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Open research questions in Health Systems, Economic Evaluations, Quality of Life

54 unresolved questions extracted from the limitations and future-work sections of 748 Health Systems, Economic Evaluations, Quality of Life papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Background Methamphetamine‐associated heart failure (MethHF) is an aggressive HF subtype, and its economic impact on the US health care system is not well defined.

    Development and Validation of a Markov Microsimulation Model for the Economic Evaluation of Methamphetamine‐Associated Heart Failure in the United States · 2026 · DOI

  • Conclusion Policy factors, particularly reimbursement amount, likely play a role in SDF utilization; however, additional research is needed to understand how dentists adopt SDF in ways that translate into improved outcomes.

    Examining Associations Between Medicaid Policy and Silver Diamine Fluoride Utilization · 2026 · DOI

  • This study has several important limitations that should be considered when interpret- ing the findings. First, the analysis is cross-sectional and observational in nature, relying on aggregated country-level data from a single time point. Second, no causal identifica- tion strategy or experimental design is employed; therefore, the reported associations should not be interpreted as causal effects. While we control for multiple confound- ing variables and use anomaly-aware weighting, unmeasured confounders and reverse causality cannot be ruled out. Third, the findings represent predictive relationships and hypothesis-generating insights rather than definitive evidence for policy interventions. Future research employing longitudinal data, quasi-experimental designs, or random- ized controlled trials would be necessary to establish causal mechanisms.

    Explainable machine learning analysis of medicine pricing and life expectancy across countries · 2026 · DOI

  • Paid labour: Use FCA for lost paid work time in the reference case (societal perspective). Unpaid labour: The opportunity cost approach is recommended. Researchers should be aware of and transparent about any equity implications, but ultimately the estimated opportunity cost should reflect the decision-maker’s equity position. Leisure Time: Lost leisure time is not to be measured. Other methods may be used in non-reference case analyses.

    Measuring, Valuing, and Incorporating Patient and Caregiver Productivity Costs in Economic Evaluations: A Scoping Review and Environmental Scan · 2026 · DOI

  • Data elements related to comorbidities, concomitant therapies, patient‐reported outcome measures (PROMs), resource use, and safety outcomes were lacking partly or completely in all evaluated registries, highlighting the importance of developing disease‐specific core datasets to which registry holders can benchmark their data collection.

    Repurposing Registries: Completeness of Real‐World Data for Regulatory and <scp>HTA</scp> Purposes in Three Cancer‐Focused Registries · 2026 · DOI

  • Across 409 bill‐level equity impact ratings derived from 296 final REIAs from 2021 to 2024, nearly half of REIAs (46%) indicated that proposed legislation would likely advance racial equity, 9% signaled potential adverse effects, 10% were neutral, and one‐third were inconclusive or negligible.

    Racial Equity Impact Assessments as Tools for Advancing Population Health and Equity in Local Policy · 2026 · DOI

  • 1) to develop a CMV prophylaxis protocol for lung transplant recipients using PubMed- indexed references without AI “hallucinations,” which has been a key limitation in other settings.

    Updating CMV protocols in lung transplant patients: a single-center case study modeling use of generative AI for antimicrobial stewardship protocol development and economic impact analysis · 2026 · DOI

