An overview of the perspectives used in health economic evaluations.

The term 'perspective' in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders' viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence.

Telemedicine Utilization Patterns and Implications Amidst COVID-19 Outbreaks in Thailand Under Public Universal Coverage Scheme.

During COVID-19 pandemic, telemedicine was a strategy to facilitate healthcare service delivery minimizing the risk of direct exposure among people. In Thailand, the National Health Security Office has included telemedicine services under the Universal Coverage Scheme to support social distancing policies to reduce the spread of COVID-19. This study aimed to determine the patterns of telemedicine service use during major COVID-19 outbreaks including Alpha, Delta, and Omicron in Thailand. We retrospectively analyzed a dataset of telemedicine e-claims from the National Health Security Office, which covers services reimbursed under the Universal Coverage Scheme between December 2020 and August 2022. An interrupted time-series analysis, Pearson correlation analysis and binary logistic regression were performed. Almost 70% of the patients using telemedicine services were over 40 years old. Most patients used services for mental health problems (25.6%) and major noncommunicable diseases, including essential hypertension (12.6%) and diabetes mellitus (9.2%). The daily number of using telemedicine service was strongly correlated with the number of COVID-19 new cases detected. An immediate change in the trend of using telemedicine was detected at the onset of outbreaks along with the surge of infection. The follow-up use of telemedicine services was not substantial among female, older adults patients and those with non-communicable diseases except mental health problems, and infectious diseases. Strategies need to be developed to reinforced healthcare resources for telemedicine during the surge of outbreaks and sustain the use of telemedicine services for chronic and infectious diseases, regardless of the pandemic, and promote the efficiency of healthcare systems.

Durability of the Effectiveness of Heterologous COVID-19 Vaccine Regimens in Thailand: Retrospective Cohort Study Using National Registration Data.

BACKGROUND: The durability of heterologous COVID-19 vaccine effectiveness (VE) has been primarily studied in high-income countries, while evaluation of heterologous vaccine policies in low- and middle-income countries remains limited. OBJECTIVE: We aimed to evaluate the duration during which the VE of heterologous COVID-19 vaccine regimens in mitigating serious outcomes, specifically severe COVID-19 and death following hospitalization with COVID-19, remains over 50%. METHODS: We formed a dynamic cohort by linking records of Thai citizens aged ≥18 years from citizen vital, COVID-19 vaccine, and COVID-19 cases registry databases between May 2021 and July 2022. Encrypted citizen identification numbers were used to merge the data between the databases. This study focuses on 8 common heterologous vaccine sequences: CoronaVac/ChAdOx1, ChAdOx1/BNT162b2, CoronaVac/CoronaVac/ChAdOx1, CoronaVac/ChAdOx1/ChAdOx1, CoronaVac/ChAdOx1/BNT162b2, BBIBP-CorV/BBIBP-CorV/BNT162b2, ChAdOx1/ChAdOx1/BNT162b2, and ChAdOx1/ChAdOx1/mRNA-1273. Nonimmunized individuals were considered for comparisons. The cohort was stratified according to the vaccination status, age, sex, province location, month of vaccination, and outcome. Data analysis employed logistic regression to determine the VE, accounting for potential confounders and durability over time, with data observed over a follow-up period of 7 months. RESULTS: This study includes 52,580,841 individuals, with approximately 17,907,215 and 17,190,975 receiving 2- and 3-dose common heterologous vaccines (not mutually exclusive), respectively. The 2-dose heterologous vaccinations offered approximately 50% VE against severe COVID-19 and death following hospitalization with COVID-19 for 2 months; however, the protection significantly declined over time. The 3-dose heterologous vaccinations sustained over 50% VE against both outcomes for at least 8 months, as determined by logistic regression with durability time-interaction modeling. The vaccine sequence consisting of CoronaVac/CoronaVac/ChAdOx1 demonstrated >80% VE against both outcomes, with no evidence of VE waning. The final monthly measured VE of CoronaVac/CoronaVac/ChAdOx1 against severe COVID-19 and death following hospitalization at 7 months after the last dose was 82% (95% CI 80.3%-84%) and 86.3% (95% CI 83.6%-84%), respectively. CONCLUSIONS: In Thailand, within a 7-month observation period, the 2-dose regimens could not maintain a 50% VE against severe and fatal COVID-19 for over 2 months, but all of the 3-dose regimens did. The CoronaVac/CoronaVac/ChAdOx1 regimen showed the best protective effect against severe and fatal COVID-19. The estimated durability of 50% VE for at least 8 months across all 3-dose heterologous COVID-19 vaccine regimens supports the adoption of heterologous prime-boost vaccination strategies, with a primary series of inactivated virus vaccine and boosting with either a viral vector or an mRNA vaccine, to prevent similar pandemics in low- and middle-income countries.

