systematic reviews have examined the clinical impact of DHT interventions (ie, CPOE) to improve medication safety [Ammenwerth E, Schnell-Inderst P, Machan C, Siebert U. The effect of electronic prescribing on medication errors and adverse drug events: a systematic review. J Am Med Inform Assoc. Sep 01, 2008;15(5):585-600. [CrossRef]18,Ranji SR, Rennke S, Wachter RM. Computerised provider order entry combined with clinical decision support systems to improve medication safety: a narrative review. BMJ Qual Saf. Sep 12, 2014;23(9):773-780. [CrossRef] [Medline]19], but none have examined the economic impact of such interventions.

Given the increasing application of DHT, there is an urgent need to determine the economic benefits of DHT to allow clinicians to decide whether to implement DHT strategies [Park T, Kim H, Song S, Griggs SK. Economic evaluation of pharmacist-led digital health interventions: a systematic review. Int J Environ Res Public Health. Sep 22, 2022;19(19):11996. [FREE Full text] [CrossRef] [Medline]20]. Although DHT interventions can potentially improve clinical outcomes, their additional expense for infrastructure, implementation, and maintenance may hinder their adoption compared to standard care [Clarke M, Fursse J, Brown-Connolly NE, Sharma U, Jones R. Evaluation of the National Health Service (NHS) direct pilot telehealth program: cost-effectiveness analysis. Telemed J E Health. Jan 2018;24(1):67-76. [CrossRef] [Medline]21,Lopez-Villegas A, Catalan-Matamoros D, Peiro S, Lappegard KT, Lopez-Liria R. Cost-utility analysis of telemonitoring versus conventional hospital-based follow-up of patients with pacemakers. The NORDLAND randomized clinical trial. PLoS One. Jan 29, 2020;15(1):e0226188. [FREE Full text] [CrossRef] [Medline]22]. This study aimed to systematically review the economic impact of DHT interventions on medication safety and examine the methodological challenges in these interventions. Such understanding can better inform resource allocation and policy decisions for strengthening health system capacity [Slawomirski L, Auraaen A, Klazinga NS. The economics of patient safety. Organisation for Economic Co-operation and Development. 2017. URL: https://www.oecd.org/en/publications/the-economics-of-patient-safety_5a9858cd-en.html [accessed 2025-01-23] 23].


Search Strategy

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guideline. A systematic search was performed across 3 major electronic databases (PubMed, Scopus, and EBSCOhost) to identify studies investigating economic evaluations of DHT to improve medication safety outcomes (ie, reduction in ADEs and medication errors). The search strategies included 3 categories of terms related to:

  • DHT interventions, defined as strategies that use information and communication technology to enhance health outcomes (ie, reduction in ADEs and medication errors). To ensure comprehensive coverage of all available evidence, we included a broad range of DHT interventions, including a CDSS/CPOE, electronic prescribing, telemedicine, telepharmacy, automated medication-dispensing systems, mHealth apps, and telephone or text message reminders. Comparators included paper-based prescribing, traditional floor stock storage, and standard pharmaceutical care.
  • Medication safety outcomes (ie, changes in the ADE and medication error rate). An ADE is defined as “an injury resulting from the use of a drug,” which includes harm resulting from either errors or medication-inherent effects [Bates DW, Boyle DL, Vliet MBV, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. Apr 1995;10(4):199-205. [CrossRef]24]. The term “medication error” refers to “any error in the process of prescribing, dispensing, or administering a drug, which may or may not result in harm” [Leape L. Preventing adverse drug events. Am J Health Syst Pharm. Feb 15, 1995;52(4):379-382. [CrossRef] [Medline]25]. A previous study showed that although medication errors are common, only around 1% result in actual harm or ADEs, which might be because these errors have little potential for injury or they are intercepted before an adverse outcome occurs [Bates DW, Boyle DL, Vliet MBV, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. Apr 1995;10(4):199-205. [CrossRef]24,Montesi G, Lechi A. Prevention of medication errors: detection and audit. Br J Clin Pharmacol. Jun 25, 2009;67(6):651-655. [FREE Full text] [CrossRef] [Medline]26].
  • Economic evaluations (ie, cost-benefit analysis [CBA], cost-effectiveness analysis [CEA], cost-utility analysis [CUA], and cost minimization analysis [CMA]).

Full details of the search strategy are provided in Table 1. An additional search of reference lists of relevant reviews and included studies was performed.

Table 1. Search strategy of DHTa interventions for medication safety.
Type of key termsSearch strategy
Terms related to DHT interventionsTelemedicine[MeSHb] OR telepharmacy[tiab] OR computerized provider order entry[tiab] OR computerized physician order entry[tiab] OR computer provider entry[tiab] OR clinical decision support[tiab] OR automated medication system[tiab] OR automated pharmacy system[tiab] OR bar coding[tiab] OR electronic medication order entry[tiab] OR electronic medication management system[tiab] OR electronic prescribing[tiab] OR ePrescribing OR electronic prescription[tiab] OR electronic medication administration records[tiab] OR electronic system*[tiab] OR automated dispensing[tiab] OR computerized reminder system[tiab] OR information technology[tiab] OR medication ordering entry[tiab] OR electronic medication ordering and administration system[tiab] OR remote consultation[MeSH] OR electronic consult*[tiab] OR digital technolog*[tiab] OR teleconsult*[tiab] OR mhealth[tiab] OR m-health[tiab] OR multimedia[tiab] OR virtual[tiab] OR mobile health[tiab] OR telemedicine[tiab] OR electronic health record[tiab] OR telehealth[tiab] OR telecare[tiab] OR telehealth care[tiab] OR mobile health intervention*[tiab] OR mobile applications[tiab] OR mobile telemedicine[tiab] OR mcare[tiab] OR m-care[tiab] OR mobile communication[tiab] OR mobile technolog*[tiab] OR multimedia technolog*[tiab] OR mobile devic*[tiab] OR app[tiab] OR apps[tiab] OR mobile app*[tiab] OR website*[tiab] OR internet consultation*[tiab] OR internet monitoring[tiab] OR video consultation*[tiab] OR video monitoring[tiab] OR telephone*[tiab] OR mobile phone*[tiab] OR smart phone*[tiab] OR smart-phone*[tiab] OR text messag*[tiab] OR text messaging[tiab] OR SMS[tiab] OR short messag*[tiab] OR multimedia messag*[tiab] OR multi-media messag*[tiab] OR website platform[tiab] OR web-based medication platform[tiab] OR web-based application[tiab] OR web-based tool[tiab] OR electronic health[tiab] OR ehealth[tiab] OR e-health[tiab]
Terms related to medication safety outcomesDrug-related side effects and adverse reactions [MeSH] OR adverse drug reaction*[tiab] OR adverse drug event*[tiab] OR drug related problem*[tiab] OR medication related problem[tiab] OR drug therapy problem*[tiab] OR drug safety[tiab] OR medication safety[tiab] OR medication error*[tiab] OR prescribing error*[tiab] OR prescription error*[tiab] OR dispensing error*[tiab] OR administration error*[tiab] OR inappropriate prescribing[tiab] OR inappropriate medication*[tiab] OR drug complication*[tiab]
Terms related to economic evaluationsCost and cost analysis[MeSH] OR cost-benefit analysis[MeSH] OR cost-effectiveness[tiab] OR cost utility[tiab] OR cost minimi*[tiab] OR economic evaluation[tiab] OR economic analysis[tiab]

