(19) The cost effectiveness of early assessment and intervention by a dedicated health and social care professional team for older adults in the emergency department compared to treatment-as-usual: Economic evaluation of the OPTI-MEND trial

SECTION: TITLE
The cost effectiveness of early assessment and intervention by a dedicated health and social care professional team for older adults in the emergency department compared to treatment-as-usual: Economic evaluation of the OPTI-MEND trial

SECTION: ABSTRACT
Background

Over 65s are frequent attenders to the Emergency Department (ED) and more than half are admitted for overnight stays. Early assessment and intervention by a dedicated ED-based Health and Social Care Professionals (HSCP) team reduces ED length of stay and the risk of hospital admissions among older adults while improving patient health-related quality-of-life and satisfaction with care. This study aims to evaluate whether augmenting the treatment as usual for older adults admitted to ED is cost-effective.

Methods and findings

Cost-effectiveness analysis (CEA), conducted alongside the OPTI-MEND randomised controlled trial of 353 patients aged =65 with lower urgency complaints compared the effectiveness of early assessment and intervention by a dedicated HSCP team in the ED to treatment as usual (TAU). An economic analysis estimated the average cost per older adults randomised to the HSCP team, and compared to TAU, how contact with HSCP team changed health care use, and associated total costs, and estimated the effect of HSCP on Quality-Adjusted Life Years (QALYs). Within the OPTI-MEND trial, the average cost of a contact with the HSCP team during ED attendance is estimated to be $801 per patient. Compared to TAU, the incremental QALY of intervention is 0.053 (95% CI: 0.023 to 0.0826, p0.0001). Accounting for cost savings because of contact with HSCP team, the average incremental saving in the total cost, compared to TAU, is -$6,128 (95% CI: -$9,217 to -$3,038, p0.0001). Given the incremental health gains and significant cost savings, bootstrapped cost CEA suggests that dedicated HSCP care dominates over TAU for low urgency older adults attending the ED.

Conclusions

A dedicated HSCP team in the ED significantly improves overall health for lower acuity older adults and, by reducing inpatient length of stay, results in staggering cost savings. This economic evaluation conducted on the OPTI-MEND trial provides convincing evidence that HSCP should be adopted as part of treatment as usual in Irish EDs.

Trial registration

ClinicalTrials.gov, NCT03739515; registered on 12th November 2018. https://classic.clinicaltrials.gov/ct2/show/NCT03739515.

SECTION: INTRO
Introduction

Older adults are frequent users of emergency departments (EDs) and, under treatment as usual (TAU), more than half of ED attendances result in inpatient admissions with a median length of stay of nine nights (interquartile range 5 to 24 nights). Hospital admissions are associated with increased ED wait times, shortages in hospital beds and complex admission pathways result in delayed length of stay (LoS) in the ED. The OPTI-MEND trial tested the effect of adding a dedicated team of Health and Social Care Professionals (HSCP) to the ED and concluded that early assessment and intervention for low urgency older people can facilitate shorter stays in the ED, reduced risk of hospital admissions and improve satisfaction with overall care.ith overall care. This health economic study extends on the clinical trial and, by using OPTI-MEND trial data, conducts a cost effectiveness analysis to inform policy on whether HSCPs may represent value for money.

Appraisal of the best available evidence suggests that interventions centred around care coordination in the ED may increase clinical effectiveness for older adults. Care Coordination Teams in the ED reduce rates of hospital admission, which motivated the hypothesis that, allocating a dedicated HSCP team who conducts early assessment and intervention, would result in better clinical and economic outcomes for lower acuity older adults. Specifically, HSCP teams are demonstrated to result in favourable discharge outcomes to home and enhanced continuity of care in the community which, on aggregate, should improve health-related quality-of-life and reduce demand for limited healthcare resources.