  • implementation strategies within Singapore’s healthcare system. cost-containment future design and of actionable support insights inform the to 4.1 Sample characteristics The effective sample comprised 2,955 healthcare users (aged 65 years and above) with reported medical expenditure, with a mean age of 74.2 years. Approximately 58% were female and 59% were retirees. Total medical expenditure was highly rightskewed (mean: US$7,290.2; SD: 11,990.8; maximum: US $125,610), indicating substantial cost variability among older adults. More than 80% of participants had at least one chronic condition, and over 60% had multiple conditions. Over 59% had supplemented private insurance. About 29% had suffered injuries. In addition, 43.6% reported physical limitations and 28.8% reported activity limitations. These findings underscore the strong association between chronic disease burden, functional impairment, and elevated medical expenditure among the elderly population. 4.2 Empirical results The OLS regression showed that the number of chronic conditions (totchr) was significantly associated with total medical expenditure (estimated β ≈ 1,814.40, p < 0.001). Other things being equal, a one-unit increase in the number of chronic conditions was associated with an approximate $1,844 increase in medical expenditure. Age, gender, injury, activity limitations, and physical limitations were also statistically significant. Diagnostic tests revealed heteroscedasticity and pronounced right-skewness the use of heteroscedasticity-robust standard errors and robust regression to assess sensitivity. These analyses consistently confirmed the central role of chronic conditions. The robust regression estimated with IRLS also yielded a significant effect in totchr (estimated β ≈ 811.30, p < 0.001) after down-weighting the outliers. Compared with OLS, estimates were substantially smaller, indicating that a small number of highcost observations had strongly influenced mean-based estimates. expenditure, prompting robust in To accommodate the strictly positive and right-skewed distribution of medical expenditures, a Gamma-distributed GLM with a log link was estimated. It confirmed the key finding that the number of chronic conditions remained a significant variable of medical costs. to applied identify FMM was subsequently latent subpopulations. Based on Bayesian Information Criterion (BIC) minimisation, a parsimonious two-component model was selected, thus distinguishing a low-expenditure group from the high-expenditure group. The high-cost group comprised older adults, and individuals with more chronic conditions. This classification provides useful insights for designing targeted and cost-effective intervention strategies in Singapore. that marginal medical costs Nonparametric kernel regression using the Epanechnikov kernel demonstrated increase progressively with the number of chronic conditions. This pattern was corroborated by the Exponential Mean Model (EMM), which suggests that medical expenditure may escalate nonlinearly, potentially rising exponentially once individuals reach a critical threshold of approximately three to four chronic conditions. These findings highlight the compounding financial impact of multimorbidity and underscore the importance of early preventive intervention to mitigate cost acceleration. Building upon the statistical analyses, CART identified physical the primary splitting variables. However, compared with other methods, CART was more prone to overfitting and exhibited limited predictive stability. Reducing variance and demonstrating strong predictive performance, RF regression with 50 trees and 5-fold crossvalidation identified income, activity limitation, age, and chronic conditions as key predictors of medical expenditure. limitations and income as for the GBR achieved the highest overall predictive accuracy. It was implemented with Gaussian log-transformed loss expenditure outcome. The model was trained using 80% of the data, with 20% reserved for validation. A maximum of 1,000 boosting iterations were allowed. Stochastic gradient boosting was applied with a subsampling rate of 0.5 to reduce overfitting.

    Closing the implementation-evidence gap using data science: a transferable workflow applied to medical cost analysis · 2026 · DOI

  • The study has important limitations. First, the quantitative phase relied on a moderate nonprobability sample, which for statistical exploratory PLS-SEM but generalisability. The respondent profile was also relatively young and not to HTA specialists, so the results should be read as organisation-level perception evidence rather than as a census of expert judgement. Second, is cross-sectional and the research therefore captures perceptions at one point in time rather than the evolution of HTA maturity. Third, the setting is confined to Saudi private healthcare, so transferability to public systems or other countries should be made carefully. Fourth, downstream construct proximity remained high, with correlations of 0.9014 between AQD and EDM and 0.9317 between SEHTA and EDM, and selected HTMT inspections were borderline; the same-source survey design also means commonmethod inflation cannot be ruled out. The structural findings should therefore be interpreted as strong explanatory patterns rather than as final causal proof. This is particularly relevant when considering the high R² for EDM. Fifth, the qualitative strand was designed for explanation representativeness.

    AI-ENABLED HEALTH TECHNOLOGY ASSESSMENT AS AN ORGANISATIONAL CAPABILITY SYSTEM: MIXED-METHOD EVIDENCE FROM SAUDI PRIVATE HEALTHCARE · 2026 · DOI

  • Our study encountered several strengths. First, we used the cTTO data from the Jordanian EQ-5D-3L valuation study[25]. Second, our study was representative of the Jor- danian population, and high-quality assurance standards were applied in accordance with the standardized EuroQol EQ-VT v2.1 valuation protocol [15, 16]. Furthermore, we collected not only socioeconomic characteristics but also information on health-related indicators, such as smoking and exercise. On the other hand, we have encountered several limita- tions: representativeness is tied to what is known and mea- surable. Our quota sampling did not include employment, education, and marital status as stratification factors in addi- tion to geographical region, age, and gender. In addition, we agree with van Nooten et al. (2018) that there is a need to systematically investigate the impact of respondents’ socio- demographics on cTTO health state valuation by designing a focused study with larger sample sizes rather than using by-product data from valuation studies [19]. Despite this Quality of Life Research (2026) 35:154 1 3 154 Page 10 of 12 limitation, future valuation studies in Jordan can benefit from this study in sampling planning. Another limitation may be the respondent’s understand- ing of exercise. We kept it a general question, without dif- ferentiating between going to the gym or engaging in any physical activity, such as walking. We did not ask about the number of family members in a household or the number of children per family, even though previous studies have shown these variables to be predictors of health state valu- ations [19, 64].

    Factors associated with health state valuations: a secondary analysis of an EQ-5D-3L valuation study from Jordan · 2026 · DOI

  • Hence, further investigation into refining PS-or exploration of another approach-appears warranted for operationalising the equity-efficiency trade-off.