Mapping the value for money of precision medicine: a systematic literature review and meta-analysis.

Objective: This study aimed to quantify heterogeneity in the value for money of precision medicine (PM) by application types across contexts and conditions and to quantify sources of heterogeneity to areas of particular promises or concerns as the field of PM moves forward. Methods: A systemic search was performed in Embase, Medline, EconLit, and CRD databases for studies published between 2011 and 2021 on cost-effectiveness analysis (CEA) of PM interventions. Based on a willingness-to-pay threshold of one-time GDP per capita of each study country, the net monetary benefit (NMB) of PM was pooled using random-effects meta-analyses. Sources of heterogeneity and study biases were examined using random-effects meta-regressions, jackknife sensitivity analysis, and the biases in economic studies checklist. Results: Among the 275 unique CEAs of PM, publicly sponsored studies found neither genetic testing nor gene therapy cost-effective in general, which was contradictory to studies funded by commercial entities and early stage evaluations. Evidence of PM being cost-effective was concentrated in a genetic test for screening, diagnosis, or as companion diagnostics (pooled NMBs, $48,152, $8,869, $5,693, p < 0.001), in the form of multigene panel testing (pooled NMBs = $31,026, p < 0.001), which only applied to a few disease areas such as cancer and high-income countries. Incremental effectiveness was an essential value driver for varied genetic tests but not gene therapy. Conclusion: Precision medicine's value for money across application types and contexts was difficult to conclude from published studies, which might be subject to systematic bias. The conducting and reporting of CEA of PM should be locally based and standardized for meaningful comparisons.

Can knowledgeable experts assess costs and outcomes as if they were ignorant? An experiment within precision medicine evaluation.

OBJECTIVES: The purpose of this study is to evaluate the validity of the standard approach in expert judgment for evaluating precision medicines, in which experts are required to estimate outcomes as if they did not have access to diagnostic information, whereas in fact, they do. METHODS: Fourteen clinicians participated in an expert judgment task to estimate the cost and medical outcomes of the use of exome sequencing in pediatric patients with intractable epilepsy in Thailand. Experts were randomly assigned to either an "unblind" or "blind" group; the former was provided with the exome sequencing results for each patient case prior to the judgment task, whereas the latter was not provided with the exome sequencing results. Both groups were asked to estimate the outcomes for the counterfactual scenario, in which patients had not been tested by exome sequencing. RESULTS: Our study did not show significant results, possibly due to the small sample size of both participants and case studies. CONCLUSIONS: A comparison of the unblind and blind approach did not show conclusive evidence that there is a difference in outcomes. However, until further evidence suggests otherwise, we recommend the blind approach as preferable when using expert judgment to evaluate precision medicines because this approach is more representative of the counterfactual scenario than the unblind approach.

Cost-effectiveness analysis of typhoid vaccination in Lao PDR.