The OPTI-MEND trial was conducted to determine whether ED-based interdisciplinary HSCP teams are effective to reduce LoS in the ED and incidence of hospital admission among older adults. The HSCP team allocated into the ED included one additional senior physiotherapist, one senior occupational therapist, and one senior medical social worker to provide early assessment and intervention to lower acuity older adults. The team conducted interdisciplinary assessments of functional and mobility status, cognition, and psychosocial needs and subsequent interventions were tailored to individual older adults' needs (including, but not limited to, patient and family education on the outcome of the HSCP assessment and ED discharge plan, prescription of mobility aids and enabling Activities of Daily Living (ADL) equipment, provision of home exercise programmes, education of self-management strategies and onward referral to alternative care pathways). The primary clinical study found that, compared to usual ED care, HSCP teams were clinically effective in reducing ED length of stay (6.4 versus 12.1 median hours, p 0.001), and incidence of hospital admissions (19.3% versus 55.9%, p 0.001); this motivated the further hypothesis that dedicated HSCP teams for older adults should also be a cost effective service, and potentially cost saving, within the Irish health system.

To determine whether dedicated HSCP teams for older adults in the ED represent value to the Irish health system, the national guidance recommends that incremental health gains from intervention over TAU be expressed as Quality-Adjusted Life Years (QALYs), and all costs relevant to a health and social care budget should be considered. To be considered cost effective, the incremental cost effectiveness ratio of HSCP plus usual ED care, compared to usual ED care alone, would need to demonstrate producing health gain for less than the cost-effectiveness threshold, which is currently set at $45,000 per QALY in Ireland.

Economic evaluations of ED models of care have been shown, through systematic searches, to be largely absent in the evidence base. This paper reports cost-effectiveness analysis, conducted alongside the OPTI-MEND trial, with a view to informing Irish decision-makers on whether routinely allocating HSCP teams, that provide early assessment and intervention for low urgency older people, represents value for money, compared to TAU.

SECTION: METHODS
Methods

All methods regarding the conduct of this economic evaluation conducted alongside the OPTI-MEND trial were described in a Health Economic Analysis Plan.

Trial design

A single-cent

A single-centre, parallel group, randomised controlled trial was conducted in the ED of a regional university teaching hospital in the Mid-West of the Republic of Ireland. The trial was registered on ClinicalTrials.gov (NCT03739515) and a protocol detailing the clinical- and cost-effectiveness analyses were published in advance. The study received ethics approval from the Health Service Executive (HSE) Mid-Western Regional Hospital Research Ethics Committee on 20th September 2018 (Ref: 103/18).

Participant inclusion followed specific eligibility criteria described in Table 1. Recruitment of participants took place between December 2018 and May 2019. After giving written consent to take part, each participant underwent a baseline assessment and were then randomly allocated to the intervention or control group. A total of 353 older people aged =65 years were randomised to either receive HSCP plus TAU (n = 176), or TAU (n = 177). Full details on patient inclusion criteria are described elsewhere.

SECTION: TABLE
Eligibility criteria of trial participants at enrolment.

Inclusion criteria Exclusion criteria Aged =65 years Aged under 65 years MTS 3-5 MTS 1-2* Off baseline mobility and functional status Neither the patient nor the carer can communicate in English sufficiently to complete informed consent or baseline assessment Capacity and willingness to provide informed consent Lacking capacity to provide informed consent ** Presenting during HSCP operational hours (8am-5pm Monday-Friday) Presenting outside HSCP operational hours (5pm-8am or on Saturday/Sunday) Presenting with any of the following complaints, as per Manchester Triage System:Before medical work-up: Limb problems; Falls; Unwell adult; Back pain; Urinary problems, or Ear and facial problems Presenting with complaints other than described in the inclusion list.

MTS = Manchester Triage System.

* MTS score 1-2 only recruited after Emergency Medicine diagnostic work-up and suitability for HSCP assessment determined.

**In cases where there was a clinical concern regarding capacity to consent, the 4AT tool was used to screen for cognitive impairment and in participants where there was evidence of moderate-profound impairment, the patient's nominated contact person was contacted for consent.

SECTION: METHODS
The research nurse (CD) who conducted the evaluations was blind to group allocation. Only the research nurse and the HSCP team had access to information that could identify the participants during data collection. Once all data were collected, data were anonymised and the final dataset that was used for analysis contained no identifiable information.

