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. 2025 Sep 4;20(9):e0330946. doi: 10.1371/journal.pone.0330946

Cost-effectiveness of virtual emergency care models: A protocol for a systematic review

Ravi Shankar 1,*, Linda Wang 2, Ho Soon Hoe 2, Liew Mei Fong 2,3, Satya Pavan Kumar Gollamudi 4,5, Serene Wong 2,3,4
Editor: Vijay S Gc6
PMCID: PMC12410708  PMID: 40906671

Abstract

Background

The COVID-19 pandemic has accelerated the adoption of virtual care models in emergency medicine. While virtual emergency care has the potential to expand access, improve efficiency, and reduce costs, rigorous evaluation of its cost-effectiveness compared with traditional in-person emergency care is needed.

Objective

This systematic review aims to comprehensively search the literature, critically appraise the evidence, and synthesize findings on the cost-effectiveness of virtual emergency care models compared to in-person emergency care.

Methods

We will search PubMed, Web of Science, Embase, CINAHL, MEDLINE, The Cochrane Library, PsycINFO, and Scopus from 2010 to February 2025 for economic evaluations that report both costs and effects comparing virtual and in-person emergency care models. Studies that compare multiple virtual interventions without an in-person care comparator will be excluded. Two reviewers will independently screen studies, extract data, and assess methodological quality and risk of bias using established quality assessment tools. Covidence software will be used to manage the screening and data extraction process. A narrative synthesis and quantitative meta-analysis of incremental cost-effectiveness ratios (ICERs) will be conducted if appropriate.

Discussion

This review will provide a comprehensive evidence synthesis on the cost-effectiveness of virtual emergency care to guide clinical implementation, health policy, and future research. Findings will be highly relevant as virtual care becomes increasingly integrated into emergency care delivery in the aftermath of the COVID-19 pandemic.

PROSPERO registration

CRD42025648218

Introduction

Emergency departments (EDs) worldwide face persistent challenges of overcrowding, prolonged wait times, and escalating healthcare costs [13]. ED crowding is associated with treatment delays, medical errors, patient dissatisfaction, and increased morbidity and mortality [4,5]. Concurrently, the rising costs of emergency care strain patients, insurers, and health systems [6]. In 2017, US EDs accounted for 4.4% of total US health expenditures, or $76.3 billion [7,8].

Virtual emergency care, encompassing telemedicine, remote monitoring, and digital triage, has been increasingly proposed as a strategy to mitigate these challenges by expanding access, improving efficiency, and reducing costs [911]. Virtual ED consultations enable remote assessment and management of conditions that may not require in-person care, through synchronous (e.g., video) or asynchronous (e.g., text) digital interactions between patients and emergency providers [12,13]. Remote provider-to-provider teleconsultations, such as telestroke or teletrauma, connect ED providers with specialists to guide time-critical decisions [14]. Digital triage tools, such as web-based symptom checkers or chatbots, provide automated risk assessment, self-care guidance, or ED referral [15]. Remote physiological monitoring devices enable continuous tracking and alerts for specific high-risk conditions such as sepsis or acute heart failure [16,17].

The COVID-19 pandemic catalyzed a rapid uptake of virtual emergency care models around the world [18,19]. For example, in the US, ED telemedicine visits increased 16-fold between January and July 2020 compared with the same time period in 2019 [20]. The pandemic experience highlighted the potential for virtual modalities to facilitate triage, conserve protective equipment, reduce exposure risks, and preserve ED capacity [21]. Yet it also exposed barriers related to technology access, digital literacy, health equity, diagnostic uncertainty, and information security [22,23].

As the pandemic subsides, health systems and emergency care providers must decide whether and how to sustain virtual models as part of the standard practice [24]. A key consideration is cost-effectiveness – whether virtual emergency care provides sufficient value compared to traditional in-person care to justify ongoing investments. Some economic models suggest that virtual ED triage and consultations can reduce costs by diverting low-acuity visits, or by substituting for costlier in-person care [3,25,26]. However, there are also concerns that virtual visits may duplicate rather than replace in-person visits, increasing overall costs and utilization [27].

Prior systematic reviews on virtual emergency care have focused on clinical effectiveness or implementation outcomes [2830], with limited evaluations of economic impact. Existing economic reviews have focused on specific conditions like acute stroke [31], or specific technologies like wearables [32], with less attention to system-wide emergency care costs. To inform post-pandemic emergency care redesign, a comprehensive synthesis of economic evidence on virtual emergency care is urgently needed.

A preliminary scoping search conducted in PubMed identified approximately 150 potentially relevant studies, suggesting sufficient literature exists to warrant this comprehensive systematic review. The scoping search revealed heterogeneity in virtual care modalities, outcome measures, and economic evaluation methods, supporting our planned narrative synthesis approach.

Objective

This systematic review aims to evaluate the cost-effectiveness of virtual emergency care models compared to traditional in-person emergency care. While our primary focus is on economic outcomes, we will extract and report implementation barriers and facilitators as secondary findings when reported in included economic evaluations.

Methods

This systematic review will be conducted and reported according to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines [33] and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) [34].

Eligibility criteria

We will select studies according to the following PICOS (Population, Intervention, Comparator, Outcomes, Study design) criteria.

Population.