aDHT: digital health technology.

bMeSH: Medical Subject Headings.

Inclusion and Exclusion Criteria

We included studies that reported health economic evaluations of DHT to improve medication safety outcomes (ie, ADEs and medication errors) compared to standard care. Detailed information related to inclusion criteria is provided in Table 2. We excluded studies where the intervention did not include DHT, studies that did not report medication safety outcomes, studies without full economic evaluation, non-English studies, conference abstracts, and editorials.

Table 2. PICOa framework and inclusion criteria of the study.
Framework itemInclusion criteria
Population/problemPatients receiving medication at any point of care, including in hospital and community settings
InterventionAny DHTb intervention, including:
  • CDSSc/CPOEd
  • Automated medication-dispensing system
  • Telepharmacy, telemedicine
  • mHealthe app
  • Other
ComparatorStandard care (eg, paper-based prescribing, traditional floor stock storage)
OutcomeReduction in ADEsf and medication errors
Study typeA full economic evaluation of DHT to improve medication safety categorized as CBAg, CEAh, CUAi, and CMAj

aPICO: population/problem, intervention, comparator, outcome.

bDHT: digital health technology.

cCDSS: clinical decision support system.

dCPOE: computerized provider order entry.

emHealth: mobile health.

fADE: adverse drug event.

gCBA: cost-benefit analysis.

hCEA: cost-effectiveness analysis.

iCUA: cost-utility analysis.

jCMA: cost minimization analysis.

Screening and Data Extraction

The database-screening results were exported to the Mendeley reference manager library and examined for duplicates. Two investigators (authors WNI and NZ) independently conducted a full-text review after screening the preliminary titles and abstracts. Any discrepancies between the 2 reviewers were resolved through discussion. We adopted recommendations from the Panel on Cost-Effectiveness in Health and Medicine for data extraction. Data extracted included (1) study characteristics; (2) clinical and economic outcomes, including the incremental cost-effectiveness ratio (ICER), the cost-benefit ratio (CBR), and the return on investment (ROI); (3) cost components; (4) methodological challenges; and (5) quality of reporting. All monetary values were converted to 2024 US dollar values using the Campbell and Cochrane Economics Methods Group–Evidence for Policy & Practice Information Centre Cost Converter [CCEMG: EPPI-Centre cost converter. EPPI Centre. 2022. URL: https://eppi.ioe.ac.uk/costconversion [accessed 2025-01-23] 27].

Quality of Reporting

Reporting quality was assessed using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) 2022 checklist. The checklist included 28 items, classified into 6 categories: (1) title and abstract, (2) introduction, (3) methods (including choice of model, health outcomes, and measurement of effectiveness), (4) results, (5) discussion, and (6) others. Based on the reporting quality, the included studies were categorized as excellent (score 100%), good (score 75%-99%), moderate (score 50%-74%), and low (score ≤49%) [Zakiyah N, van Asselt ADI, Roijmans F, Postma MJ. Economic evaluation of family planning interventions in low and middle income countries: a systematic review. PLoS One. Dec 19, 2016;11(12):e0168447. [FREE Full text] [CrossRef] [Medline]28].


Study Selection

A total of 408 citations were retrieved from the electronic databases. After removing duplicates, 355 (87%) papers remained for evaluation based on titles and abstracts, yielding 49 (13.8%) records eligible for full-text assessment. A total of 13 (26.5%) economic evaluation studies [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29-Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37] were finally included in this systematic review. Most of the studies included CEA (n=9, 69.2%) [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29-Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34], followed by CBA (n=3, 23.1%) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36], and CUA (n=1, 7.7%) [Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. The included studies were predominantly conducted in hospital inpatient settings (n=10, 76.9%) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30-Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. The study selection flowchart based on PRISMA guidelines is provided in Figure 1.

Figure 1. PRISMA flowchart of study selection. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Overview of Key Characteristics

The most frequently implemented DHT intervention was the CDSS/CPOE or electronic medication record system. This intervention typically replaced traditional paper-based prescribing, with a safety alerts feature to assist clinicians in making informed decisions during the prescribing process [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33-Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]. A wide range of features were used in the included studies, ranging from basic DDI to the addition of medication administration tracking and various alerts, including pregnancy contraindications, allergy checks, dosage checks, therapeutic duplications, and potentially inappropriate medication (PIM) usage in vulnerable populations at increased risk of ADEs [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33-Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]. One study [Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30] compared a structured pharmacist medication review supported by a CDSS with a review conducted without CDSS support for older hospitalized patients. The intervention included medication reconciliation and personalized pharmaceutical care (Table 3).