Intervention and control groups

To create the HSCP team, three full-time senior healthcare professionals were employed and allocated to work in the ED: one physiotherapist, one occupational therapist and one medical social worker, all at senior level. Participants who were eligible to be seen by the HSCP team were identified either through the ED triage system, or via consultation with the Emergency Medicine staff. The control group received treatment as usual (TAU) chosen because it represented routine ED care that patients would ordinarily receive on attendance at the ED and allowed incremental cost effectiveness analysis.

Cost required to provide HSCP team

To inform the cost of the intervention within the base-case cost-effectiveness analysis, the OPTI-MEND trial budget for allocating the HSCPs, over TAU, were utilised. The average cost per participant was calculated as the total budget divided by the number of trial recipients.

Resource use and associated costs

In addition to considering the cost of providing a HSCP team in the ED, and determining how this compares to TAU, resource use data were collected from all participants by a trained research nurse blind to group allocation. Resource use data was gathered from the hospital database of service use following discharge and included number of visits (if any) to the General Practitioner (GP), public health nurse, home help/home support, private consultations, outpatient department visits, and allied health service use.

The economic evaluation sought to examine wider resource use, and the associated cost, both immediately following the ED index visit, and in the interval between the two successive trial follow-up timepoints (30-days and 6-months). Immediately following presentation to the ED, time from ED registration to discharge was measured in hours and, where participants were admitted as inpatients, their length of inpatient stay was captured. Participants were also followed up at 30 days after their index visit to ED and the number of unscheduled ED re-visit and, where applicable, length inpatient stay, were captured. The final follow-up was conducted approximately 6 months after the index visit and individuals resource use after the date of their 30-day follow up was captured and reported unscheduled ED re-visit, inpatient length of stay, outpatient contact and community contacts (specifically with either general practitioner, nurse, physiotherapist, occupational therapist, dietician, or podiatrist).

For all items of resource use captured, a related Irish Unit Cost was identified (see Table 3) and, for each participant, the quantity of each resource item was multiplied by the related Irish Unit cost.. Summing all individual costs, a total cost per participant was calculated and, by adding the incremental cost related to their intervention group (HSCP + TAU or TAU), a group average total cost, relevant from the perspective of the wider healthcare system, was calculated. Formally, the Total Cost equation is:

For each arm of the study, the average use of each resource, the associated average cost per item and the total average cost are summarised.

Health outcomes for economic evaluation

Participants' responses to the EQ-5D-5L questionnaire were used to estimate health states utilities using the Irish value set. Using an area-under-the-curve approach, the estimated health state utility at each timepoint and the specific dates of data collection, Quality-Adjusted Life Years (QALYs) were estimated across all timepoints.ts' responses to the EQ-5D-5L questionnaire were used to estimate health states utilities using the Irish value set. Using an area-under-the-curve approach, the estimated health state utility at each timepoint and the specific dates of data collection, Quality-Adjusted Life Years (QALYs) were estimated across all timepoints.

Cost-effectiveness analysis

Unadjusted Incris

Unadjusted Incremental Cost Effectiveness Ratio (ICER) for each intervention group are calculated compared to treatment as usual (TAU) using the following formula: where is the average total costs and is the average effect, expressed in terms of Quality-Adjusted Life Years.

To account for the joint distributions of cost and QALYs, the differences between groups were estimated using Zellner (1962) Seemingly Unrelated Regression Equation (SUR), the differences between groups were estimated using Zellner (1962) Seemingly Unrelated Regression Equation (SUR); SUR is selected as it is considered more efficient over unrelated ordinary least suare regression and reports correlation between costs and effects. Non-parametric bootstrapping (10,000 replication) was conducted on random samples of the observed data and the results of the bootstrap are presented as a scatter plot on the cost effectiveness plane. Furthermore, joint distribution of costs and outcomes were illustrated using 50%, 75% and 95% confidence ellipses surrounding the ICER, indicating on the CE plane, the probability space within which we are confident the true ICER is found.

