PharmacoEconomics最新文献

Background: Multistate models have been widely applied in health technology assessment. However, extrapolating survival in a multistate model setting presents challenges in terms of precision and bias. In this article, we develop an individual-level continuous-time multistate model that integrates relative survival extrapolation and mixed time scales.

Methods: We illustrate our proposed model using an illness-death model. We model the transition rates using flexible parametric models. We update the hesim package and the microsimulation package in R to simulate event times from models with mixed time scales. This feature allows us to incorporate relative survival extrapolation in a multistate setting. We compare several multistate settings with different parametric models (standard vs. flexible parametric models), and survival frameworks (all-cause vs. relative survival framework) using a previous clinical trial as an illustrative example.

Results: Our proposed approach allows relative survival extrapolation to be carried out in a multistate model. In the example case study, the results agreed better with the observed data than did the commonly applied approach using standard parametric models within an all-cause survival framework.

Conclusions: We introduce a multistate model that uses flexible parametric models and integrates relative survival extrapolation with mixed time scales. It provides an alternative to combine short-term trial data with long-term external data within a multistate model context in health technology assessment.

Background and objectives: Disorders of gut-brain interaction are highly prevalent and burdensome conditions for both patients and healthcare systems. Given the limited effectiveness of pharmacotherapy in treating disorders of gut-brain interaction, non-pharmacological interventions are increasingly used; however, the value for money of non-pharmacological treatments is uncertain. This is the first review to assess the economic evaluation evidence of non-pharmacological interventions for disorders of gut-brain interaction.

Methods: A scoping review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Reporting adhered to ISPOR's good practices for systematic reviews with cost and cost-effectiveness outcomes. Comprehensive searches were performed on 24 October, 2023, and an updated search was run on 18 May, 2024 in PubMed/MEDLINE, Embase, Web of Science, Scopus and the International HTA database, with two reviewers screening studies in parallel. The novel Criteria for Health Economic Quality Evaluation (CHEQUE) framework was used to assess methodological and reporting quality. Reporting quality was further assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022.

Results: Fifteen studies were included. Most studies examined treatments for irritable bowel syndrome. Cognitive behavioural therapy, dietary interventions and sacral neuromodulation were cost effective. Acupuncture and physiotherapy were not. CHEQUE assessment showed 12 studies met at least 70% of the methodological criteria, and 14 studies achieved 70% or more for reporting quality.

Conclusions: This review highlights gaps in the current evidence base, particularly in the robustness and generalisability of results due to methodological inconsistencies. Future research should incorporate longer follow-ups, comprehensive cost assessments, subgroup analyses, equity considerations and clearer justifications for modelling assumptions.

Objective: Health technology assessment is used extensively by the Pharmaceutical Benefits Advisory Committee (PBAC) to inform medicine funding recommendations in Australia. The PBAC often does not recommend medicines due to uncertainties in economic modelling that result in delaying access to medicines for patients. The systematic identification of which uncertainties can be reduced with alternative evidence or the collection of additional data can help inform recommendations. This study aims to characterise different types of uncertainty in economic models and empirically assess their association with the PBAC recommendations.

Methods: A framework was developed to characterise four types of uncertainties: methodological, structural, generalisability and parameter uncertainty. The first two types were further subcategorised into parameterisable and unparameterisable uncertainty. Data on uncertainty and other factors were extracted from PBAC's Public Summary Documents of first submissions for 193 medicine (vaccine)-indication pairs including economic modelling between 2014 and 2021. Logistic regression was used to estimate the average marginal effect of each type of uncertainty on the probability of a positive recommendation.

Results: The PBAC more often raised issues regarding parameter uncertainty (95%) and parameterisable structural uncertainty (83%) than generalisability uncertainty (48%) and unparameterisable methodological uncertainty (56%). The logistic regression results suggested that the PBAC was more likely to recommend a medicine without unparameterisable methodological, generalisability, and parameterisable structural uncertainty by 15.0%, 10.2 %, and 17.6%, respectively. Parameterisable methodological, unparameterisable structural and parameter uncertainty were not significantly associated with the PBAC recommendations.