Of the 13 studies, 4 (30.8%) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36] showed that the implementation of automated medication-dispensing systems has been increasingly used to reduce dispensing and administration errors, enhance workflow efficiency, and improve stock inventory tracking. These systems typically incorporated automated individual unit-dose dispensing, which ensured precise medication packaging tailored to patient-specific prescriptions, unlike manual systems where nurses prepare doses manually [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. The systems were often integrated with barcode scanning technology, either at the hospital pharmacy or at the patient bedside level, enabling verification of both the medication and the patient’s identity to prevent administration errors [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32]. Additional functionalities included structured drug storage and controlled access (eg, automated dispensing cabinets [ADCs] and medicine carousel systems with rotating shelves or bins to minimize the time spent searching for medications and medication selection errors) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. One intervention also improved inventory management by providing automated real-time stock monitoring [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10]. Furthermore, some systems were linked with electronic medication administration records and other CDSS tools, allowing better coordination between dispensing and prescribing processes [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36].

Table 3. Overview of key characteristics of the 13 included studies.
AuthorCountryDHTa typeTarget populationSample sizeType of studyTime horizon
Vermeulen et al [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12]The NetherlandsCDSSb/CPOEcPatients admitted to the internal medicine, gastroenterology, or geriatric ward1195CEAdAdmission to discharge
Westbrook et al [Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33]AustraliaCDSS/CPOEPatients admitted to the cardiology ward1202CEA15 years
Wu et al [Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34]CanadaCDSS/CPOEPatients admitted to all wards74,351CEA10 years
Avery et al [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15]United KingdomIT-based pharmacist outreachTargeted patients based on conditions and medications in general practices480,942CEA6 months
Berdot et al [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10]FranceAutomated medication dispendingPatients admitted to all wards70,421CBAe1 year
Forrester et al [Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29]United StatesCDSS/CPOEPatients in multidisciplinary outpatient clinics10,080CEA5 years
Elliot et al [Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]United KingdomIT-based pharmacist outreachTargeted patients based on conditions and medications in general practices480,942CUAf6 months
Gallagher et al [Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30]IrelandCDSS and pharmacist reviewOlder hospitalized patients737CEAAdmission to discharge or 10-day follow-up
Li et al [Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]ChinaCDSS/CPOEInpatients and outpatients620,000CBA6 years
Maviglia et al [Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]United StatesBarcode dispensingPatients admitted to all wards175,000CBA5 years
Nuckols et al [Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17]United StatesCPOE/CDSSPatients admitted to all wards4891gCEA10 years
Risør et al [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31]DenmarkAutomated medication dispensingPatients admitted to the hematological ward1336CEA6 months
Risør et al [Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32]DenmarkAutomated medication dispensingPatients admitted to acute wards90,000hCEA6 months

aDHT: digital health technology.

bCDSS: clinical decision support system.

cCPOE: computerized provider order entry.

dCEA: cost-effectiveness analysis.

eCBA: cost-benefit analysis.

fCUA: cost-utility analysis.

gNumber of acute care hospitals in the United States.

hTotal number of doses.

A technology-based pharmacist outreach was implemented in 2 (15.4%) studies [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37], involving pharmacists engaging directly with other health care professionals to target specific high-risk prescribing errors, such as prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) without proton pump inhibitors (PPIs) for patients with a history of peptic ulcers, beta-blockers for patients with asthma, and angiotensin-converting enzyme (ACE) inhibitors or diuretics without proper monitoring of renal function and electrolytes. The interventions involved a CDSS-supported feedback system and pharmacist educational outreach for general practice staff. This intervention model extended beyond simple error reporting by providing pharmacist-intensive support and guidance to other health care professionals.

Clinical Effectiveness Estimates

The DHT interventions were effective in reducing ADEs, with an average reported effectiveness of 37.12% (range 8.2%-66.5%) across the included studies (

Multimedia Appendix 2

Clinical and economic outcomes of the included studies.

DOCX File , 27 KBMultimedia Appendix 2 and Table 4) [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]. Medication errors reduced by an average of 54.38% (range 24%-83%) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31-Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. The variability in the effectiveness of DHT in reducing ADEs and medication errors can be influenced by differences in DHT features and the target population. A comprehensive CDSS/CPOE with both prescription entry and administration tracking resulted in greater reduction in ADEs compared to a CDSS/CPOE with only basic alerts [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34]. Nevertheless, none of the studies provided data on alert compliance tracking by health care professionals. Higher effectiveness was also observed in DHT interventions targeting high-risk populations, such as older and pediatric hospitalized patients. These populations are more prone to ADEs and medication errors resulting from comorbidities, concomitant medications, and differences in physiological characteristics. Consequently, interventions targeting these populations showed greater absolute reductions in ADEs and medication errors compared to interventions targeting lower-risk populations, as the elevated baseline risk provides more room for improvement [Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30].

Table 4. Examples of ADEsa and medication errors assessed in the included studies.
Safety outcomesExamplesReduction (%), mean (range)
ADEs
  • Dyspepsia associated with NSAIDsb, antiplatelets, and corticosteroids use
  • Severe hypotension resulting from ACEc inhibitors in patients with volume depletion
  • Acute kidney injury caused by NSAIDs prescribed without proper renal monitoring
  • Hyperkalemia due to the concurrent use of ACE inhibitors and potassium-sparing diuretics
  • Bleeding complications caused by an inappropriate dose of anticoagulants
  • Hypoglycemia resulting from insulin overdose
  • Bradycardia from incorrect beta-blocker dispensing
  • Falls and fractures caused by benzodiazepine use in older patients
  • Renal toxicity from aminoglycosides prescribed without dose adjustment for kidney function
  • Hypotension and syncope caused by inappropriate antihypertensive drug combinations
  • Cardiac arrhythmia caused by QT-prolonging drug combinations
  • Severe allergic reactions from failure to recognize and document allergies
37.12 (8.20-66.50)
Medication errors
  • Incorrect drug dosing due to incorrect weight-based calculation and transcription error
  • Failure to adjust medication doses for patients with renal impairment
  • NSAIDs without PPIsd in patients with ulcer history
  • Beta-blockers prescribed to patients with asthma
  • Dispensing the incorrect medication, strength, or dosage form
  • Errors related to supply failure or expired drugs
  • Monitoring errors, such as patients on ACE inhibitors or diuretics without renal and electrolyte monitoring in the past 15 months, patients on warfarin without a recorded International Normalized Ratio (INR) check in the past 12 weeks, patients on methotrexate without a full blood count or liver function test in the past 3 months
54.38 (24.00-83.00)

aADE: adverse drug event.

bNSAID: nonsteroidal anti-inflammatory drug.

cACE: angiotensin-converting enzyme.

dPPI: proton pump inhibitor.