Guidelines for the Economic Evaluation of Health Technologies in Ireland require that probability analysis present "the probability of an ICER is being below $20,000 and $45,000 per QALY, respectively". Where relevant, the probability of HSCP being cost-effective at these willingness-to-pay thresholds were calculated and how the probability of HSCP being cost effective increases as willingness-to-pay increases, a cost effectiveness acceptability curve (CEAC) is generated. No discounting was applied as the study was less than 12 months in duration.No discounting was applied as the study was less than 12 months in duration.

Patient and public involvement

The design and implementation of the trial was informed by extensive consultation with key ED stakeholders, including ED patients and caregivers, as well as hospital and ED medical, nursing and HSCP staff.

SECTION: RESULTS
Results

Inspection of baseline characteristics indicated that trial randomisation produced well balanced groups across most characteristics and that the trial was sufficiently powered for cost effectiveness analysis.

The Consolidated standards of reporting trials (CONSORT) diagram was adapted to report key variables and explain the sample available for complete case cost-effectiveness analysis (see Fig 1). Overall, OPTI-MEND randomised 353 participants to either HSCP + TAU (n = 177) or TAU (n = 176) and all participants completed the intervention. For complete case cost effectiveness analysis, missing responses to EQ-5D-5L and/or dates for this data or missing health care use data (HCU) resulted in omission from the final analysis. Attrition at either the 30-day or 6-month follow-up was documented as either lost to follow up or participants discontinued in the study. For participants who died during the study, where the date of death was obtained, they were reported as "deaths" between the timepoint and were included in the complete case analysis (i.e., their health utility and health care use being zero on the date of death onwards).

SECTION: FIG
CONSORT 2010 flow diagram.

In contrast the clinical effectiveness analysis, this diagram specifically explains data available for use in complete case cost effectiveness analysis.

SECTION: RESULTS
With reference to trial budgets, the HSCP team were employed for a period of six months as part of the OPTI-MEND trial study at a cost of $118,792.89 for the duration of the trial. A budget of $7,500 was allocated to cover cost of aids and appliances for participants during the intervention and a dedicated assessment room in the ED for $14,600 for the six-month period. This total required budget was $140,892.89.

To calculate individuals cost related to their health care use, Table 2 provides the unit costs use to convert resource usage into costs.

SECTION: TABLE
Unit costs (in 2019 $ prices).

Resource use items Unit cost ($) Sources HSCP intervention $800.53 See Appendix 1 Cost associated with consequences of HSCP intervention Average cost of ED admission $264.98 See Appendix 2 Cost per patient hour in ED $14.63 See Appendix 2 Inpatient elective stay: (national average per night) $933.00 Gillespie (2022) Inpatient emergency stay (national average per night) $933.00 Gillespie (2022) Outpatient consultation (average cost) $136.00 Gillespie (2022) General Practitioner appointment $60.00 Gillespie (2022) Nurse $56.00 Smith (2021) Physiotherapist $65.00 Smith (2021) Occupational Therapist $65.00 Smith (2021) Dietician $60.00 Smith (2021) Podiatrist $65.00 Smith (2021)

SECTION: RESULTS
Table 3 reports, by treatment group, the average health care use (left) and associated cost (right) for all resource use items obtained in the trial.

SECTION: TABLE
Unadjusted resource use, and associated costs, by treatment group (Source: Medical records).