BACKGROUND: Typhoid vaccination has been shown to be an effective intervention to prevent enteric fever and is under consideration for inclusion in the national immunization program in Lao PDR. METHODS: A cost-utility analysis was performed using an age-structured static decision tree model to estimate the costs and health outcomes of introducing TCV. Vaccination strategies combined with five delivery approaches in different age groups compared to no vaccination were considered from the societal perspective, using the Gavi price of 1.5 USD per dose. The vaccination program was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of 1 GDP per capita for Lao PDR, equivalent to USD 2,535 in 2020. RESULTS: In the model, we estimated 172.2 cases of enteric fever, with 1.3 deaths and a total treatment cost of USD 7,244, based on a birth cohort of 164,662 births without TCV vaccination that was followed over their lifetime. To implement a TCV vaccination program over the lifetime horizon, the estimated cost of the vaccine and administration costs would be between USD 470,934 and USD 919,186. Implementation of the TCV vaccination program would prevent between 14 and 106 cases and 0.1 to 0.8 deaths. None of the vaccination programs appeared to be cost-effective. CONCLUSIONS: Inclusion of TCV in the national vaccination program in Lao PDR would only be cost-effective if the true typhoid incidence is 25-times higher than our current estimate.

Expanding access to high-cost medicines under the Universal Health Coverage scheme in Thailand: review of current practices and recommendations.

BACKGROUND: There has been an increasing demand to reimburse high-cost medicines, through public health insurance schemes in Thailand. METHODS: A mixed method approach was employed. First, a rapid review of select high-income countries was conducted, followed by expert consultations and an in-depth review of three countries: Australia, England and Republic of Korea to understand reimbursement mechanisms of high-cost medicines. In Thailand, current pathways for reimbursing high-cost medicines reviewed, the potential opportunity cost estimated, and stakeholder consultations were conducted to identify context specific considerations. RESULTS: High-income countries reviewed have implemented a variety of pathways and mechanisms for reimbursing high-cost medicines under specific eligibility criteria, listing processes, varying cost-effectiveness thresholds and special funding arrangements. In Thailand, high-cost medicines that do not offer good value-for-money are excluded from the reimbursement process. A framework for reimbursing high-cost medicines that are not cost-effective at the current willingness-to-pay threshold was proposed for Thailand. Under this framework, specific criteria are proposed to determine their eligibility for reimbursement such life-saving nature, treatment of conditions with no alternative treatment options, and affordability. CONCLUSION: High-cost medicines may become eligible for reimbursement through alternative mechanisms based on specific criteria which depend on each context. The application of HTA methods and processes is important in guiding these decisions to support sustainable access to affordable healthcare in pursuit of Universal Health Coverage (UHC).

Cost-effectiveness of alginic acid in combination with proton pump inhibitor for the treatment of gastroesophageal reflux disease in systemic sclerosis patients.

BACKGROUND: Systemic sclerosis (SSc) patients often become refractory to proton pump inhibitors (PPI)-a standard treatment for gastroesophageal reflux disease (GERD)-and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly. OBJECTIVES: We compared the costs and effectiveness of alginic acid plus PPI versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for GERD in SSc patients unsuitable for, or intolerant to, domperidone. METHODS: An economic evaluation using the Markov model was conducted among SSc patients aged between 40 and 65 years with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/day) and being unsuitable for or intolerant to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-year (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used. RESULTS: The ICER for alginic acid plus PPI versus standard treatments was 377 101 THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160 000 THB/QALY (34.68 THB/USD data on 25 May 2023). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66 313 THB per patient, resulting in an overall budget increase of 5 106 101 to 8 885 942 THB compared with the standard treatment. CONCLUSIONS: Alginic acid plus PPI does not represent good value for money compared with the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.

What, Where, and How to Collect Real-World Data and Generate Real-World Evidence to Support Drug Reimbursement Decision-Making in Asia: A reflection Into the Past and A Way Forward.

BACKGROUND: Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators. METHODS: The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/ RWE. RESULTS: All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: (a) sources and types of RWD being used in HTA, and (b) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled. CONCLUSION: The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia.

Analyses of the return on investment of public health interventions: a scoping review and recommendations for future studies.