Cost-Effectiveness Estimates

CDSS/CPOE Intervention

Implementation of a CDSS/CPOE to replace paper-based prescribing was associated with an average cost ranging from US $25.64 to $81.36 per patient, depending on the complexity and features of the system. The key cost components for a CDSS/CPOE included initial investments in hardware and software, licensing fees, staff training, ongoing system maintenance, and periodic updates to ensure compatibility with clinical workflows (Table 5) [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33-Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]. The implementation cost of a CDSS/CPOE depends on the hospital size, influenced by the need for more extensive hardware infrastructure and software to support a higher number of workstations, higher provider and patient volume, and more comprehensive clinical decision support rules to support various specialties [Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17]. Most studies evaluating a CDSS/CPOE reported the interventions as cost-effective from perspectives of societal, hospital, and health care systems, with 3 (23.1%) studies [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33] identifying cost-saving results. Only 1 (7.7%) study showed an exceptionally high ICER per ADE prevented without stating a willingness-to-pay (WTP) threshold, highlighting that more data on the effectiveness of CPOE in reducing ADEs are needed [Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34]. This study was conducted in 2006; therefore, the data on effectiveness may not reflect the most current findings, as presented in more recent studies [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. Although the development of an electronic medical record system with a CDSS requires an initial high investment, 1 (7.7%) study [Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35] showed that it yields a positive cost-benefit ratio of 1.45, indicating that every US $1 spent generates US $1.45 in benefits, with the ROI achieved within 3 years, driven by a 40% reduction in ADEs as additional treatments and hospitalizations due to ADEs reduced and efficiency improved from transitioning to electronic systems [Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35].

Table 5. Cost components associated with the DHTa interventions included in this review.
AuthorDHT typeCurrency, yearCost componentsDiscount rate (%)
Vermeulen et al [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12]CDSSb/CPOEcEuro, 2009
  • Software, hardware, and maintenance specific to the CDSS/CPOE
  • Costs for personnel involved in setting up and maintaining the system
  • Maintenance and operational costs: ongoing expenses for system updates and operational requirements
Not reported (follow-up period did not exceed 1 year)
Westbrook et al [Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33]CDSS/CPOEAU $, 2012-2013
  • Software license fees, infrastructure upgrades, and equipment specific to the electronic medication management system
  • Personnel training and configuration
  • Ongoing operating costs: annual software licensing fees, routine system maintenance, and regular training sessions for personnel
5
Wu et al [Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34]CDSS/CPOEUS $, 2007
  • Software and hardware setup
  • System configuration and testing
  • Training sessions for doctors, nurses, and support staff on using the new electronic system
  • Ongoing operational and maintenance costs: software updates and maintenance, licensing fees, and periodic staff training
  • Workload costs (considered in sensitivity analysis)
5
Avery et al [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15]IT-based pharmacist outreachUK pound sterling, 2012
  • Report generation
  • Pharmacist training
  • Error management activities, including review of patient medical records, consultations with general practitioners, patient follow-up (eg, patient counselling and medication adjustment, if needed), and training for general practice staff by pharmacists
Not reported (follow-up period did not exceed 1 year)
Berdot et al [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10]Automated medication-dispensing systemEuro, 2015
  • Purchase of dispensing units, including software and licenses
  • Immobilized drug stock
  • Annual maintenance
  • Labor costs: pharmacy technician wages for ADCd-related tasks
Not reported
Forrester et al [Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29]CDSS/CPOEUS $, 2010
  • Hardware, software, and system setup
  • Administrative costs: prescription processing, including chart pulls and queuing
  • Incentives: financial incentives related to meaningful use and pay-for-performance criteria
  • Maintenance costs
  • Personnel costs for implementation, training, and support
3
Elliot et al [Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]IT-based pharmacist outreachUK pound sterling, 2012
  • Report generation
  • Pharmacist training
  • Error management activities, including review of patient medical records, consultations with general practitioners, patient follow-up (eg, patient counselling and medication adjustment, if needed0, and training for general practice staff by pharmacists
3.5
Gallagher et al [Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30]CDSS and pharmacist reviewEuro, 2012
  • Pharmacist time and training: cost of pharmacists applying structured medication reviews and the CDSS
  • Health care staff review time: physician and nurse time for reviewing care plans
  • Hospital inpatient day: cost of inpatient care per day
  • Software and training costs
Not reported (follow-up period did not exceed 1 year)
Li et al [Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]CDSS/CPOEUS $, 2009
  • Hardware and software costs
  • Implementation costs: workflow setup, training, and transition
  • Maintenance costs: ongoing system support and utilities
10
Maviglia et al [Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]Barcode-dispensing systemUS $, 2009
  • Planning cost: workflow redesign and stakeholder engagement
  • Software development: linking the barcode system with the existing CPOE system, medication inventory, dose verification tracking, interface design, etc
  • Equipment purchase and infrastructure changes
  • Training cost
3
Nuckols et al [Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17]CDSS/CPOEUS $, 2012
  • Implementation cost: hardware, software, training, and technical support
  • Provider workflow cost
3
Risor et al [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31]Automated medication-dispensing systemEuro, 2017
  • System integration: development of interfaces between electronic medication administration records, scanners, and the barcode-scanning system
  • Equipment purchase: automated medication-dispensing machine and barcode-scanning devices
  • Operational costs: cost of dose packaging, pharmaceutical services for prescription checks, and additional labor costs
  • Training cost: training for nurses and pharmacy staff on AMSe processes
Not reported (follow-up period did not exceed one year)
Risor et al [Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32]Automated medication-dispensing systemEuro, 2018
  • System implementation: establishment of electronic medication administration records tailored to AMS types
  • Equipment purchase: automated medication-dispensing machines, scanners, and ADCs (complex automated medication system [CAMS] only)
  • Operational costs: maintenance costs, dose bag handling, and additional pharmacy labor for prescription checks (only for patient-specific automated medication system [PSAMS] and CAMS)
  • Training cost: education programs tailored to the AMS complexity used in each ward
Not reported (follow-up period did not exceed one year)

aDHT: digital health technology.

bCDSS: clinical decision support system.

cCPOE: computerized provider order entry.

dADC: automated dispensing cabinet.

eAMS: automated medication system.