    Looking back and moving forward: On the application of proportional shortfall in healthcare priority setting in the Netherlands · 2018 · DOI

  • TDABC is applicable in health care and can help to efficiently cost processes, and thereby overcome a key challenge associated with current cost-accounting methods The method's ability to inform bundled payment reimbursement systems and to coordinate delivery across the care continuum remains to be demonstrated in the published literature, and the role of TDABC in this cost-accounting landscape is still developing.

    Time-driven activity-based costing in health care: A systematic review of the literature · 2017 · DOI

  • CONCLUSIONS: While the evidence is sufficient to conclude that there is burden associated with IRB review, it is too limited to allow for valid estimates of its magnitude or to serve as the basis for formulating policies on IRB reform.

    Burdens on Research Imposed by Institutional Review Boards: The State of the Evidence and Its Implications for Regulatory Reform · 2011 · DOI

  • Despite medical care expenditures that are the highest of any industrialized nation, deficiencies in the way health information is collected and a lack of agreement on the best indicators by which to measure progress are hindering efforts to improve Americans’ health, according to a new national report.

    Report: Better measurement can improve U.S. health outcomes · 2011

  • Contrary to what some critics of the approach have advocated, however, prudent use of scarce research resources is not simply to study conditions with a high disease burden in the host country, and therefore to prefer research on HIV or malaria over research on Burkitt's lymphoma.

    The Fair Benefits Approach Revisited · 2010 · DOI

  • Data from the UK studies also suggests there is currently insufficient evidence to support the general health outcome, Quality Adjust Life Years (QALYs) measure recommended by UK regulatory authorities to serve as a main individual drug user outcome.

    Using Economic Evaluation Techniques to Inform Policy: Reflections from Some UK Studies · 2008 · DOI

  • Addressing the open questions, this Article urges that the principles should ordinarily be taken as mandatory, not merely permissive; that agencies may reject them in certain identifiable circumstances; and that steps should be taken toward quantitative analysis of the effects of regulation, designed to discipline the relevant inquiries.

    Cost-Benefit Default Principles · 2001 · DOI

  • Higher preoperative patient optimism is a consistent predictor of improved HRQoL for both TSA patients and ream-and-run arthroplasty patients, and further study on optimizing the influence of patient expectations and optimism may be warranted.

    Credit, investment and economic cycles in the caribbean · 1999 · DOI

  • Rwanda has implemented several innovative surveillance programmes, but a synthesis of methodological approaches for assessing their cost-effectiveness is lacking.

    A Systematic Review of Methodological Frameworks for Evaluating the Cost-Effectiveness of Public Health Surveillance Systems in Rwanda: Evidence from Randomised Field Trials · 2026 · DOI

  • { "background": "Public health surveillance is a cornerstone of effective health systems, yet rigorous economic evaluations of such systems in low-resource settings are scarce.

    A Systematic Review of Methodological Frameworks for Evaluating the Cost-Effectiveness of Public Health Surveillance Systems in Rwanda: Evidence from Randomised Field Trials · 2026 · DOI

  • Despite increasing recognition of EDS, little is known about its economic burden in the United States.

    Understanding Ehlers-Danlos Syndrome: A Claims-Based Analysis of Healthcare Cost Patterns · 2026 · DOI

  • Abstract Introduction General health checks (GHCs) are widely used for disease prevention, however, their clinical effectiveness, psychological impact, and economic value remain debated.

    Effectiveness and cost-effectiveness of general health checks in adults: A systematic review · 2026 · DOI

  • Concensus on valuation 418 methods is lacking: the HCA is simple but overestimates, the FCA is conceptually stronger but 419 data-intensive.

    Measuring, Valuing, and Incorporating Patient and Caregiver Productivity Costs in Economic Evaluations: A Scoping Review and Environmental Scan · 2026 · DOI

  • Future research should focus on extending and developing standardized approaches for quantifying dissimilarity between populations and validating transportability methods against pro- spectively collected data.

    Transportability Analyses in Comparative Effectiveness Research: A Conceptual Framework and Methodological Principles Endorsed by the <scp>I</scp> nternational <scp>S</scp> ociety for <scp>P</scp> harmacoepidemiology · 2026 · DOI

  • Our analysis shows a lack of consensus on the impact of each goal and on the concept of a balance between the goals, and a paucity of literature related to the pursuit of the Triple Aim at the health system level.

    Improving the value of healthcare systems using the Triple Aim framework: A systematic literature review · 2022 · DOI

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54 open questions have been extracted from the limitations and future-work passages of 748 Health Systems, Economic Evaluations, Quality of Life papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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