Patients of any age with emergency conditions that are the focus of a virtual care intervention. Emergency conditions are defined as acute illnesses or injuries that require immediate medical attention to prevent death or disability, as assessed by triage personnel, emergency providers, or patients themselves. Both undifferentiated emergency presentations (e.g., chest pain) and specific diagnoses (e.g., acute stroke) will be included. We will exclude studies on non-emergent conditions, elective procedures, or hospital inpatients without preceding ED care.

Intervention.

Any acute care delivery model that uses virtual modalities to manage emergency conditions as an alternative or adjunct to in-person emergency care. Virtual modalities include:

  • Synchronous or asynchronous telemedicine consultations between patient and emergency provider

  • Remote provider-to-provider telemedicine consults between ED and specialists

  • Web or mobile-based triage tools for symptom assessment, self-care guidance or disposition

  • Wearable devices or remote monitoring systems for high-risk emergency conditions

Hybrid models that combine initial virtual assessment with selective in-person care (e.g., mobile stroke units) will be included.

Comparator.

Usual in-person emergency care, delivered through face-to-face patient-provider interactions in a hospital-based emergency department. This may involve an initial in-person triage assessment by a nurse, and subsequent in-person evaluation and management by an emergency physician or advanced practice provider.

Outcomes.

The primary outcome is the incremental cost-effectiveness ratio (ICER), calculated as the difference in mean costs between virtual and in-person models divided by the difference in mean effectiveness. Costs should be reported from the health system or societal perspective, inflated to a common currency and year. Effectiveness should be measured using validated clinical (e.g., mortality), patient-centered (e.g., quality of life), or process (e.g., ED throughput) outcomes. Secondary outcomes include incremental costs and effects (even when not reported as ICERs), net monetary benefit, and sensitivity analyses.

Study designs.

We will include full economic evaluations that compare both costs and effects of virtual and in-person emergency care models. Eligible designs include cost-effectiveness analysis (using clinical or process outcomes), cost-utility analysis (using quality-adjusted life years or QALYs), cost-benefit analysis (monetizing health outcomes), and cost-minimization analysis (assuming equal effectiveness). Both model-based and trial-based evaluations will be included.

Exclusion criteria.

We will exclude studies that:

  • Do not involve an emergency condition or emergency care setting

  • Compare multiple virtual interventions without an in-person care comparator

  • Do not report both costs and effectiveness outcomes

  • Are not original research (e.g., reviews, editorials, commentaries)

  • Are published before 2010, as virtual care technologies have advanced significantly in the last decade

Geographic and language scope.

Studies from all countries will be included to capture the global evidence base on virtual emergency care cost-effectiveness. No language restrictions will be applied, ensuring that relevant studies published in any language are considered for inclusion. Efforts will be made to translate non-English studies where necessary to facilitate comprehensive analysis.

Information sources and search strategy

We will conduct a comprehensive search across multiple electronic bibliographic databases from 2010 to February 2025. The databases included in our search strategy are PubMed, Web of Science, Embase, CINAHL, MEDLINE, The Cochrane Library, PsycINFO, and Scopus. This extensive approach ensures a thorough and systematic review of the relevant literature, capturing a wide range of studies across various disciplines.

A search strategy will be developed for each database using a combination of keywords and controlled vocabulary terms (e.g., MeSH) related to (1) emergency care, (2) virtual care models, and (3) economic evaluations. An example of a search string is:

((virtual OR telehealth OR telemedicine OR digital OR “remote consult*” OR mHealth OR eHealth OR “mobile health” OR “web-based” OR wearable* OR “remote monitoring”) AND (emergency OR emergencies OR ED OR ER OR “emergency department”) AND (“cost effectiv*” OR “cost utility” OR “cost benefit” OR “cost minimization” OR “economic evaluation”))

Additional search filters will be applied for publication date (2010-present). We will also hand-search reference lists of included studies and relevant reviews for additional eligible studies. Grey literature sources such as clinical trial registries, conference proceedings, and preprint servers will be searched to identify unpublished studies. The full search strategy for each database will be developed in consultation with a medical librarian.

Study selection

Two reviewers will independently screen titles and abstracts of search results against the pre-specified PICOS criteria using Covidence systematic review software [35]. Records will be classified as “yes”, “no” or “maybe” for inclusion. The full text of potentially eligible studies classified as “yes” or “maybe” by either reviewer will be retrieved for further assessment.

The two reviewers will then independently review the full text of these studies using a standardized screening form with the detailed PICOS criteria. Reasons for exclusion will be recorded. Disagreements will be resolved through discussion or arbitration by a third reviewer.

The study selection process will be documented in a PRISMA flow diagram indicating the number of studies identified, included and excluded, with reasons for exclusion. The full list of studies excluded after full-text review will also be provided.

Data extraction

A standardized data extraction form will be developed based on the CHEERS reporting standards and piloted on a sample of five included studies. Two reviewers will independently extract data from all included studies using Covidence, with any discrepancies resolved through consensus or by involving a third reviewer. The extracted data will cover several key areas, including bibliographic details, participant characteristics, interventions, comparators, outcomes, and study-specific details.

Bibliographic details will include the first author, publication year, journal, and funding sources. Participant characteristics will capture inclusion and exclusion criteria, sample size, age (mean, standard deviation, range), sex distribution (% female), emergency conditions, triage acuity levels, and comorbidities. Intervention data will focus on the virtual care model used (e.g., ED-based telemedicine, teletriage, remote monitoring), the technological medium (e.g., video, telephone, web, mobile app), provider type (e.g., physician, nurse, advanced practice provider), frequency and duration of the intervention, and its relationship to in-person care (e.g., standalone, triage, step-up/step-down models).