Healthcare Resource items (by timepoint) Resource use Associated costs HSCP TAU HSCP TAU Mean Sd n Mean sd n Mean ($) sd ($) n Mean ($) sd ($) n Baseline: HSCP team intervention 1 0 177 0 0 177 801 0 176 0 0 177 ED length of stay (hours) 11.502 12.729 176 18.113 19.414 177 168 186 176 265 284 177 Hospital length of stay (days) 2.119 6.068 176 9.322 15.677 177 1,977 5,662 176 8,697 14,626 177 30-day follow up: Number of unscheduled ED re-visit 0.222 0.526 176 0.169 0.47 177 59 139 176 45 125 177 Inpatient admission: length of stay (days) 1.159 4.028 176 1.373 4.808 177 1,081 3,758 176 1,281 4,486 177 6-month follow up: Number of unscheduled ED re-visit 0.301 0.571 176 0.367 0.704 177 80 151 176 97 186 177 Inpatient admission 1: length of stay (days) 1.812 7.145 176 2.068 5.848 177 1,691 6,666 176 1,929 5,456 177 Inpatient admission 2: length of stay (days) 0.415 2.741 176 0.531 2.518 177 387 2,557 176 495 2,349 177 Inpatient admission 3: length of stay (days) 0.193 2.563 176 0.102 1.353 177 180 2,391 176 95 1,262 177 Outpatient appointments 0.835 1.261 176 1.017 1.653 177 114 171 176 138 225 177 Community contacts: General Practitioner 1.864 2.41 176 1.565 2.288 177 112 145 176 94 137 177 Community contacts: Nurse 1.08 3.673 176 1.729 5.745 177 60 206 176 97 322 177 Community contacts: Physiotherapist 0.875 2.52 176 0.424 1.351 177 57 164 176 28 88 177 Community contacts: Occupational Therapist 0.097 0.333 176 0.141 0.619 177 6 22 176 9 40 177 Community contacts: Dietician 0 0 176 0.006 0.075 177 0 0 176 0 5 177 Community contacts: Podiatrist 0.091 0.457 176 0.056 0.409 177 6 30 176 4 27 177 Total cost - - - - - - $6,779 $12,083 176 $13,275 $16,976 177

SECTION: RESULTS
Table 4 reports the average and 95% Confidence Intervals for each timepoint, unadjusted utilities and costs by timepoint, and across the whole study, QALY and total costs and between group difference of QALYs and Total Cost. The difference in QALYs and Total Cost were subject to bootstrapping (10,000 replication) to provide unbiased 95% confidence intervals and finds the unadjusted between-group difference in QALYs is 0.053 (bootstrapped 95% CI: 0.019 to 0.086) and in total cost -$6,128 (bootstrapped 95% CI: -$9,180 to -$3,075).

SECTION: TABLE
Mean (95% Confidence Intervals) for unadjusted utilities and costs (by timepoint), QALY and total costs (across all timepoints) and between group difference of QALYs and total cost.

Timepoint HSCP TAU Between group difference Costs Outcomes Costs Outcomes Baseline $2,741 ($1,909 to $3,574) 0.484 (0.428 to 0.54) $8,203 ($6,171 to $10,235) 0.484 (0.426 to 0.542) - 30-day $1,170 ($563 to $1,777) 0.7 (0.65 to 0.75) $1,440 ($710 to $2,169) 0.623 (0.561 to 0.684) - 6-months $2,725 ($1,364 to $4,087) 0.773 (0.73 to 0.817) $3,122 ($1,995 to $4,249) 0.701 (0.644 to 0.758) - QALY* - 0.344 (0.323 to 0.364) - 0.291 (0.264 to 0.317) 0.053 (0.019 to 0.086) Total cost* $6,637 ($4,746 to $8,528) - $12,764 ($10,344 to $15,185) - -$6,128 (-$9,180 to -$3,075)

* Bootstrapped 95% confidence intervals (10,000 replications).

SECTION: RESULTS
To model the joint distribution of costs and QALYs for incremental cost effectiveness analysis of HSCP, and to control for baseline utility, seemingly unrelated regression was performed on the n = 322 complete cases available across all time points. Regression of the joint distribution find that total costs and QALYs were significantly correlated, and treatment group explained a large proportion of the variance in QALY (R2 = 0. 2442) and a smaller proportion of the variance in total cost (R2 = .0448). Correlation between Total Cost and QALYs was -0.2803 and negative correlation indicates individuals with worse outcomes have higher costs. Accounting for correlation in the joint distribution, the dedicated HSCP intervention reduced total cost to healthcare by $6,128 (95% CI: -$9,217 to -$3,038, p0.001) and resulted in an incremental QALY of 0.0529 (95% CI: 0.0231 to 0.0826) (see Table 5).