Conclusions: This study identified the uncertainties that had significant associations with PBAC recommendations based on the first submission. This may help improve model quality and reduce resubmissions in the future, thus improving patients' access to medicines.

Background: Treating unresectable hepatocellular carcinoma (uHCC) is challenging. Clinical trials have shown that Single Tremelimumab Regular Interval Durvalumab (STRIDE) offers clinical benefits as a first-line treatment for uHCC, but its cost effectiveness remains unknown in the USA.

Objective: We aimed to assess the cost effectiveness of STRIDE (tremelimumab plus durvalumab) versus sorafenib and durvalumab monotherapy as the first-line treatment for uHCC in the USA.

Methods: A partitioned survival model was constructed to assess the cost effectiveness of STRIDE compared to sorafenib and durvalumab monotherapy as the first-line treatment for uHCC from the US societal perspective. The time horizon was 48 months with 1-month cycles. Seven parametric survival functions replicated survival curves from clinical trials, with the best-fitting model used to calculate survival probabilities. Costs, health utilities, and adverse events were included, with quality-adjusted life-years (QALYs) as the primary effectiveness measure. Both costs and effectiveness were discounted at 3%. In the base-case analysis, the incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $150,000 per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to examine the uncertainty of the model.

Results: In the base-case analysis, STRIDE was cost effective compared to sorafenib, with an incremental cost-effectiveness ratio of $97,995.51 per QALY gained, based on a willingness-to-pay threshold of $150,000 per QALY gained. However, STRIDE was not cost effective compared to durvalumab monotherapy at the same threshold, with an incremental cost-effectiveness ratio of $754,408.92 per QALY gained. Deterministic sensitivity analyses were consistent with the base-case analysis. A probabilistic sensitivity analysis indicated that STRIDE was more likely to be cost effective than sorafenib and durvalumab monotherapy when the willingness-to-pay exceeded $101,000 and $713,000, respectively.

Conclusions: The STRIDE regimen appears to be cost effective compared to sorafenib but not compared to durvalumab for first-line uHCC treatment in the USA. However, durvalumab has not yet been approved for uHCC in the USA. Future research should focus on long-term data and economic evaluations of other recommended biologics.

Background: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs.

Methods: We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors.

Findings: A total of 105 studies spanning 2002-2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61%), with 17 non-GBD studies additionally referenced, along with primary derivation. Inconsistencies in the utilisation of weights were evident: of the 100 usages of GBD-sourced weights, only in 47 instances (47%) had the weight value been explicitly specified with an appropriate up-to-date reference cited (constituting 28% of all weight usages, 47/165). Sensitivity analyses on weight values had been conducted in 30% of studies (31/105). Twelve studies did not clearly specify weights or their sources; nine further calculated DALYs without morbidity. The review suggests methodological gaps in current approaches for representing important aspects of TB, including TB-HIV coinfection, treatment, drug-resistance, extrapulmonary TB and psychological impacts. We propose a set of best practice recommendations.

Interpretation: There is a need for increased rigour in the application, sensitivity testing and reporting of TB disability weights. Furthermore, there appears a desire among researchers to reflect elements of the tuberculosis experience beyond those allowed for by GBD disability weights.

Background: People's time is a finite resource and a valuable input that ought to be considered in economic evaluations taking a broad, societal perspective. Yet, evaluations of interventions focusing on children and young people (CYP) rarely account for the opportunity cost of time in this population. As a key reason for this, health economists have pointed to uncertainty around when it is appropriate to include CYP time-related costs in an economic evaluation and highlighted the lack of clear guidance on the topic.

Methods: With this in mind, we carried out a Delphi study to establish a list of relevant considerations for researchers to utilise whilst making decisions about whether and when to include CYP time in their economic evaluations. Delphi panellists were asked to propose and rate a set of possible considerations and provide additional thoughts on their ratings. Ratings were summarised using descriptive statistics, and text comments were interrogated through thematic analysis.