Return on investment (ROI) analysis is increasingly being used for evaluating the value for money of public health interventions. Given its potential role for informing health policies, it is important that there is a more comprehensive understanding of ROI analysis within the global health field. To address this gap in the literature, we conducted a scoping review of recent research articles reporting an ROI metric for a health intervention within the public sector in any country setting. The database search was limited to literature published in English and studies published between 1 January 2018 and 14 June 2021. Uses and settings where the ROI metric is being applied, key methodological features of the calculations and the types of economic benefits included were extracted. 118 relevant studies were included within this scoping review. We found that ROI analyses of health interventions differed between those that only included fiscal savings (such as prevented medical expenses) and those which incorporated a wider range of benefits (such as monetised health benefits). This highlights the variation in the definition of ROI analyses and supports the finding that ROI analyses are used for a range of different research questions/purposes within the healthcare sector. We also found that the methodologies used in ROI calculations were inconsistent and often poorly reported. This review demonstrates that there is notable variation in the methodology surrounding recent ROI calculations of healthcare interventions, as well as the definition of ROI analysis. We recommend that ROI metrics should be carefully interpreted before they are used to inform policy decisions regarding the allocation of healthcare resources. To improve the consistency of future studies, we also set out recommended use cases for ROI analysis and a reporting checklist.

A systematic literature review of economic evaluation studies of interventions impacting antimicrobial resistance.

BACKGROUND: Antimicrobial resistance (AMR) is accelerated by widespread and inappropriate use of antimicrobials. Many countries, including those in low- and middle- income contexts, have started implementing interventions to tackle AMR. However, for many interventions there is little or no economic evidence with respect to their cost-effectiveness. To help better understand the scale of this evidence gap, we conducted a systematic literature review to provide a comprehensive summary on the value for money of different interventions affecting AMR. METHODS: A systematic literature review was conducted of economic evaluations on interventions addressing AMR. a narrative synthesis of findings was produced. Systematic searches for relevant studies were performed across relevant databases and grey literature sources such as unpublished studies, reports, and other relevant documents. All identified economic evaluation studies were included provided that they reported an economic outcome and stated that the analysed intervention aimed to affect AMR or antimicrobial use in the abstract. Studies that reported clinical endpoints alone were excluded. Selection for final inclusion and data extraction was performed by two independent reviewers. A quality assessment of the evidence used in the included studies was also conducted. RESULTS: 28,597 articles were screened and 35 articles were identified that satisfied the inclusion criteria. The review attempted to answer the following questions: (1) What interventions to address AMR have been the subject of an economic evaluation? (2) In what types of setting (e.g. high-income, low-income, regions etc.) have these economic evaluations been focused? (3) Which interventions have been estimated to be cost-effective, and has this result been replicated in other settings/contexts? (4) What economic evaluation methods or techniques have been used to evaluate these interventions? (5) What kind and quality of data has been used in conducting economic evaluations for these interventions? DISCUSSION: The review is one of the first of its kind, and the most recent, to systematically review the literature on the cost-effectiveness of AMR interventions. This review addresses an important evidence gap in the economics of AMR and can assist AMR researchers' understanding of the state of the economic evaluation literature, and therefore inform future research. Systematic review registration PROSPERO (CRD42020190310).

Using an experiment among clinical experts to determine the cost and clinical impact of rapid whole exome sequencing in acute pediatric settings.

Objective: Evaluate the cost and clinical impacts of rapid whole-exome sequencing (rWES) for managing pediatric patients with unknown etiologies of critical illnesses through an expert elicitation experiment. Method: Physicians in the intervention group (n = 10) could order rWES to complete three real-world case studies, while physicians in the control group (n = 8) could not. Costs and health outcomes between and within groups were compared. Results: The cost incurred in the intervention group was consistently higher than the control by 60,000-70,000 THB. Fewer other investigation costs were incurred when rWES could provide a diagnosis. Less cost was incurred when an rWES that could lead to a change in management was ordered earlier. Diagnostic accuracy and the quality of non-pharmaceutical interventions were superior when rWES was available. Conclusion: In acute pediatric settings, rWES offered clinical benefits at the average cost of 60,000-70,000 THB. Whether this test is cost-effective warrants further investigations. Several challenges, including cost and ethical concerns for assessing high-cost technology for rare diseases in resource-limited settings, were potentially overcome by our study design using expert elicitation methods.

The impact of universal health coverage and COVID-19 pandemic on out-of-pocket expenses in Thailand: an analysis of household survey from 1994 to 2021.