SECTION: TABLE
Seemingly unrelated regression of cost and QALYs, controlling for baseline utilities (n = 322).

Variables Total cost (HSE perspective, $, 95% C.I.) QALY (95% CI) Treatment -$6,128 (-$9,217 to -$3,038) *** 0.0529 (0.0231 to 0.0826) *** Baseline utility 0.1821 (0.1431 to 0.2211) *** Constant $12,764 ($10,594 to $14,935) *** 0.2026 (0.1745 to 0.2308) ***

R2(Total Cost): 0.0448; R2(QALY): 0.2442; Correlation matrix of residuals of Total Cost and QALYs: -0.2803; Breusch-Pagan test of independence: chi2(1): 25.303***.

Significance levels: ***: p 0.001; **: p 0.005.

SECTION: RESULTS
Fig 2 illustrates results from the analysis of the uncertainty of the joint distribution of total cost and QALY. As the majority of bootstrapped replicates call in the bottom right quadrant, this indicates that HSCP has a 99.85% certainty that HSCP + TAU dominates (i.e. is more effective and saves money) over TAU alone suggesting a high probability the intervention should replace the usual arrangement of care.

SECTION: FIG
Cost-effectiveness plane showing uncertainty in the joint distribution of cost and QALYs that surround the incremental cost-effectiveness ratio (ICER).

SECTION: RESULTS
Impact of patient and public involvement

Qualitative insights gathered during the consultation identify enablers and challenges associated with the introduction of the HSCP team and the trial data collection.

SECTION: DISCUSS
Discussion

The OPTI-MEND trial was performed on the hypothesis that, early assessment and intervention for low urgency older people can facilitate shorter stays in the ED, reduces risk of hospital admissions and improve satisfaction with overall care. Analysis of clinical effectiveness demonstrated such HSCP teams significantly reduce ED LoS, and incidence of hospital admissions and, building upon these initial findings, this formal cost-effectiveness analysis now confirms the magnitude of potential cost savings the Irish health system, as well as significant improvement in health.

The economic evaluation conducted alongside the OPTI-MEND trial firstly estimates that the average cost of a contact with the HSCP team during ED admission is $801. In line with HIQA guidance from the Economic Evaluation of Health Technologies in Ireland require that probability analysis present "the probability of an ICER is being below $20,000 and $45,000 per QALY, respectively". Because of contact with HSCP team, there is an average incremental saving in the total cost, compared to TAU, of -$6,128 per patient, largely driven by averting inpatient admission and stay. As effectiveness analysis show an average benefit of 0.053 additional per QALYs and given the treatment results in overall cost saving, there is certainty from OPTI-MEND data that, HSCP teams are cost effective and may in fact 'dominate' usual care (i.e. that is would be efficient use of resource to replace the current arrangement of care in the subpopulation).

The OPTI-MEND trial has shown that a dedicated ED-based HSCP team, as compared to TAU, has positive clinical outcomes that allow a higher use of services for more populations (e.g. by reducing inpatient length of stay, lower rates of hospital admission) and a high reduction in cost per patient. From this analysis, we can reliably conclude that HSCP represents value to the Irish health system and should be adopted as part of treatment as usual in Irish EDs. While these dedicated HSCP teams are currently in situ across the majority of ED in Ireland, further work is ongoing to establish core standards of care across these teams.

The study was carried out on data collected in one setting within the Irish context and the results may not be generalisable to other contexts where healthcare infrastructure, processes and costs may be different.

SECTION: SUPPL
Supporting information

SECTION: ABBR
Abbreviations

ADL

Activities of daily living

CEA

Cost-effectiveness analysis

CEAC

Cost-effectiveness acceptability curve

CEP

Cost-effectiveness plane

CI

Confidence Interval

CONSORT

Consolidated standards of reporting trials

ED

Emergency department

GP

General practitioner

HCU

Healthcare use

HSCP

Health and Social Care Professional

HSE

Health Service Executive

ICER

Incremental cost-effectiveness ratio

LoS

Length of Stay

MTS

Manchester triage system

QALY

Quality-adjusted life year

TAU

Treatment as usual

SECTION: REVIEW_INFO
Author response to Decision Letter 0

9 Jan 2024

To ensure that all comments were thoroughly addressed, and for ease of access for reviewers and editors of how these were have been addressed, please see my notes below (ie DT NOTES).