Comparator details will include a description of usual in-person emergency care, specifying the providers, processes, and resources involved. Outcomes will be assessed through measures such as the incremental cost-effectiveness ratio (ICER) and its components, the type and source of effectiveness data (e.g., QALYs from trials, ED length of stay from administrative data), and the type and source of cost data (e.g., payer, hospital, patient costs). Other economic evaluation factors will be documented, including the analysis perspective (e.g., healthcare system, societal), time horizon, discount rate, sensitivity analyses (e.g., probabilistic, deterministic), and subgroup analyses.

Study details will cover the country and setting, analytic approach (e.g., within-trial, model-based), model structure and assumptions, utility scores and sources, cost sources and currency, and the approach to handling missing data (Details in Appendix 1 S1 File).

Risk of bias assessment

The methodological quality and risk of bias of included economic evaluations will be independently assessed by two reviewers using the Drummond 10-item quality assessment tool and the Consensus Health Economic Criteria (CHEC) 19-item quality assessment tool [3638]. The Drummond tool evaluates key aspects such as clarity of research questions, description of alternatives, effectiveness evidence, cost and consequence identification, valuation, adjustment for time differences, incremental analysis, uncertainty consideration, and user relevance. The CHEC tool assesses study population clarity, research question formulation, appropriateness of study design and time horizon, perspective selection, cost and outcome identification, measurement and valuation, incremental analysis, discounting, sensitivity analysis, result generalizability, conflict of interest disclosure, and ethical considerations (Details in S1 File).

The quality assessment results will be reported in tables with color coding for risk of bias: green (low), yellow (some concerns), or red (high). Results will also be summarized narratively and inform the overall quality of the evidence (e.g., using GRADE economic criteria) [39].

Synthesis and analysis

A narrative synthesis, following the Synthesis Without Meta-analysis (SWiM) guidelines [40], will first summarize key characteristics and findings of included economic evaluations in text and tabular form. Tables will report details on populations, interventions, comparators, analytic approach, cost and outcome measures, and ICERs. We will compare cost-effectiveness results across studies and explore potential reasons for variability, such as differences in health systems, methodological choices, or evaluative scope.

In cases of significant methodological heterogeneity across included studies, we will employ a structured approach to narrative synthesis. Studies will be categorized by virtual care modality (e.g., synchronous video, asynchronous messaging, remote monitoring), clinical context (e.g., undifferentiated ED presentations, specific conditions like stroke), and economic evaluation type. Within each category, we will identify patterns in cost-effectiveness findings and contextualize results based on healthcare setting, patient population, and implementation factors. When outcome measures differ substantially, we will standardize results to common metrics where possible (e.g., converting to cost per quality-adjusted life year) or focus on reporting relative rather than absolute economic outcomes [41,42].

If there are two or more studies with sufficiently homogeneous populations, interventions and methods, we will pool ICERs using fixed or random-effects meta-analysis [43]. Heterogeneity will be assessed statistically (e.g., I2) and through subgroup analyses based on key study-level characteristics (e.g., virtual care model, patient acuity, country). Sensitivity analyses will examine the impact of study quality. Publication bias will be assessed visually through funnel plots and statistically using Egger’s test [44].

If meta-analysis is not appropriate, we will focus on describing economic findings narratively and identifying key drivers of cost-effectiveness across studies. We will also summarize implementation issues, evidence gaps, and methodological challenges to guide future economic evaluation efforts in virtual emergency care.

All analyses will be conducted in R version 4.0.

Confidence in cumulative evidence

We will apply the GRADE approach to rate the certainty of economic evidence for each outcome as high, moderate, low, or very low [45]. Ratings will be based on risk of bias, imprecision, inconsistency, indirectness, and publication bias assessments. The implications of these ratings for decision-making will be discussed.

GRADE ratings will directly inform how findings can guide health policy decisions. For outcomes with high-certainty evidence, we will provide specific implementation recommendations. For moderate-certainty evidence, we will suggest consideration with appropriate monitoring mechanisms. For low or very-low certainty evidence, we will emphasize the need for caution and additional research before widespread implementation. GRADE criteria will be applied to all included studies regardless of methodological quality threshold, with sensitivity analyses conducted to assess the impact of excluding lower-quality studies on overall conclusions.

Stakeholder engagement

Representatives from key stakeholder groups (emergency physicians, health economists, hospital administrators, payers, and patient advocates) will be engaged early in the review process to inform data extraction priorities, outcome interpretation, and knowledge translation planning. This engagement will occur through structured consultations during protocol refinement and preliminary findings review.

Living systematic review approach

This systematic review will be maintained as a living review, with planned updates conducted annually or when substantial new evidence becomes available. Updated searches will use the same methodology, with screening and data extraction conducted by the same research team to ensure consistency. Stakeholders will be notified of significant updates through our knowledge translation networks [46].

Discussion

This protocol outlines a systematic and comprehensive approach to evaluating the cost-effectiveness of virtual emergency care models compared to traditional in-person care. The COVID-19 pandemic has accelerated the adoption of virtual care in emergency medicine, but the economic value of these models remains uncertain. This systematic review aims to address this evidence gap by synthesizing the highest quality economic evaluations available to inform clinical implementation, health policy, and future research directions.