Automated Medication-Dispensing System

Implementation of automated medication-dispensing systems to replace traditional floor stock systems was cost-effective and beneficial, with the ICER ranging from US $0.33 to $62.00 per medication error avoided [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. Key cost components for an automated medication-dispensing system included purchase of dispensing cabinets or medicine carousel systems with rotating shelves or bins, equipment for the repackaging center, software development, a barcode scanner, labor for restocking and packaging, training expenses, and system integration with the existing CPOE and pharmacy system. A reported net benefit of US $5,379,938.17 was achieved over 5 years, with the ROI attained within 4.25 years after initiation [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. The key drivers of the cost-effectiveness included handling costs and differences in the rates and types of medication errors [Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. Different types of dispensing errors have varying cost consequences; for example, the administration of an incorrect drug, dosage, or strength can have more severe consequences than procedural or administrative errors, which may potentially but not necessarily result in actual harm [Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32].

IT-Based Pharmacist Outreach

The implementation of a pharmacist-led DHT intervention was cost-effective in reducing clinically significant prescribing and monitoring errors in primary care, with an ICER of US $129.8 per medication error prevented and US $7788 per quality-adjusted life year (QALY) per practice [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. In addition, this intervention not only improved health outcomes (ie, additional QALYs) but also reduced overall costs compared to usual care, indicating its potential for cost savings [Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. Key cost components included pharmacist training, the time spent reviewing patient records and consulting with general practitioners (GPs), report generation from the CDSS, facilitation of practice meetings, patient follow-up, and system integration with the existing IT infrastructure. The number of patients per general practice was a key driver of cost-effectiveness in this intervention. In larger practices, intervention costs (eg, pharmacist training and CDSS report generation) are distributed across a broader patient base. In addition, the targeted nature of this intervention, which addressed specific prescribing errors (ie, NSAIDs without PPIs, beta-blockers for asthma, and monitoring errors) increased the efficiency and impact of pharmacists’ and GPs’ time in practices with higher patient volumes due to economies of scale [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37,Bernet PM, Singh S. Economies of scale in the production of public health services: an analysis of local health districts in Florida. Am J Public Health. Apr 2015;105(S2):S260-S267. [CrossRef]38].

Methodological Characteristics and Challenges in the Included Studies

Of the 13 studies 6 (46.2%) [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35] used a quasi-experimental design (ie, before-after and interrupted-time-series approaches, with multiple data points tracking ADEs and medication errors before and after DHT initiation). A decision analytic model was used in 3 (23.1%) studies [Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35], focusing on short-term, event-specific analysis, while a Markov model was used in 1 (7.7%) study [Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. Randomized controlled trial (RCT)–based evaluation was used in 2 (15.4%) studies [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30]. Challenges related to methodological aspects of evaluating DHT interventions for medication safety are presented in Table 6. Methodological challenges included short follow-up times, the absence of CDSS alert compliance tracking, a lack of ADE severity classification, and the omission of indirect costs (eg, productivity loss and caregiver time).

Table 6. Methodological challenges in DHTa intervention evaluation for medication safety.
DHT type and methodological issuesDescription
CDSSb/CPOEc

Study design
  • The short-term duration of the study (hospital stay until discharge or 10-day follow-up) did not capture the medium- or long-term impact of the intervention [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30].
  • Studies were not able to track whether or how many CDSS alerts were acknowledged and acted upon by health care professionals, limiting accurate assessment of DHT’s effectiveness [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33-Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35].
  • There was no standard care comparator. Before-after designs may not fully account for external factors influencing the observed trend [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35]. The use of a parallel control group for direct comparison could help mitigate confounding effects.

Cost data
  • Studies included a societal perspective but lacked data on indirect patient costs (eg, productivity loss, caregiver time) [Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17].

Clinical data
  • There was a lack of detailed ADEd severity classification, which may introduce variability in assessing ADE consequences and the benefits of the intervention [Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33].
  • Few studies assessed direct patient-centered outcomes (eg, hospital readmissions, QALYe) [Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17].
Automated medication-dispensing system

Study design
  • Studies did not analyze whether identified dispensing errors were tracked or immediately corrected (real-time monitoring), relying on retrospective analysis [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36].
  • Studies were conducted only in hospital settings, limiting generalizability to different settings.

Cost data
  • Studies did not explore how saved handling time could be reallocated to other productive tasks (ie, opportunity cost).

Clinical data
  • Studies focused on refill errors and urgent deliveries but did not systematically track errors or discrepancies between prescription and dispensing records [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10].
Pharmacist-led IT intervention

Study design
  • Studies focused on specific high-risk prescribing and monitoring errors but did not directly assess the proportion of errors leading to ADEs [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37].

aDHT: digital health technology.

bCDSS: clinical decision support system.

cCPOE: computerized provider order entry.

dADE: adverse drug event.

eQALY: quality-adjusted life year.