OBJECTIVES: After Thailand achieved Universal Health Coverage (UHC) in 2002, the extent of financial risk protection has not been assessed in the long term, especially after the COVID-19 pandemic. Therefore, this study aims to revisit the impact of UHC on out-of-pocket expenses (OOPE) for health and to descriptively explore the impact of COVID-19 on OOPE. METHODS: This study was a secondary data analysis and used data from the Socio-Economic Survey from 1994 to 2021 in Thailand. The effect of UHC on the percentage of OOPE in total health expenditures (THE) from 1994 to 2019 was investigated with an interrupted time-series analysis. Descriptive analyses of OOPE in absolute value during the COVID-19 were conducted. RESULTS: The percentage of OOPE in THE significantly decreased both before (ß -2.02%; 95% CI: -2.70% to - 1.33%) and during (ß 1.41%; 95% CI: 0.70% to 2.11%) the UHC period. During the pandemic, total household OOPE for medical equipment was found to have rapidly increased from 643 million THB in 2019 to 9.4 billion THB in 2020. CONCLUSIONS: The trend of providing financial risk protection (measured by OOPE/THE) in Thailand continues until 2019. Providing medical equipment in sufficient and equally accessible manners should be prioritized during the future pandemic.

How to model the impact of vaccines for policymaking when the characteristics are uncertain: A case study in Thailand prior to the vaccine rollout during the COVID-19 pandemic.

Thailand faced a dilemma of which groups to prioritise with a limited first tranche of COVID-19 vaccinations in early 2021, at a time when there was low incidence and low mortality in the country. A mathematical modelling analysis was performed to compare the potential short-term impact of allocating the available doses to either the high severity group (over 65-year-olds) or the high transmission group (aged 20-39). At the time of the analysis, there was uncertainty about the precise characteristics of the vaccines available, in terms of their potential impact on transmission and reductions to the severity of infection. As such, a range of vaccine characteristic scenarios, with differing levels of severity and transmission reductions were explored. Using the evidence available at the time regarding severity reduction of infection due to the vaccines, the model suggested that vaccinating high severity group should be the priority if reductions in deaths is the priority. Vaccinating this group was found to have a direct impact on reducing the number of deaths, while the incidence and hospitalisations remained unchanged. However, the model found that vaccinating the high transmission group with a vaccine with sufficiently high protection against infection (more than 70%) could provide enough herd effects to delay the expected epidemic peak, resulting in both case and death reductions in both target groups. The model explored a 12-month time horizon. These analyses helped to inform the vaccination strategy in Thailand throughout 2021 and can inform future modelling studies for policymaking when the characteristics of vaccines are uncertain.

Health economic evaluations for Indonesia: a systematic review assessing evidence quality and adherence to the Indonesian Health Technology Assessment (HTA) Guideline.

Background: The Government of Indonesia implemented health technology assessment (HTA) to ensure quality and cost control in the National Health Insurance Program (Jaminan Kesehatan Nasional/JKN). The current aim of the study was to improve the usefulness of future economic evaluation for resource allocation by appraising current methodology, reporting, and source of evidence quality of studies. Methods: The inclusion and exclusion criteria were applied to search for relevant studies using a systematic review. The methodology and reporting adherence were appraised according to Indonesia's HTA Guideline issued in 2017. The differences in adherence before and after the guideline dissemination were compared using Chi-square and Fisher's exact tests for methodology adherence wherever appropriate, and the Mann-Whitney test for reporting adherence. The source of evidence quality was assessed using evidence hierarchy. Two scenarios of the study start date and the guideline dissemination period were tested using sensitivity analyses. Findings: Eighty-four studies were obtained from PubMed, Embase, Ovid, and two local journals. Only two articles cited the guideline. No statistically significant difference (P > 0.05) was found between the pre-dissemination and post-dissemination period with respect to methodology adherence, except for outcome choice. Studies during the post-dissemination period showed a higher score for reporting which was statistically significant (P = 0.01). However, the sensitivity analyses revealed no statistically significant difference (P > 0.05) in methodology (except for modelling type, P = 0.03) and reporting adherence between the two periods. Interpretation: The guideline did not impact the methodology and reporting standard used in the included studies. Recommendations were provided to improve the usefulness of economic evaluations for Indonesia. Funding: The Access and Delivery Partnership (ADP) hosted by the United Nations Development Programme (UNDP) and the Health Systems Research Institute (HSRI).