The protocol ensures methodological rigor which is a key strength of the systematic review. By adhering to best practice guidelines for systematic review (PRISMA), health economic evaluations (CHEERS), and synthesis without meta-analysis (SWiM), the protocol ensures transparency, reproducibility, and sound methodology. The inclusion and exclusion criteria are clearly specified using the PICOS framework, covering a broad range of virtual care modalities, emergency conditions, and economic outcomes. The search strategy is comprehensive, leveraging both academic databases and grey literature sources, and will be iteratively developed in consultation with a medical librarian to optimize sensitivity and specificity.

The planned use of independent dual review and standardized data extraction forms adapted from the CHEERS reporting standards aim to minimize the risk of bias and errors in study selection and data collection. Assessment of methodological quality and risk of bias using the Drummond and CHEC checklists will provide a transparent evaluation of the internal and external validity of included studies. Results will inform the certainty of evidence ratings using the GRADE approach. If appropriate, quantitative synthesis using meta-analysis will pool ICERs to provide summary estimates of cost-effectiveness, with exploration of heterogeneity through subgroup and sensitivity analyses, as demonstrated by Noparatayaporn et al. [47], which evaluated the cost-effectiveness of bariatric surgery across different patient subgroups and time horizons through a meta-analysis of incremental net monetary benefit. If quantitative synthesis is not possible, narrative synthesis following SWiM guidelines will summarize key findings, explore heterogeneity across studies, and identify implications for policy and research.

Anticipated limitations of the review largely reflect the current state of evidence in this rapidly evolving field. The COVID-19 pandemic catalyzed numerous virtual emergency care initiatives and research studies, but many are likely still ongoing or unpublished. The lag in dissemination of findings may result in a skewed evidence base that over-represents earlier, less mature virtual care models and fails to capture longer-term economic outcomes. The inclusion of pre-prints and grey literature aims to mitigate publication bias, but the planned assessment of publication bias will be important to contextualize the findings.

Another challenge relates to the significant heterogeneity expected across studies in terms of populations, interventions, comparators, methods, and contexts. Variability in virtual care modality, technological platform, staffing models, clinical protocols, and payment structures may preclude fair comparisons of cost-effectiveness across studies. Inconsistency in costing methods, cost and outcome measures, time horizons, and analytic perspectives may further limit quantitative pooling of ICERs. However, the use of established economic evaluation reporting standards (CHEERS) and quality assessment tools (Drummond, CHEC) to critically appraise studies and a narrative synthesis approach (SWiM) to explore heterogeneity can still yield valuable insights to guide decision-making.

Next steps following this protocol involve executing the systematic review according to the pre-specified methods. This will require close collaboration among a multidisciplinary team of emergency clinicians, health economists, systematic review methodologists, and informatics experts. Adaptations to the protocol may be necessary based on the volume and characteristics of the evidence base, with any deviations transparently reported.

Findings will be rapidly disseminated through academic publications, conference presentations, and briefs targeted to key emergency care stakeholders, including healthcare providers, payers, policymakers, patient advocates, and technology vendors. Plain-language summaries, infographics, and evidence maps can enhance the accessibility and impact of results for diverse audiences. Insights will be contextualized to different health systems and policy environments to facilitate local adaptation and implementation.

To maximize real-world application beyond academic audiences, findings will be translated into targeted knowledge products for key stakeholders: (1) policy briefs for health ministries and regulatory bodies highlighting cost-effectiveness thresholds and policy implications; (2) implementation toolkits for hospital administrators with economic modeling templates and budget impact analyses; (3) strategic reports for telehealth providers identifying sustainable reimbursement models; (4) value-based payment frameworks for insurance companies and payers; and (5) decision aids for patients and consumer advocates explaining economic trade-offs and access considerations. We will engage representatives from each stakeholder group to ensure these knowledge translation products address practical decision-making needs.

In parallel, a key research priority will be to update this systematic review on an ongoing basis as new economic evaluations of virtual emergency care models are published. Living systematic reviews can help keep pace with the rapidly evolving evidence base and inform real-time decision-making. Establishing a shared repository for standardized reporting of economic outcomes for virtual emergency care can further facilitate evidence synthesis and cross-study comparisons.

Ultimately, this systematic review aims to provide actionable economic evidence to guide the implementation of virtual emergency care models that enhance patient access, improve population health outcomes, and lower costs. By identifying cost-effective models and implementation best practices, the review can accelerate evidence-based integration of virtual care into routine emergency care delivery. At a health system level, this can support progress towards the quadruple aim of better care experiences, better population health, lower costs, and improved provider well-being [48,49]. Demonstrating the economic value of virtual emergency care can also help secure sustainable funding, incentives, and infrastructure to support ongoing telehealth innovation and evaluation in emergency medicine.

This systematic review protocol represents a rigorous and comprehensive approach to synthesizing economic evidence on virtual emergency care, a rapidly evolving area with significant policy and practice implications in the post-pandemic era. Adherence to best practice guidelines for systematic reviews and health economic evaluations strengthens the methodological quality, transparency, and reproducibility of the planned review. The results will equip health system leaders, payers, and policymakers with critical economic insights to guide evidence-based integration of cost-effective virtual emergency care models. Findings will also highlight priority areas for future economic evaluations to strengthen the evidence base on virtual emergency care. As both an emergency physician and health services researcher dedicated to telehealth innovation, I believe this systematic review is a crucial step towards realizing the potential of virtual care in emergency medicine to enhance the quadruple aim and advance health system value.