Findings: A total of 73 panellists across 16 countries completed both rounds of a two-round Delphi study. Panellists' ratings showed that, when thinking about whether to include displaced CYP time in an economic evaluation, it is very important to consider whether: (1) inclusion would be in line with specified perspective(s) (median score: 9), (2) CYP's time may already be accounted for in other parts of the evaluation (median score: 8), (3) the amount of forgone time is substantial, either in absolute or relative terms (median score: 7) and (4) inclusion of CYP's time costs would be of interest to decision-makers (median score: 7). Respondents thought that considerations such as (1) whether inclusion would be of interest to the research community (median score: 6), (2) whether CYP's time displaced by receiving treatment is 'school' or 'play' time (median score: 5), and (3) whether CYP's are old enough for their time to be considered valuable (median score: 5) are moderately important. A range of views was offered to support beliefs and ratings, many of which were underpinned by compelling normative questions.

Objectives: Published literature has levied criticism against the cost-minimisation analysis (CMA) approach to economic evaluation over the past two decades, with multiple papers declaring its 'death'. However, since introducing the requirements for economic evaluations as part of health technology (HTA) decision-making in 1992, the cost-minimisation analysis (CMA) approach has been widely used to inform recommendations about the public subsidy of medicines in Australia. This research aimed to highlight the breadth of use of CMA in Australia and assess the influence of preconditions for the approach on subsidy recommendations METHODS: Relevant information was extracted from Public Summary Documents of Pharmaceutical Benefits Advisory Committee (PBAC) meetings in Australia considering submissions for the subsidy of medicines that included a CMA and were assessed between July 2005 and December 2022. A generalised linear model was used to explore the relationship between whether medicines were recommended and variables that reflected the primary preconditions for using CMA set out in the published PBAC Methodology Guidelines. Other control variables were selected through the Bolasso Method. Subgroup analysis was undertaken which replicated this modelling process.

Results: While the potential for inferior safety or efficacy reduced the likelihood of recommendation (p < 0.01), the effect sizes suggest that the requirements for CMA were not requisite for recommendation.

Conclusion: The Australian practice of CMA does not strictly align with the PBAC Methodology Guidelines and the theoretically appropriate application of CMA. However, within the confines of a deliberative HTA decision-making process that balances values and judgement with available evidence, this may be considered acceptable, particularly if stakeholders consider the current approach delivers sufficient clarity of process and enables patients to access medicines at an affordable cost.

Objectives: The objective of this study is to compare different information retrieval methods that can be used to identify utility inputs for health economic models.

Methods: The usual practice of using systematic review methods was compared with two alternatives (iterative searching and rapid review), using a health technology assessment (HTA) case study in ulcerative colitis (UC). We analysed whether there were differences in the utility values identified when using the alternative search methods. Success was evaluated in terms of time, burden and relevance of identified information. The identified utility values were tested in an executable health economic model developed for UC, and the model results were compared.

Results: The usual practice of using systematic review search approaches identified the most publications but was also the least precise method and took longest to complete. The inclusion of data from the different search methods in the model did not lead to different conclusions across search methods.

Conclusions: In this case study, usual practice was less efficient and resulted in the same health economic model conclusions as the alternative search methods. Further case studies are required to examine whether this conclusion might be generalisable.

Treatment effect waning (TEW) refers to the attenuation of treatment effects over time. Assumptions of a sustained immuno-oncologic treatment effect have been a source of contention in health technology assessment (HTA). We review how TEW has been addressed in HTA and in the wider scientific literature. We analysed company submissions to English language HTA agencies and summarised methods and assumptions used. We subsequently reviewed TEW-related work in the ISPOR Scientific Presentations Database and conducted a targeted literature review (TLR) for evidence of the maintenance of immuno-oncology (IO) treatment effects post-treatment discontinuation. We found no standardised approach adopted by companies in submissions to HTA agencies, with immediate TEW most used in scenario analyses. Independently fitted survival models do however suggest TEW may often be implicitly modelled. Materials in the ISPOR scientific database suggest gradual TEW is more plausible than immediate TEW. The TLR uncovered evidence of durable survival in patients treated with IOs but no evidence that directly addresses the presence or absence of TEW. Our HTA review shows the need for a consistent and appropriate implementation of TEW in oncology appraisals. However, the TLR highlights the absence of direct evidence on TEW in literature, as TEW is defined in terms of relative treatment effects-not absolute survival. We propose a sequence of steps for analysts to use when assessing whether a TEW scenario is necessary and appropriate to present in appraisals of IOs.