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DT NOTES: The above style requirements have been checked and adjusted in line with each point

2. Please ensure that you refer to Figure 2 in your text as, if accepted, production will need this reference to link the reader to the figure.

DT NOTES:

o "Figure 2" had been referred to in the original article. However, it was noted this text has not been inserted as a cross-reference so did not hyperlink to figure - this has now been updated.

3. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 5 in your text; if accepted, production will need this reference to link the reader to the Table.

DT NOTES:

o The paragraph relating to results of seemingly unrelated regression now concludes to point the read to the table of results by saying "(see Table 5)."

4. 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.

DT NOTES:

o Reference list from 1 to 15 are all complete and correct and I do not find any need to retract or remove any references.

o I have noted an issue with reference manager from my former researcher of different software and have addressed this by ensuring all citation were included using Endnote. All former references were removed and replacedin the required style

o I note that reference to the primary paper (ie reference 3) was cited multiple in the body text and therefore are superfluous to need and are therefore retracted. The one exception that is kept is the citation in Figure 1 as it is felt this is vital to clarifying differences between complete case analyses between the clinical and cost effectiveness papers

o I also note that reference to Zellner 1962 paper on 'seemingly unrelated regression' is missing and is now added (appears now at reference 9 making a total of 16 references). This omission also addresses query by one reviewer (see later comment regarding this reviewer comment).

o Also, references to sources of costs (Table 2) were missing and now figure as reference 18 (Gillespie 2022) and 19 (Smith 2021).

o Finally, in line with PLOS instructions on referencing style, Endnote style was set to 'Vancouver'. However, contrary Plos "MANUSCRIPT BODY FORMATTING GUIDELINES" where is state "Cite references in brackets (for example, "[1]" or "[2-5]"or "[3,7,9])", please note Vancouver appears with round brackets. As such, Endnote template for Vancouver has been adjusted (see link).

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.

DT NOTES:

o Changes to refences are given in detail here and referenced in the letter. The citation list is now 100% accurate

Additional Editor Comments:

This study aims to evaluate and compare whether augmenting the treatment as usual for older adults admitted to ED is cost-effective based on the Cost-effectiveness analysis (CEA). The CEA is sound, though the use of statistical methods and regression must be justified.

DT NOTES:

o The comment on statistical methods (Zellner 1962 seemingly unrelated requestions) was missing.

o In relation to the reviewer comment (ie "Seemingly unrelated regression must be justified as more advanced approaches have been proposed since Zellner's seminal paper"), I further add an explanatory text

o

o ... article of the statistical approach in Health Economics (see Willan 2004, citation 16) and more recent article entitled 'The statistical approach in trial-based economic evaluations matters: get your statistics together" (see citation 17)

o Finally, for complete clarify, under results I emphasise how the correlation from the residual matrix can be interpreted by adding "Correlation between Total Cost and QALYs was -0.2803 and negative correlation indicates individuals with worse outcomes have higher costs."

In addition, it is better to attach the protocol in appendix if any.

DT NOTES:

o There is a published trial protocol which is referenced (see citation number 12)

o Furthermore, as per requirements (see CHEERS checklist) a Health Economic Analysis Plan was also peer reviewed and published (see citation 11).

10.1371/journal.pone.0298162.r003

Decision Letter 1

Wong

Arkers Kwan Ching

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

22 Jan 2024

The Cost Effectiveness of Early Assessment and Intervention by a Dedicated Health and Social Care Professional Team for Older Adults in the Emergency Department Compared to Treatment-As-Usual: Economic Evaluation of the Opti-Mend Trial

PONE-D-23-13587R1

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10.1371/journal.pone.0298162.r004

Acceptance letter

Wong

Arkers Kwan Ching

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

13 Jun 2024

PONE-D-23-13587R1

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