Supporting information

S1 Checklist. PRISMA-P Checklist.

(DOC)

pone.0330946.s001.doc (84KB, doc)
S1 File. Supplementary file.

(DOCX)

pone.0330946.s002.docx (20.2KB, docx)

Data Availability

No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Vijay S Gc

1 Aug 2025

Please submit your revised manuscript by Sep 15 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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PLOS ONE

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2. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

- Please move the planned use of the PICOS framework, the use of the PRISMA guidelines and the CHEERS checklist to the appropriate place in the Methods section. 

- CHEERS is a reporting checklist for health economic evaluations, the Drummond checklist is to assess the quality of economic evaluation, and the CHEC checklist is a tool to assess the methodological quality of economic evaluation. These are used interchangeably in the manuscript as a checklist, quality assessment tool and guideline for economic evaluation. Please correct this throughout the manuscript and make appropriate adjustments.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: Thank you for the chance to review this article. I found it to be well written, clear in its description, timely and of interest. I have cross checked with PRISMA guidelines and it is well described. Below are some specific comments and suggestions, none of which are major.

Data policy/sharing

I think it is necessary to include the statement "No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion." within the manuscript text. I suggest at the end of methods, or elsewhere as suggested by the editors. If included in methods, it could be combined with further details on how a living systematic review will be maintained.

Issues that must be addressed:

Ln 28 & 54: "from inception to February 2025" - elsewhere it states that publications prior to 2010 will be exluded. Amend or explain further why including the in the search.

Ln 46: Statistic is unclear. Is it 4.4% of total US health expenditure?

Ln 61: This statistic is unclear. should it say "increased 16-fold between January and July 2020 compared with the same time period in 2019"?

Ln 131-132: In outcomes, make it clear that you will include reported costs and effects even if these are not reported with an ICER.

Inclusions/Exclusions: make it clearer what countries will be included in the review and what languages (all?)

Ln 247: add reference at end of this line for methods described.

Ln 248: I believe "2" of "I2" should be super-script.

Ln 251: Add reference at the end of the line.

Ln 353-354: making this a living systematic review is commendable. I think some further description should be added to the methods. Also, please include reference (Cochrane 2019).

Ln 363: Include reference for "quadruple aim". Berwick 2018 & Sikka BMJ 2015?

Optional suggestions:

Ln24-26: Replace with objective given in main text as I found this clearer.

Ln 29: suggest after "evaluation" add "that report both costs and effects"

Ln 29: Add exclusions: "Studies that compare multiple virtual interventions without an in person care comparator will be excluded" as advised by PRISMA

Ln 64-65: Will these barriers be explored in the review? If so, this could be made clearer in methods/discussion.

General: has a scoping search been done and, if so, what were the findings?

Ln 84-103: I find this "Frameworks" section a helpful summary. Perhaps add CHEC/Drummond, SWiM and GRADE.

Ln 125-126: Delete final sentence as this is covered in "exclusions".

Ln 143-144: Delete final sentence as this is covered in "exclusions".

Ln 243-245: Can you provide a reference for this? Example of where it's been done before?

Ln 279: replace "and" with ", which".

Ln 286: replace "was" with "will be".

Ln 290-293: Long and confusing sentence. Suggest full stop after "studies" on ln 292, then rewording remaining part of sentence.

Ln 295: if possible, add reference by way of an example of pooled ICERs.

Ln 299-311: Whole paragraph is repetitive of introduction and I think could be removed here.

Ln 339: add "s" at end of "system"

Ln 348-350: I would consider involving representitives at an earlier stage in your reserach (as early as possible) and describing their inolvement, how this can inform the research, in the methods.

Best of luck with the review and I look forward to reading the results in the future.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes:  Sarah Pyne

**********

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PLoS One. 2025 Sep 4;20(9):e0330946. doi: 10.1371/journal.pone.0330946.r002

Author response to Decision Letter 1


2 Aug 2025

Response to Reviewer Comments and Manuscript Changes

We thank both the Editor and reviewer for their thoughtful and constructive feedback on our manuscript. We have carefully addressed each point and made appropriate revisions to strengthen the protocol. Below we provide detailed responses to each comment. We have also attached a MS word file with Response to Reviewer Comments and Manuscript Changes in tabular form.

Response to Editor Comments

S.No. 1 - Editor Comment: Please move the planned use of the PICOS framework, the use of the PRISMA guidelines and the CHEERS checklist to the appropriate place in the Methods section.

Response: We thank the editor for this important structural suggestion. We have moved the description of PICOS, PRISMA, and CHEERS from the separate "Frameworks" section to their appropriate locations within the Methods section for better organization and flow.

Changes Made in Manuscript:

Deleted: Entire "Frameworks" section (lines 83-102 in original manuscript)

Added: After "Methods" heading (line 92): "This systematic review will be conducted and reported according to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines [33]" (lines 93-94)

Added: After "Eligibility criteria" heading (line 95): "We will select studies according to the following PICOS (Population, Intervention, Comparator, Outcomes, Study design) criteria:" (lines 96-97)

Added: Additional text about preliminary scoping search and implementation barriers (lines 81-90)

S.No. 2 - Editor Comment: CHEERS is a reporting checklist for health economic evaluations, the Drummond checklist is to assess the quality of economic evaluation, and the CHEC checklist is a tool to assess the methodological quality of economic evaluation. These are used interchangeably in the manuscript as a checklist, quality assessment tool and guideline for economic evaluation. Please correct this throughout the manuscript and make appropriate adjustments.