Quality of Reporting

Based on the quality assessment using the CHEERS checklist, most of the included studies (n=10, 76.92%) [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Nuckols TK, Asch SM, Patel V, Keeler E, Anderson L, Buntin MB, et al. Implementing computerized provider order entry in acute care hospitals in the United States could generate substantial savings to society. Jt Comm J Qual Patient Saf. Aug 2015;41(8):341-350. [FREE Full text] [CrossRef] [Medline]17,Forrester SH, Hepp Z, Roth JA, Wirtz HS, Devine EB. Cost-effectiveness of a computerized provider order entry system in improving medication safety ambulatory care. Value Health. Jun 2014;17(4):340-349. [FREE Full text] [CrossRef] [Medline]29-Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37] were rated as good, and the remaining 3 (23.1%) studies [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34,Li K, Naganawa S, Wang K, Li P, Kato K, Li X, et al. Study of the cost-benefit analysis of electronic medical record systems in general hospital in China. J Med Syst. Oct 3, 2012;36(5):3283-3291. [CrossRef] [Medline]35] were rated as moderate. Adherence to the checklist items varied across the section. Most studies did not report any approach to engagement with patients in the study design and results, except for the RCT-based study [Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30]. The rationale for selecting the model was inadequately reported in over a third of the studies, indicating issues in validating the selected methodology [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. All studies reported how to measure ADEs and medication errors; however, the valuation of these safety outcomes was not reported in some studies [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Westbrook J, Gospodarevskaya E, Li L, Richardson K, Roffe D, Heywood M, et al. Cost-effectiveness analysis of a hospital electronic medication management system. J Am Med Inform Assoc. Jul 2015;22(4):784-793. [FREE Full text] [CrossRef] [Medline]33]. The components of the outcomes included costs related to additional treatments and hospital stays due to the occurrence of ADEs and medication errors. Although most studies conducted sensitivity analysis to assess the robustness of the findings, only 1 (7.7%) study [Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32] assessed the heterogeneity of the outcomes based on different types of automated medication-dispensing systems. Most studies only focused on aggregated data without exploring subgroup differences, such as variations within patient populations, hospital wards, or intervention types.


Principal Findings

This is the first systematic review that assessed the economic evaluations of DHT interventions to improve medication safety outcomes. More than half of the studies (n=7, 53.9%) focused on a CDSS/CPOE, less than a third (n=4, 30.8%) on automated medication-dispensing systems, and the remaining (n=2, 15.4%) on pharmacist-led outreach programs targeting health care professionals. On average, DHT interventions reduced ADEs by 37.12% and medication errors by 54.38%. In 92.3% (12/13) of the included studies, the DHT was either cost-effective or cost beneficial compared to standard care. Despite a significant upfront cost, DHT showed an ROI within 3-4.25 years. Key methodological challenges included short follow-up periods, a lack of ADE severity categorization, the absence of alert compliance tracking, and the omission of indirect costs.

A CDSS/CPOE has been increasingly used to support clinicians in making informed decisions by providing recommendations based on patient data and clinical guidelines [Sutton RT, Pincock D, Baumgart DC, Sadowski DC, Fedorak RN, Kroeker KI. An overview of clinical decision support systems: benefits, risks, and strategies for success. NPJ Digit Med. Feb 06, 2020;3(1):17. [FREE Full text] [CrossRef] [Medline]39]. Nevertheless, the effectiveness of a CDSS is often compromised by alert fatigue, which occurs when clinicians override a large number of potentially irrelevant drug safety alerts (eg, drug interactions that are not clinically significant, flagging dosages outside the standard guideline when the prescribed dosage is appropriate for the patient condition) [Acheampong F, Anto B, Koffuor G. Medication safety strategies in hospitals--a systematic review. Int J Risk Saf Med. 2014;26(3):117-131. [CrossRef]40-van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc. Mar 01, 2006;13(2):138-147. [CrossRef]42]. A previous study showed that alert fatigue might be reduced by using a CDSS/CPOE with interactive features, such as incorporating tiered safety alerts with varying priority levels, offering action plans for clinicians (eg, dose reduction), and requiring clinicians to justify overriding an alert [Hussain M, Reynolds T, Zheng K. Medication safety alert fatigue may be reduced via interaction design and clinical role tailoring: a systematic review. J Am Med Inform Assoc. Oct 01, 2019;26(10):1141-1149. [FREE Full text] [CrossRef] [Medline]41]. In our review, none of the studies tracked CDSS/CPOE alert compliance, which may influence their effectiveness. A previous study showed drug allergy alerts had the highest compliance [Naeem A, Alwadie A, Alshehri A, Alharbi L, Nawaz M, AlHadidi R, et al. The overriding of computerized physician order entry (CPOE) drug safety alerts fired by the clinical decision support (CDS) tool: evaluation of appropriate responses and alert fatigue solutions. Cureus. Nov 2022;14(11):e31542. [FREE Full text] [CrossRef] [Medline]43]. Further DHT evaluation studies should investigate how alert compliance affects the outcomes to ensure optimal utility of DHT.

In addition, tailoring clinical roles within a CDSS can also enhance alert acceptance [Joosten H, Drion I, Boogerd KJ, van der Pijl EV, Slingerland RJ, Slaets JPJ, et al. Optimising drug prescribing and dispensing in subjects at risk for drug errors due to renal impairment: improving drug safety in primary healthcare by low eGFR alerts. BMJ Open. Jan 24, 2013;3(1):e002068. [FREE Full text] [CrossRef] [Medline]44-Smith T, Philmon CL, Johnson GD, Ward WS, Rivers LL, Williamson SA, et al. Antimicrobial stewardship in a community hospital: attacking the more difficult problems. Hosp Pharm. Oct 01, 2014;49(9):839-846. [FREE Full text] [CrossRef] [Medline]46]. A pharmacist-mediated CDSS has improved prescriber acceptance by filtering irrelevant advice and providing actionable drug safety recommendations [Joosten H, Drion I, Boogerd KJ, van der Pijl EV, Slingerland RJ, Slaets JPJ, et al. Optimising drug prescribing and dispensing in subjects at risk for drug errors due to renal impairment: improving drug safety in primary healthcare by low eGFR alerts. BMJ Open. Jan 24, 2013;3(1):e002068. [FREE Full text] [CrossRef] [Medline]44]. This approach leverages pharmacists’ expertise related to medication to support the decision-making process and reduce alert fatigue among prescribers [Armando LG, Miglio G, de Cosmo P, Cena C. Clinical decision support systems to improve drug prescription and therapy optimisation in clinical practice: a scoping review. BMJ Health Care Inform. May 02, 2023;30(1):e100683. [FREE Full text] [CrossRef] [Medline]47-Jokanovic N, Tan EC, Sudhakaran S, Kirkpatrick CM, Dooley MJ, Ryan-Atwood TE, et al. Pharmacist-led medication review in community settings: an overview of systematic reviews. Res Social Adm Pharm. Jul 2017;13(4):661-685. [CrossRef] [Medline]49]. Several included studies combined a CDSS with pharmacist-led interventions, such as structured medication review and targeted training for health care professionals for error correction, highlighting the central role of pharmacists in medication safety [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Gallagher J, O'Sullivan D, McCarthy S, Gillespie P, Woods N, O'Mahony D, et al. Structured pharmacist review of medication in older hospitalised patients: a cost-effectiveness analysis. Drugs Aging. Apr 9, 2016;33(4):285-294. [CrossRef] [Medline]30,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37].