The physical activity at work (PAW) study: a cluster randomised trial of a multicomponent short-break intervention to reduce sitting time and increase physical activity among office workers in Thailand.

Background: Sedentary behaviour increases the risks of non-communicable diseases. The objective of this trial was to evaluate the effect of the Physical Activity at Work multicomponent intervention to reduce sedentary behaviour in Thai office workers. Methods: Offices under the Ministry of Public Health Thailand, were randomly allocated to the intervention and control group in a 1:1 ratio, stratified by office size. The intervention included individual (pedometer and lottery-based financial incentives), social (group movement breaks), environmental (posters), and organisational (leader encouragement) components. At baseline and 6-month follow-up, participants wore ActiGraphTM on the waist for ten days. The primary outcome was the between-group difference in sedentary time at 6-month, analysed using a linear mixed-effects model. Other outcomes were physical activity, biomarkers, productivity, and musculoskeletal health. Trial registration: The PAW study was registered at the Thai Clinical Trials Registry (ID TCTR20200604007) on 02 June 2020. Findings: 282 office workers were recruited and randomly allocated to the control group (142 participants, nine offices) and the intervention group (140 participants, nine offices). The mean age was 38.6 years (SD = 10.4), and 81% were women. There was no evidence of intervention effects on sedentary time during waking hours (-26.8; 95% CI = -69.2 to 15.7 min), physical activity levels, or biomarkers between groups at 6-month. In the adjusted analysis, increases in time spent in moderate-to-vigorous physical activity (5.45; 95% CI = -0.15 to 11.1 min) and step count (718; 95% CI = -45 to 1481 steps) during waking hours were observed, although there was no evidence of a difference between groups. Interpretation: The intervention did not significantly reduce sedentary time in Thai office workers. Suboptimal intervention uptake due to Covid-19 pandemic restrictions and loss of statistical power associated with recruitment constraints may explain this result. Further investigations are needed to evaluate the processes of the trial. Funding: The Thai Health Promotion Foundation and the International Decision Support Initiative (iDSI).

Evaluating the Value for Money of Precision Medicine from Early Cycle to Market Access: A Comprehensive Review of Approaches and Challenges.

OBJECTIVES: This study aimed to perform a comprehensive review of modeling approaches and methodological and policy challenges in the economic evaluation (EE) of precision medicine (PM) across clinical stages. METHODS: First, a systematic review was performed to assess the approaches of EEs in the past 10 years. Next, a targeted review of methodological articles was conducted for methodological and policy challenges in performing EEs of PM. All findings were synthesized into a structured framework that focused on patient population, Intervention, Comparator, Outcome, Time, Equity and ethics, Adaptability and Modeling aspects, named the "PICOTEAM" framework. Finally, a stakeholder consultation was conducted to understand the major determinants of decision making in PM investment. RESULTS: In 39 methodological articles, we identified major challenges to the EE of PM. These challenges include that PM applications involve complex and evolving clinical decision space, that clinical evidence is sparse because of small subgroups and complex pathways in PM settings, a one-time PM application may have lifetime or intergenerational impacts but long-term evidence is often unavailable, and that equity and ethics concerns are exceptional. In 275 EEs of PM, current approaches did not sufficiently capture the value of PM compared with targeted therapies, nor did they differentiate Early EEs from Conventional EEs. Finally, policy makers perceived the budget impact, cost savings, and cost-effectiveness of PM as the most important determinants in decision making. CONCLUSIONS: There is an urgent need to modify existing guidelines or develop a new reference case that fits into the new healthcare paradigm of PM to guide decision making in research and development and market access.

What are economic costs and when should they be used in health economic studies?

Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources' opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource's value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.