Response: We acknowledge this important clarification and have corrected the terminology throughout the manuscript. CHEERS is now consistently referred to as "reporting standards" for data extraction, while Drummond and CHEC are referred to as "quality assessment tools" for evaluating methodological quality and risk of bias.

Changes Made in Manuscript:

Line 32: Changed "assess methodological quality and risk of bias using the Drummond and CHEC checklists" to "assess methodological quality and risk of bias using established quality assessment tools"

Line 181: Changed "A standardized data extraction form will be developed based on the CHEERS checklist" to "A standardized data extraction form will be developed based on the CHEERS reporting standards"

Lines 209-211: Changed "using the Drummond 10-item checklist and the Consensus Health Economic Criteria (CHEC) 19-item checklist" to "using the Drummond 10-item quality assessment tool and the Consensus Health Economic Criteria (CHEC) 19-item quality assessment tool"

Line 214: Changed "The CHEC checklist assesses" to "The CHEC tool assesses"

Line 296: Changed "adapted from the CHEERS checklist" to "adapted from the CHEERS reporting standards"

Lines 324-325: Changed "established economic evaluation guidelines (CHEERS, Drummond, CHEC)" to "established economic evaluation reporting standards (CHEERS) and quality assessment tools (Drummond, CHEC)"

Added: New sections on "Stakeholder engagement" (lines 265-270) and "Living systematic review approach" (lines 271-276)

Response to Comments from Reviewer 1

S.No. 1 - Reviewer Comment: Data policy/sharing: I think it is necessary to include the statement "No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion." within the manuscript text. I suggest at the end of methods, or elsewhere as suggested by the editors. If included in methods, it could be combined with further details on how a living systematic review will be maintained.

Response: We agree and have added a comprehensive data availability statement that also addresses the living systematic review approach.

Changes Made in Manuscript: Added separate sections for "Stakeholder engagement" (lines 265-270), "Living systematic review approach" (lines 271-276), and formal "Data availability" statement (lines 401-403).

S.No. 2 - Reviewer Comment: Ln 28 & 54: "from inception to February 2025" - elsewhere it states that publications prior to 2010 will be exluded. Amend or explain further why including the in the search.

Response: We acknowledge this inconsistency. We have corrected the search timeframe to align with our exclusion criteria.

Changes Made in Manuscript:

Line 28: Changed "from inception to February 2025" to "from 2010 to February 2025"

Line 149: Changed "from their inception to February 2025" to "from 2010 to February 2025"

S.No. 3 - Reviewer Comment: Ln 46: Statistic is unclear. Is it 4.4% of total US health expenditure?

Response: Yes, this refers to total US health expenditure. We have clarified this for precision.

Changes Made in Manuscript: Line 47: Changed "In 2017, US EDs accounted for 4.4% of total health expenditures" to "In 2017, US EDs accounted for 4.4% of total US health expenditures"

S.No. 4 - Reviewer Comment: Ln 61: This statistic is unclear. should it say "increased 16-fold between January and July 2020 compared with the same time period in 2019"?

Response: Correct, we have clarified the time period comparison for better precision.

Changes Made in Manuscript: Line 62: Changed "ED telemedicine visits increased 16-fold from January to July 2020 compared to 2019" to "ED telemedicine visits increased 16-fold between January and July 2020 compared with the same time period in 2019"

S.No. 5 - Reviewer Comment: Ln 131-132: In outcomes, make it clear that you will include reported costs and effects even if these are not reported with an ICER.

Response: We agree this clarification is important and have modified the outcomes section accordingly.

Changes Made in Manuscript: Lines 126-128: Changed "Secondary outcomes include incremental costs and effects, net monetary benefit, and sensitivity analyses" to "Secondary outcomes include incremental costs and effects (even when not reported as ICERs), net monetary benefit, and sensitivity analyses"

S.No. 6 - Reviewer Comment: Inclusions/Exclusions: make it clearer what countries will be included in the review and what languages (all?)

Response: We have added explicit geographic and language scope information to address this important methodological detail.

Changes Made in Manuscript: Added after line 141: "Geographic and language scope: Studies from all countries will be included to capture the global evidence base on virtual emergency care cost-effectiveness. No language restrictions will be applied, ensuring that relevant studies published in any language are considered for inclusion. Efforts will be made to translate non-English studies where necessary to facilitate comprehensive analysis." (lines 142-146)

S.No. 7 - Reviewer Comment: Ln 247: add reference at end of this line for methods described.

Response: We have added an appropriate reference for meta-analysis methods.

Changes Made in Manuscript: Line 242: Added reference [43] after "meta-analysis" and added "Borenstein, M., et al., Introduction to meta-analysis. 2021: John wiley & sons." to references (reference 43)

S.No. 8 - Reviewer Comment: Ln 248: I believe "2" of "I2" should be super-script.

Response: Correct, we have fixed the formatting.

Changes Made in Manuscript: Line 243: Changed "I2" to "I²"

S.No. 9 - Reviewer Comment: Ln 251: Add reference at the end of the line.

Response: We have added the appropriate reference for Egger's test.