Advancements in CDSSs/CPOE have significantly reduced prescribing errors, but administration errors, such as administering the wrong dose, using the incorrect route of administration, and failing to administer a scheduled dose, still present substantial room for improvement [Devine E, Hansen R, Wilson-Norton J, Lawless N, Fisk A, Blough D, et al. The impact of computerized provider order entry on medication errors in a multispecialty group practice. J Am Med Inform Assoc. 2010;17(1):78-84. [CrossRef]50]. This review found that a CDSS/CPOE with integrated prescription entry and administration tracking that address prescribing errors, while also monitoring and mitigating administration errors, achieves a greater reduction in ADEs compared to systems with basic features [Vermeulen K, van Doormaal J, Zaal R, Mol P, Lenderink A, Haaijer-Ruskamp F, et al. Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients. Int J Med Inform. Aug 2014;83(8):572-580. [CrossRef] [Medline]12,Wu RC, Laporte A, Ungar WJ. Cost-effectiveness of an electronic medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract. Jun 18, 2007;13(3):440-448. [CrossRef] [Medline]34]. The development and implementation of more comprehensive systems that target all stages of medication management, including administration, are essential to reduce medication errors and ADEs.

Different types of automated medication-dispensing systems were used in the included studies. Several factors need to be considered when selecting an automated medication-dispensing system, including the volume of prescriptions and types of medication the device can handle (eg, oral tablets, liquid medications, injectables), integration with the existing information technology system, and the presence of an error-checking mechanism [Zheng WY, Lichtner V, Van Dort BA, Baysari MT. The impact of introducing automated dispensing cabinets, barcode medication administration, and closed-loop electronic medication management systems on work processes and safety of controlled medications in hospitals: a systematic review. Res Social Adm Pharm. May 2021;17(5):832-841. [FREE Full text] [CrossRef] [Medline]51,Williams V, Haumba S, Ngwenya-Ngcamphalala F, Mafukidze A, Musarapasi N, Byarugaba H, et al. Implementation of the automated medication dispensing system-early lessons from Eswatini. Int J Public Health. Oct 12, 2023;68:1606185. [FREE Full text] [CrossRef] [Medline]52]. Almaki et al [Almalki A, Jambi A, Elbehiry B, Albuti H. Improving inpatient medication dispensing with an automated system. Glob J Qual Saf Healthc. 2023;6(4):117-125. [CrossRef]53] and Tsao et al [Tsao NW, Lo C, Babich M, Shah K, Bansback NJ. Decentralized automated dispensing devices: systematic review of clinical and economic impacts in hospitals. Can J Hosp Pharm. Mar 30, 2014;67(2):138-148. [FREE Full text] [CrossRef] [Medline]54] showed that integration with existing digital infrastructure is key to supporting a seamless workflow process to ensure all components of medication management (ie, prescribing, dispensing, and inventory control) are interconnected, enhancing efficiency and medication error prevention.

All the included studies focused on hospital-based automated medication-dispensing systems, with limited investigation in outpatient settings [Berdot S, Blanc C, Chevalier D, Bezie Y, Lê LMM, Sabatier B. Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet. Int J Qual Health Care. Apr 01, 2019;31(3):225-230. [FREE Full text] [CrossRef] [Medline]10,Risør BW, Lisby M, Sørensen J. Cost-effectiveness analysis of an automated medication system implemented in a Danish hospital setting. Value Health. Jul 2017;20(7):886-893. [FREE Full text] [CrossRef] [Medline]31,Risør BW, Lisby M, Sørensen J. Comparative cost-effectiveness analysis of three different automated medication systems implemented in a Danish hospital setting. Appl Health Econ Health Policy. Feb 8, 2018;16(1):91-106. [CrossRef] [Medline]32,Maviglia SM. Cost-benefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. Apr 23, 2007;167(8):788. [CrossRef]36]. Williams et al [Williams V, Haumba S, Ngwenya-Ngcamphalala F, Mafukidze A, Musarapasi N, Byarugaba H, et al. Implementation of the automated medication dispensing system-early lessons from Eswatini. Int J Public Health. Oct 12, 2023;68:1606185. [FREE Full text] [CrossRef] [Medline]52] demonstrated that automated medication-dispensing systems for chronic medication regimens, such as antiretroviral therapy, enable efficient one-time password (OTP)–based medication collection and reduced waiting times, benefiting high-volume, resource-limited outpatient clinics. Further studies may adopt this system for less complex medication regimens to improve patient satisfaction and reduce the staff burden, enabling health care providers to focus on other critical tasks, such as optimization of drug therapy [Tsao NW, Lo C, Babich M, Shah K, Bansback NJ. Decentralized automated dispensing devices: systematic review of clinical and economic impacts in hospitals. Can J Hosp Pharm. Mar 30, 2014;67(2):138-148. [FREE Full text] [CrossRef] [Medline]54,Gray J, Ludwig B, Temple J, Melby M, Rough S. Comparison of a hybrid medication distribution system to simulated decentralized distribution models. Am J Health Syst Pharm. Aug 01, 2013;70(15):1322-1335. [CrossRef] [Medline]55].

