Methodological challenges and potential solutions for economic evaluations of palliative and end-of-life care: A systematic review

Background: Given the increasing demand for palliative and end-of-life care, along with the introduction of costly new treatments, there is a pressing need for robust evidence on value. However, comprehensive guidance is missing on methods for conducting economic evaluations in this field. Aim: To identify and summarise existing information on methodological challenges and potential solutions/recommendations for economic evaluations of palliative and end-of-life care. Design: We conducted a systematic review of publications on methodological considerations for economic evaluations of adult palliative and end-of-life care as per our PROSPERO protocol CRD42020148160. Following initial searches, we conducted a two-stage screening process and quality appraisal. Information was thematically synthesised, coded, categorised into common themes and aligned with the items specified in the Consolidated Health Economic Evaluation Reporting Standards statement. Data sources: The databases Medline, Embase, HTADatabase, NHSEED and grey literature were searched between 1 January 1999 and 5 June 2023. Results: Out of the initial 6502 studies, 81 were deemed eligible. Identified challenges could be grouped into nine themes: ambiguous and inaccurate patient identification, restricted generalisability due to poor geographic transferability of evidence, narrow costing perspective applied, difficulties defining comparators, consequences of applied time horizon, ambiguity in the selection of outcomes, challenged outcome measurement, non-standardised measurement and valuation of costs as well as challenges regarding a reliable preference-based outcome valuation. Conclusion: Our review offers a comprehensive context-specific overview of methodological considerations for economic evaluations of palliative and end-of-life care. It also identifies the main knowledge gaps to help prioritise future methodological research specifically for this field.


Selection process
8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.
Data items 10a List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

Item # Checklist item
Location where item is reported 10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information. 7 Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.
Effect measures 12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.
Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

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13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. n.a.
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.7 13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

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13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g.subgroup analysis, meta-regression). n.a.
13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.n.a.

Reporting bias assessment
14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). n.a.

Certainty assessment
15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.n.a.

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.

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16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were Figure 1 Section and Topic

# Checklist item
Location where item is reported excluded.

Study characteristics
17 Cite each included study and present its characteristics.
Appendix, Table 4 Risk of bias in studies 18 Present assessments of risk of bias for each included study.n.a.

Results of individual studies
19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.confidence/credible interval), ideally using structured tables or plots. n.a.

Results of syntheses 20a
For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.n.a.Specify the inclusion and exclusion criteria for the review.2 Information sources Specify the information sources (e.g.databases, registers) used to identify studies and the date when each was last searched.

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Risk of bias Specify the methods used to assess risk of bias in the included studies. 2

Synthesis of results
Specify the methods used to present and synthesise results.

Included studies
Give the total number of included studies and participants and summarise relevant characteristics of studies. 2

Synthesis of results
Present results for main outcomes, preferably indicating the number of included studies and participants for each.If meta-analysis was done, report the summary estimate and confidence/credible interval.If comparing groups, indicate the direction of the effect (i.e. which group is favoured).

Limitations of evidence
Provide a brief summary of the limitations of the evidence included in the review (e.g.study risk of bias, inconsistency and imprecision). n.a.

Interpretation
Provide a general interpretation of the results and important implications.2 OTHER Funding Specify the primary source of funding for the review.
Listed in referred protocol and main text

Registration
Provide the register name and registration number.

Table 2 .
The PRISMA for Abstracts Checklist

Table 4 .
Characteristics of included studies 1