Changes Made in Manuscript: Line 246: Added reference [44] and added "Egger, M., et al., Bias in meta-analysis detected by a simple, graphical test. Bmj, 1997. 315(7109): p. 629-34." to references (reference 44)

S.No. 10 - Reviewer Comment: Ln 353-354: making this a living systematic review is commendable. I think some further description should be added to the methods. Also, please include reference (Cochrane 2019).

Response: We appreciate this feedback and have expanded the living systematic review methodology in the methods section.

Changes Made in Manuscript: Added section "Living systematic review approach" (lines 271-276): "This systematic review will be maintained as a living review, with planned updates conducted annually or when substantial new evidence becomes available. Updated searches will use the same methodology, with screening and data extraction conducted by the same research team to ensure consistency. Stakeholders will be notified of significant updates through our knowledge translation networks [46]." Added Elliott reference (reference 46).

S.No. 11 - Reviewer Comment: Ln 363: Include reference for "quadruple aim". Berwick 2018 & Sikka BMJ 2015?

Response: We have added the appropriate references for the quadruple aim concept.

Changes Made in Manuscript: Line 361: Added references [48, 49] and added both Berwick and Sikka references to reference list (references 48 and 49)

S.No. 12 - Reviewer Comment: Ln24-26: Replace with objective given in main text as I found this clearer.

Response: We agree the main text objective is clearer and have updated the abstract accordingly.

Changes Made in Manuscript: Lines 24-26: Changed to "This systematic review aims to evaluate the cost-effectiveness of virtual emergency care models compared to in-person emergency care."

S.No. 13 - Reviewer Comment: Ln 29: suggest after "evaluation" add "that report both costs and effects"

Response: This clarification improves precision about our inclusion criteria.

Changes Made in Manuscript: Line 29: Changed to "for economic evaluations that report both costs and effects comparing virtual and in-person emergency care models"

S.No. 14 - Reviewer Comment: Ln 29: Add exclusions: "Studies that compare multiple virtual interventions without an in person care comparator will be excluded" as advised by PRISMA

Response: We have added this exclusion criterion to the abstract as suggested.

Changes Made in Manuscript: Added lines 30-31: "Studies that compare multiple virtual interventions without an in-person care comparator will be excluded."

S.No. 15 - Reviewer Comment: Ln 64-65: Will these barriers be explored in the review? If so, this could be made clearer in methods/discussion.

Response: While not our primary focus, we will extract barrier information when available. We have clarified this.

Changes Made in Manuscript: Added after line 66: "While our primary focus is on economic outcomes, we will extract and report implementation barriers and facilitators as secondary findings when reported in included economic evaluations." Also clarified in objective section (lines 87-90).

S.No. 16 - Reviewer Comment: General: has a scoping search been done and, if so, what were the findings?

Response: We conducted a preliminary scoping search and have added this information.

Changes Made in Manuscript: Added after line 80: "A preliminary scoping search conducted in PubMed identified approximately 150 potentially relevant studies, suggesting sufficient literature exists to warrant this comprehensive systematic review. The scoping search revealed heterogeneity in virtual care modalities, outcome measures, and economic evaluation methods, supporting our planned narrative synthesis approach." (lines 81-85)

S.No. 17 - Reviewer Comment: Ln 84-103: I find this "Frameworks" section a helpful summary. Perhaps add CHEC/Drummond, SWiM and GRADE.

Response: We agree this would make the frameworks section more comprehensive.

Changes Made in Manuscript: The frameworks mentioned are now integrated throughout the methods section where they are specifically applied: CHEC/Drummond in Risk of bias assessment section (lines 207-218), SWiM in Synthesis section (lines 224-225), GRADE in Confidence in cumulative evidence section (lines 253-256)

S.No. 18 - Reviewer Comment: Ln 125-126: Delete final sentence as this is covered in "exclusions".

Response: We agree this is redundant and have removed it.

Changes Made in Manuscript: Deleted redundant sentence from intervention section: "We will exclude studies comparing multiple virtual modalities without an in-person ED care arm."

S.No. 19 - Reviewer Comment: Ln 143-144: Delete final sentence as this is covered in "exclusions".

Response: We agree this is redundant and have removed it.

Changes Made in Manuscript: Deleted redundant sentence about partial economic evaluations from trial-based evaluations section (originally in lines 143-144)

S.No. 20 - Reviewer Comment: Ln 243-245: Can you provide a reference for this? Example of where it's been done before?

Response: We have added appropriate references for outcome standardization methods.

Changes Made in Manuscript: Added after line 240: "following established methods for standardizing economic outcomes across studies [41, 42]" and added corresponding references (Petrillo and Drummond references)

S.No. 21 - Reviewer Comment: Ln 279: replace "and" with ", which".

Response: Corrected for better grammar flow.

Changes Made in Manuscript: Line 286: Changed "and is a key strength" to "which is a key strength"

S.No. 22 - Reviewer Comment: Ln 286: replace "was" with "will be".

Response: Corrected verb tense for consistency.

Changes Made in Manuscript: Line 293: Changed "was iteratively developed" to "will be iteratively developed"

S.No. 23 - Reviewer Comment: Ln 290-293: Long and confusing sentence. Suggest full stop after "studies" on ln 292, then rewording remaining part of sentence.

Response: We have restructured this for better clarity.