Targeting medication errors with a substantial clinical impact was a key strategy in the technology-based pharmacist-led outreach [Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. Apr 2012;379(9823):1310-1319. [CrossRef]15,Elliott RA, Putman KD, Franklin M, Annemans L, Verhaeghe N, Eden M, et al. Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER). Pharmacoeconomics. Jun 18, 2014;32(6):573-590. [CrossRef] [Medline]37]. As around 1% of medication errors lead to actual harm, prioritizing interventions is essential [Bates DW, Boyle DL, Vliet MBV, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. Apr 1995;10(4):199-205. [CrossRef]24]. The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) developed an index to standardize the classification of medication errors based on severity (ie, no error, error-no harm, error-harm, and error-death), which has been adopted in the hospital setting [About medication errors. National Coordinating Council for Medication Error Reporting and Prevention. Feb 2001. URL: https://www.nccmerp.org/about-medication-errors [accessed 2025-01-23] 56,Snyder RA, Abarca J, Meza JL, Rothschild JM, Rizos A, Bates DW. Reliability evaluation of the adapted National Coordinating Council Medication Error Reporting and Prevention (NCC MERP) index. Pharmacoepidemiol Drug Saf. Sep 24, 2007;16(9):1006-1013. [CrossRef] [Medline]57]. An initiative to standardize the interception of medication errors using this severity classification index has proven effective to prevent clinically significant patient harm and provide substantial cost savings to the health system [Cabri A, Barsegyan N, Postelnick M, Schulz L, Nguyen V, Szwak J, et al. Pharmacist intervention on prescribing errors: use of a standardized approach in the inpatient setting. Am J Health Syst Pharm. Nov 23, 2021;78(23):2151-2158. [FREE Full text] [CrossRef] [Medline]58].

Various economic models were used in the included studies (eg, quasi-experimental design, RCT, decision analytic model), indicating the complexity and multifaceted nature of DHT for medication safety. Sculpher et al [Sculpher MJ, Claxton K, Drummond M, McCabe C. Whither trial-based economic evaluation for health care decision making? Health Econ. Jul 20, 2006;15(7):677-687. [CrossRef] [Medline]59] emphasized the importance of placing an RCT within a broader framework of evidence synthesis and decision analysis in economic evaluation studies to balance internal validity and broader applicability. Quasi-experimental design can be practical for assessing real-world effectiveness and scalability. However, the assessment of confounders that might affect the observed trend and the lack of guidance in conducting economic evaluations alongside quasi-experimental trials necessitate careful interpretation of the findings [Deidda M, Geue C, Kreif N, Dundas R, McIntosh E. A framework for conducting economic evaluations alongside natural experiments. Soc Sci Med. Jan 2019;220:353-361. [FREE Full text] [CrossRef] [Medline]60].

Strengths and Limitations

This study is the first systematic review investigating economic evaluations of DHT interventions to improve medication safety outcomes. We conducted a rigorous literature search with a comprehensive strategy encompassing a wide range of DHT intervention types to provide a thorough review of different strategies to improve medication safety. We also included evaluations on methodological challenges in DHT intervention assessment to inform future research direction.

Nevertheless, our review has several potential limitations. First, the generalizability of findings may be restricted to high-income settings, as most included studies were conducted in such contexts. Second, heterogeneity in health care settings, study designs, and economic evaluation methods may hinder direct comparisons across studies. Despite this, a narrative synthesis was developed to integrate and interpret the findings. Third, the exclusion of non-English studies may have limited the comprehensiveness of the evidence base. Finally, there was a lack of medication error and ADE severity classification among the included studies. Since different medication errors and ADEs have varying cost implications, this variability makes the interpretation of overall cost-effectiveness less straightforward.

Conclusion

DHT interventions are economically viable to improve medication safety, with substantial reduction in ADEs and medication errors. On average, DHT interventions reduced ADEs by 37.12% and medication errors by 54.38%. In 92.3% of the included studies, DHT was either cost-effective or cost beneficial compared to standard care. Despite a significant upfront cost, DHT showed an ROI within 3-4.25 years. The key drivers of cost-effectiveness include reductions in outcomes, the proportion of errors resulting in ADEs, and implementation costs. Key methodological challenges included short follow-up periods, the absence of compliance tracking, the lack of ADE severity categorization, and the omission of indirect costs. Future studies should prioritize incorporating alert compliance tracking, ADE and medication error severity classification, and the evaluation of indirect costs, thereby increasing clinical benefits and economic viability.

Acknowledgments

This study was supported by an Academic Leadership Grant (ALG) from Padjadjaran University in 2024 through AAS.

Conflicts of Interest

None declared.

Multimedia Appendix 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist.

PDF File (Adobe PDF File), 66 KB

Multimedia Appendix 2

Clinical and economic outcomes of the included studies.

DOCX File , 27 KB

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ACE: angiotensin-converting enzyme
ADC: automated dispensing cabinet
ADE: adverse drug event
AMS: automated medication system
CBA: cost-benefit analysis
CBR: cost-benefit ratio
CDSS: clinical decision support system
CEA: cost-effectiveness analysis
CHEERS: Consolidated Health Economic Evaluation Reporting Standards
CMA: cost minimization analysis
CPOE: computerized provider order entry
CUA: cost-utility analysis
DDI: drug-drug interaction
DHT: digital health technology
GP: general practitioner
ICER: incremental cost-effectiveness ratio
MeSH: Medical Subject Headings
mHealth: mobile health
NSAID: nonsteroidal anti-inflammatory drug
PPI: proton pump inhibitor
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
QALY: quality-adjusted life year
RCT: randomized controlled trial
ROI: return on investment


Edited by A Schwartz; submitted 20.08.24; peer-reviewed by J Aarts, J Waterson; comments to author 25.09.24; revised version received 03.12.24; accepted 08.01.25; published 05.02.25.

Copyright

©Widya Norma Insani, Neily Zakiyah, Irma Melyani Puspitasari, Muhammad Yorga Permana, Kankan Parmikanti, Endang Rusyaman, Auliya Abdurrohim Suwantika. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.02.2025.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.