Changes Made in Manuscript: Lines 297-300: Split into two sentences: "Assessment of methodological quality and risk of bias using the Drummond and CHEC checklists will provide a transparent evaluation of the internal and external validity of included studies. Results will inform the certainty of evidence ratings using the GRADE approach."

S.No. 24 - Reviewer Comment: Ln 295: if possible, add reference by way of an example of pooled ICERs.

Response: We have added example references of ICER pooling in economic evaluations.

Changes Made in Manuscript: Added after line 302: "as demonstrated in previous systematic reviews such as Noparatayaporn et al. [47], which evaluated the cost-effectiveness of bariatric surgery across different patient subgroups and time horizons through a meta-analysis of incremental net monetary benefit."

S.No. 25 - Reviewer Comment: Ln 299-311: Whole paragraph is repetitive of introduction and I think could be removed here.

Response: We agree this paragraph is redundant and have removed it.

Changes Made in Manuscript: Removed the repetitive paragraph about the protocol being timely and relevant (the content was streamlined and integrated elsewhere in the discussion)

S.No. 26 - Reviewer Comment: Ln 339: add "s" at end of "system"

Response: Corrected for proper grammar.

Changes Made in Manuscript: Line 337: Changed "health system" to "health systems"

S.No. 27 - Reviewer Comment: Ln 348-350: I would consider involving representitives at an earlier stage in your reserach (as early as possible) and describing their inolvement, how this can inform the research, in the methods.

Response: Excellent suggestion. We have added early stakeholder engagement to the methods section.

Changes Made in Manuscript: Added "Stakeholder engagement" section (lines 265-270): "Representatives from key stakeholder groups (emergency physicians, health economists, hospital administrators, payers, and patient advocates) will be engaged early in the review process to inform data extraction priorities, outcome interpretation, and knowledge translation planning. This engagement will occur through structured consultations during protocol refinement and preliminary findings review."

We believe these revisions have substantially strengthened the protocol while maintaining its core methodological rigor. The added details will enhance reproducibility and implementation. We welcome any additional feedback from the reviewers.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0330946.s004.docx (22.5KB, docx)

Decision Letter 1

Vijay S Gc

6 Aug 2025

Dear Dr. Shankar,

Thank you for submitting your revised manuscript to PLOS ONE. Following review of your manuscript, we invite you to submit a minor revision.

Please submit your revised manuscript by Sep 20 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Vijay S. Gc, PhD

Academic Editor

PLOS ONE

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

- Please recheck the references cited in the manuscript. Update the reference cited for Dilokthornsakul et al. [47] as the paper is not related to seasonal influenza vaccination. 

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PLoS One. 2025 Sep 4;20(9):e0330946. doi: 10.1371/journal.pone.0330946.r004

Author response to Decision Letter 2


6 Aug 2025

We thank the editor for the constructive feedback on our systematic review protocol manuscript "Cost-Effectiveness of Virtual Emergency Care Models: A protocol for a Systematic Review" (PONE-D-25-15708R1).

Regarding Journal Requirements on Citations: We acknowledge the guidance regarding reviewer-recommended citations and confirm that we have reviewed all references for their direct relevance to virtual emergency care cost-effectiveness and systematic review methodology. All 49 included references are appropriate and contribute meaningfully to the scientific foundation of our protocol.

Regarding Reference List Review: We have completed a comprehensive review of our entire reference list to ensure completeness and accuracy. All references have been verified as current publications that have not been retracted. Each reference is directly relevant to our study objectives, covering emergency medicine, telemedicine, health economics, and systematic review methodology. We confirmed that no problematic citations were included in our manuscript.

Regarding the Specific Reference Correction for Dilokthornsakul et al. [47]: We have corrected this important error. The reference [47] has been properly updated to reflect Noparatayaporn et al.'s work on the incremental net monetary benefit of bariatric surgery cost-effectiveness meta-analysis, which is the appropriate citation for the context in which it appears in our manuscript (lines 305-306 and 524-526). We have removed the previous incorrect reference to seasonal influenza vaccination research that was not relevant to our systematic review protocol. The corrected reference now accurately cites: "Noparatayaporn, P., et al., Incremental Net Monetary Benefit of Bariatric Surgery: Systematic Review and Meta-Analysis of Cost-Effectiveness Evidences. Obesity Surgery, 2021. 31(7): p. 3279-3290."

All requested revisions have been completed, and we have ensured that our reference list now accurately reflects the content and context of our systematic review protocol. The manuscript is ready for continued review consideration.

We believe these corrections strengthen the quality and accuracy of our submission.

Attachment

Submitted filename: Response_to_Reviewers_auresp_2.docx

pone.0330946.s005.docx (15.4KB, docx)

Decision Letter 2

Vijay S Gc

8 Aug 2025

Cost-Effectiveness of Virtual Emergency Care Models: A protocol for a Systematic Review

PONE-D-25-15708R2

Dear Dr. Shankar,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Vijay S. Gc, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Vijay S Gc

PONE-D-25-15708R2

PLOS ONE

Dear Dr. Shankar,

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Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. PRISMA-P Checklist.

    (DOC)

    pone.0330946.s001.doc (84KB, doc)
    S1 File. Supplementary file.

    (DOCX)

    pone.0330946.s002.docx (20.2KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    pone.0330946.s004.docx (22.5KB, docx)
    Attachment

    Submitted filename: Response_to_Reviewers_auresp_2.docx

    pone.0330946.s005.docx (15.4KB, docx)

    Data Availability Statement

    No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.


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